107年會

Agenda

Contents Floor Plan of Conference Rooms ........................................................................................... 2 Daily Program Schedule........................................................................................................... 5 Opening Remarks ...................................................................................................................... 7 Board of Directors ...................................................................................................................... 9 Sponsors ................................................................................................................................... 10 Hnorary Guests .........................................................................................................................11 Agenda ...................................................................................................................................... 34 Abstract PL：Plenary Lecture (1-4) ................................................................................................. 52 DAROC-TADE：DAROC-TADE Joint Symposium....................................................... 58 MTP：Meet the Professor (1-2) ......................................................................................... 65 SE：Symposium-Endocrine (1-6)...................................................................................... 67 SD：Symposium-Diabetes (1-6) ........................................................................................ 90 YL：Young Investigator Research Lecture ...................................................................... 104 AP：2018 Award .............................................................................................................. 109 OE：Oral Presentation-Endocrine (1-6) .......................................................................... 113 OD：Oral Presentation-Diabetes (1-6) ............................................................................ 119 PE：Poster Presentation-Endocrine (1-29) ...................................................................... 125 PD：Poster presentation- Diabetes (1-27) .................................................................... 158 BP：Exhibitor poster display (1-3) .................................................................................. 187

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39th Annual Meeting of The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan) Date: 10-11 March 2018 Venue: NTUH International Convention Center

Program March 10, 2018 (Saturday) Conference Room 101

Conference Room 301

Conference Room 402AB

Conference Room 402CD

Conference Room 202

Conference Room 203

LS-5 Novo Nordisk

LS-6 Pfizer

DAROC-TADE DAROC-TADE Joint Symposium

8:00-12:00

12:00-13:00

Conference Room 401

LS-1 Novartis (Taiwan)

MTP-1 Meet the Professor-1

LS-2 Eli Lilly Company (Taiwan)

LS-3 Novartis (Taiwan)

LS-4 AstraZeneca

13:20-13:30

Opening (Room 101)

13:30-14:15

Plenary Lecture-1 (Conference Room 101)

14:15-15:00

Plenary Lecture-2 (Conference Room 101)

15:00-15:20

Break (Poster Stand -3 Floor Walkway)

SE-1

SD-1

YL

SE-2

15:20-17:00

ESROC and KES DM and Geriatric Young New Progress in Joint Symposium Syndrome: Muscle Investigator Treatment and and Brain Research Diagnosis of Lecture Thyroid Diseases

17:00-18:00

Oral Oral Presentaion(DM) Presentaion(EN)

OD

18:00-21:00

OE

MTP-2 Meet the Professor-2

Welcome Dinner (Conference Room 101)

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March 11, 2018 (Sunday) Conference Room 101 SD-2 2018 DAROC Clinical Practice 08:00-09:30 Guidelines for Diabetes Care

Conference Room 301 SD-3 Clinical Management in Diabetes

Conference Room 401

Conference Room 402AB

Conference Conference Conference Room 402CD Room 202 Room 203

SE-3 SE-4 SD-4 Joint Symposium Thyroid Basic Research with Taiwan Nodules and in Diabetes and Society of Differentiated Endocrinology Aldosteronism Carcinoma Clinical Manual

09:30-09:45

Break (Poster Stand -3 Floor Walkway)

09:45-10:30

Plenary Lecture-3 (Conference Room 101)

10:30-12:00

General Assembly (Conference Room 101)

12:00-12:10

Group Picture (1st Floor Square)

12:10-13:20

LS-7

LS-8

LS-9

LS-10

LS-11

LS-12

LS-13

Medtronic

Boehringer Ingelheim / Lilly

Sanofi

MSD

Astellas

Abbott

Orient Euro Pharma

13:30-14:15

Plenary Lecture-4 (Conference Room 101)

14:15-14:45

Break (Poster Stand -3 Floor Walkway)

SD-5 SD-6 SE-5 Pheochromocytoma Diabetes Diabetes and and Nervous Kidney: from 14:45-16:25 System: Brain Diabetologist's and and Peripheral Nephrologist's View Nerves

16:25-16:30

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SE-6

AP

Lipid Forum

2018 Award Grant Award Lectures

Closing

Agenda

理事長致詞 歡迎各位會員參加 107 年的內分泌暨糖尿病學會年會及學術研討會。本年度大 會由內分泌學會主辦，內容豐富完整。內分泌學會邀請國際知名的 Professor Rossella Elisei 及林仁德教授擔任 Plenary lecture、Meet-the-Professor，兩位教授的學術涵養及臨 床經驗豐富，會員們可以由他們的演講中有很好的學習。內分泌學會安排的研討會共 有六場，分別以甲狀腺眼病變 ( 與韓國內分泌學會交流 )、甲狀腺疾病診治新發展、原 發性醛酮症 ( 與台灣皮質醛酮症學會合辦 )、甲狀腺結節與甲狀腺癌處置 ( 學會出版的 「甲狀腺結節及分化型癌臨床手冊」新書發表 )、嗜鉻細胞瘤、血脂代謝等為主題，所 邀請的演講者及主持人都是首屈一指的專家，內容精彩可期。另外，糖尿病學會安排 的 Plenary lecture 及 symposium、論文獎得獎演講、會員的口頭或壁報論文報告、藥界 同仁安排的 Lunch symposium 等也都是精采萬分，相信所有的會員都能夠在這場學術 盛宴中收穫滿滿。 謹此感謝所有主持人及演講者、內分泌學會劉鳳炫秘書長、蘇登煌、邱偉益及吳 婉禎副秘書長、黃璿如及蘇心榆秘書、糖尿病學會許惠恒理事長、林時逸秘書長及秘 書處同仁、所有的贊助者，更謝謝所有會員的參予與支持。謹祝 大家身體健康，萬事 如意。

社團法人中華民國內分泌學會

曾芬郁

理事長

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理事長致詞 各位會員女士、先生： 歡迎各位會員女士先生參加中華民國內分泌暨糖尿病學會第 13 屆第 3 次會員大會！ 每年我們都期待相聚在此，透過年會的機會，與國內外專家學者零距離的討論、分享經 驗，以期會員能獲得更多更新的醫療知識及技術，應用到臨床病人照護，並擴展國際視 野。 本會為國際糖尿病聯盟 (IDF) 的會員國之一，每年 11 月份本會舉辦聯合國世界糖尿 病日活動，除了有園遊會、點燈等活動，無不精彩呈現台灣對糖尿病照護的努力與重視。 在去年 (2017) 與苗栗政府衛生局合辦於苗北藝文中心點燈，共吸引 2,000 人參與，提升 民眾對糖尿病的重視。 而去年籌備編輯了一整年的指引改版工作，亦將於今年年會出版「2018 糖尿病臨床 照護指引」，會員們可以上網下載相關資料，期待將最新的糖尿病相關領域的知識、研 究帶給會員。 今年年會的糖尿病節目中，我們特別安排各糖尿病相關熱門領域的議題，將各領域 的新進展呈現給會員，包括： DM and Geriatric syndrome: Muscle and Brain 研討會、2018 DAROC Clinical Practice Guidelines for Diabetes Care、Clinical Management in Diabetes、Basic Research in Diabetes and Endocrinology、Diabetes and Nervous System: Brain and Peripheral Nerves、與腎臟學會合辦之 Diabetes and Kidney: From Diabetologist´s and Nephrologist´s view、與衛教學會合辦衛教課程研討會、研究計畫獎勵成果發表。邀請各領域的專家學 者、節目豐富精彩，定能獲益良多。此外，會員論文投稿共計有 68 篇，口頭報告 12 篇、 壁報展示 56 篇。 感謝所有會員女士先生以及貴賓參加本學會與內分泌學會之年度盛會。祝大家身體 健康，平安快樂，大會圓滿成功。 社團法人中華民國糖尿病學會 理事長 謹上 107 年 3 月 10 日

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Agenda

Board of Directors

（依照姓氏筆劃排序）

The Endocrine Society of the Republic of China(Taiwan) President

曾芬郁 Fen-Yu Tseng

Standing Executive Board

王佩文 Pei-Wen Wang

蔡克嵩 Keh-Sung Tsai

Executive Board

王治元 Chih-Yuan Wang 李亭儀 Annie Lee 張慶忠 Ching-Chung Chang 陳思達 Szu-Tah Chen

陳涵栩 Harn-Shen Chen 黃天祥 Tien-Shang Huang 葉振聲 Tjin-Shing Jap 簡銘男 Ming-Nan Chien

Standing Control Board

林仁德 Jen-Der Lin

Control Board

林宏達 Hong-Da Lin

Secretary General

劉鳳炫 Feng Hsuan Liu

Deputy Secretary General

吳婉禎 Wan-Chen Wu 蘇登煌 Deng-Huang Su

張天鈞 Tien-Chun Chang

邱偉益 Wei-Yih Chiu

The Diabetes Association of the Republic of China(Taiwan) President

許惠恒 Wayne Huey-Herng Sheu

Standing Executive Board

辛錫璋 Shyi-Jang Shin

陳榮福 Jung-Fu Chen

Executive Board

杜思德 Shih-Te Tu 黃禹堯 Yu-Yao Huang 陳清助 Ching-Chu Chen 蔡世澤 Shih-Tzer Tsai

謝明家 Ming-Chia Hsieh 洪乙仁 Yi-Jen Hung 楊偉勛 Wei-Shiung Yang 黃建寧 Chien-Ning Huang

Standing Control Board

莊立民 Lee-Ming Chuang

Control Board

何橈通 Low-Tone Ho

Secretary General

林時逸 Shih-Yi Lin

Secretary

李弘元 Hung-Yuan Li 李奕德 I-Te Lee 李建興 Chien-Hsing Lee

戴東原 Tong-Yuan Tai

王俊興 Jun-Sing Wang 朱志勳 Chih-Hsun Chu 林昆德 Kun-Der Lin 9

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廠商贊助名單

（依照筆劃排序）

台灣禮來股份有限公司

Eli Lilly Company (Taiwan)

賽諾菲股份有限公司

Sanofi Taiwan Co. Ltd.

臺灣阿斯特捷利康股份有限公司

AstraZeneca Taiwan Limited

美敦力醫產品股份有限公司

Medtronic (Taiwan) Ltd.

美商默沙東藥廠股份有限公司台灣分公司

Merck Sharp

台灣諾華股份有限公司

Novartis (Taiwan) Co., Ltd.

台灣諾和諾德藥品股份有限公司

Novo Nordisk Pharma (Taiwan) Ltd.

台灣拜耳股份有限公司

Bayer Taiwan Co., Ltd.

台灣百靈佳殷格翰股份有限公司

Boehringer Ingelheim Taiwan Ltd.

台灣安斯泰來製藥股份有限公司

Astellas Pharma Taiwan, Inc.

台灣田邊製藥股份有限公司

Taiwan Tanabe Seiyaku Co., Ltd.

友華生技醫藥股份有限公司

Orient EuroPharma Co., Ltd.

力大圖書有限公司

The Leader Book Company Ltd.

輝瑞大藥廠股份有限公司

Pfizer Taiwan Ltd.

衛采製藥股份有限公司

Eisai Taiwan, Inc.

台灣安晟信有限公司

Ascensia Diabetes Care Taiwan, Ltd.

輝瑞生醫股份有限公司

Pfizer Limited Taiwan

裕利股份有限公司

Zuellig Pharma Holdings Pte. Ltd.

台灣安進藥品有限公司

Amgen Taiwan Ltd.

嘉德藥品企業股份有限公司

Char Deh Drugs Enterprise Co., Ltd.

法商益普生股份有限公司台灣分公司

IPSEN Pharma Taiwan Branch

美艾利爾健康股份有限公司

Alere Taiwan

台灣武田藥品工業股份有限公司

Takeda Pharmaceuticals Taiwan , Ltd.

安克生醫股份有限公司

AmCad BioMed Corporation

創益生技股份有限公司

Chuang Yi Biotech

10

Hnorary Guests

Rossella Elisei, M.D. PRESENT POSITION Associate Professor of Endocrinology at the Department of Clinical and Experimental Medicine, Endocrine Unit, University of Pisa, Pisa, Italy.

EDUCATION July 1977

April 3, 1985 July 9, 1988

Baccalaureate (Maturità Scientifica) (60/60), Liceo Scientifico F. Enriquez, Livorno, Italy M.D. degree (magna cum laude), University of Pisa, School of Medicine, Pisa, Italy Specialty degree in Endocrinology (magna cum laude), University of Pisa, Postgraduate School of Endocrinology, Pisa, Italy.

FOREIGN LANGUAGES Fluent knowledge of English and French Languages PROFESSIONAL EXPERIENCES January 1982-April 1985:

April 1985- December 1988:

January 1991-August 2001:

August 2001 to December 2008:

December 2008 to present:

Student fellow, Istituto di Endocrinologia, Metodologia Clinica e Medicina del Lavoro, University of Pisa, Pisa, Italy.

Medical Internship, Istituto di Endocrinologia, Metodologia Clinica e Medicina del Lavoro, University of Pisa, Pisa, Italy.

Funzionario Tecnico VIII livello (equivalent to Assistant Researcher), Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.

University Researcher at the Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.

Associate Professor of Endocrinology at the Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.

RESEARCH TRAINING AND EXPERIENCE IN FOREIGN INSTITUTIONS January 1989-December 1990: Postdoctoral Research Fellow at the I.R.I.B.H.N (Istitute

de Recherche Interdisciplinaire en Biologie Humaine et

Nucleaire), Endocrinology Branch, Université Libre de

Bruxelles (Free University of Bruxelles), Bruxelles, Belgium.

March 1995-June 1995: Postdoctoral Assistant, Division of Endocrinology, Cedars-Sinai

Medical Center/UCLA School of Medicine, Los Angeles, CA, USA. July 1995-June 1997: Postdoctoral Assistant, Division of Endocrinology and

Metabolism, University of Cincinnati, College of Medicine,

Cincinnati, OH, USA. January 1998 Active participation to the course “Current techniques in

radiation mutagenesis” at the Department of Radiation Genetics

and Chemical Mutagenesis, University of Leiden, Leiden,

The Netherlands.

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RESEARCH GRANTS 1989-1991 Grant from the Italian Public Education Ministry for International collaboration with I.R.I.B.H.N of Bruxelles, 1989. Mentor: Prof. J. Dumont and Prof. G. Vassart.

1990-1991 Grant from E.E.C (European Economic Community) for International collaboration with I.R.I.B.H.N of Bruxelles, 1990. Mentors: Prof. J. Dumont and Prof. G. Vassart.

2000 to the present: Research grants from Associazione Italiana per la Ricerca sul Cancro (Italian association for Cancer Research) 1999 to 2012: Research grants from Ministero della Università e della Ricerca Italiana (Italian Ministry of University and Research) 2006 to the present: Research grants from Istituto Toscano Tumori (Tuscan Institut of Tumors) PROFESSIONAL INTERNATIONAL AWARDS 2006: International award for excellence in published clinical research in the Journal of Clinical Endocrinology and Metabolism. Title of the awarded publication: Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.

Vol 91: 926-932.

2011: The ETA (European Thyroid Association) Max Pierre Konig Poster Award in recognition of the best poster in clinical thyroidology titled: Patients with DTC who underwent radioiodine remnant ablation with low activity of 131-I either with rhTSH or after LT4 withdrawal show the same outcome after 10 years follow up.

2011: “Light of Life Foundation” international award dedicated to the best thyroid cancer researcher of the year, Sloan Kettering Memorial Cancer Center di New York, February th 7 , 2012.

2012: International award for excellence in published clinical research in the Journal of Clinical Endocrinology and Metabolism. Title of the awarded publication: The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. Vol 97: 426-435.

CLINICAL TRIALS From 1997 up to 2005: subinvestigator in several clinical trials on drugs for thyroid cancer treatment among which: AMG706 on progressive, locally advanced or metastatic, radioiodine refractory (RAI-R) DTC and in medullary thyroid cancer (ClinicalTrials.gov identifier, NCT00121628) Axitinib in MTC and DTC (ClinicalTrials.gov identifier NCT00389441).

From 2005 to the present: Principal Investigator in several phase II/III clinical trials on drugs for thyroid cancer treatment and in particular in: Vandetanib in advanced medullary thyroid cancer (ZETA trial: ClinicalTrials.gov identifier NCT00410761) Cabozantinib in advanced medullary thyroid cancer (EXAM trial ClinicalTrials.gov identifier NCT01908426) Vandetanib in advanced and radiorefractory thyroid cancer (VERIFY trial: ClinicalTrials.gov identifier NCT01876784) 12

Hnorary Guests Sorafenib in dedifferentiated and radiorefractory thyroid cancer (DECISION trial (ClinicalTrials. gov identifier NCT00984282) Lenvatinib in dedifferentiated and radiorefractory thyroid cancer (SELECT trial: ClinicalTrials. gov identifier NCT01321554).

Vemurafenib in dedifferentiated and radiorefractory BRAF mutated thyroid cancer (ClinicalTrials. gov identifier NCT01286753) Selumetinib to increase radioiodine uptake (ASTRA trial: ClinicalTrials.gov identifier NCT01843062) Combretastatin in anaplastic thyroid cancer MEMBERSHIP IN PROFESSIONAL ASSOCIATIONS 1991-present Italian Society of Endocrinology, Ordinary Member.

1992-present European Thyroid Association, Ordinary Member.

1997-present European Thyroid Association Cancer Research Network, Ordinary Member.

1998-2003 Secretary of the European Thyroid Association Cancer Research Network.

2003-2008 President of the European Thyroid Association Cancer Research Network 2009-present Member of the Directors’ board of the International Thyroid Oncology Group 2012-2016 Member of the Executive Committee of the European Thyroid Association REVIEWER and JOURNALS’ BOARDS O 3 International Endocrine Meeting “Endocrinology Under 35”, September 1992: Scientific Program Committee, Abstract Reviewer and Chairperson of the Thyroid Cancer session.

Manuscripts reviewer for Thyroid, Journal of Clinical Endocrinology and Metabolism, Journal of Clinical Investigation, European Journal of Endocrinology, Clinical Endocrinology, many others.

Past member of the Editorial Board of Journal of Endocrinological Investigation (1997-2007), Endocrine Related Cancer (2008-2010); Journal of Clinical Endocrinology and Metabolism (20092011); Active member of the Editorial Board of Endocrine Review and of Thyroid journals.

MAIN TOPICS OF RESEARCH Humoral and tissue markers of differentiated, undifferentiated and medullary thyroid carcinomas. Autoimmunity and thyroid carcinoma.

Molecular biology studies of autoimmune thyroid diseases.

Oncogenes and growth factors of thyroid carcinomas. Target therapies in advanced thyroid cancer PUBLICATIONS Author of many publications including 166 papers in Peer-Reviewed Journals, 50 manuscripts in Proceedings of Meetings and Book Chapters and 300 Abstracts for National and International Meetings.

(I.F. totale 823,53; medio 4,96; mediano 4,79) (H Index 51, according to Scopus) Pisa, 15 May 2017

Rossella Elisei Associate Professor of Endocrinology

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Yutaka Seino, M.D., Ph.D. Personal Information Date of Birth:November, 7, 1941 Nationality: Japan School Attended Kyoto University School of Medicine, Kyoto, Japan from April, 1963 to March, 1967 Employment President, Kansai Electric Power Hospital, Osaka Director General, Kansai Electric Power Medical Research Institute Emeritus Professor of Kyoto University,Kyoto Professional Affiliations Chair, Asian Association for the Study of Diabetes(AASD) Chair, The Japan Association for Diabetes Education and Care Chair, The Japan Society of Metabolism and Clinical Nutrition Research Field Islet cell physiology Physiology and pathophysiology of incretin Clinical nutrition and metabolism More than 600 publications in English ( original and review ) articles Awards IDF Education and Integrated Care Award 2017 ADA Harold Rifkin Award for Distinguished International Service in the Cause of Diabetes 2016 Endocrine Society (USA) 2014 International Excellence in Endocrinology Award IDF Regional Award 2014 Erwin von Bälz Prize 2013 Novartis Prize in Diabetes Long-standing Achievement 2009 Medical Award for The Japan Medical Association 2013 Aglaia Award for Japanese society of Metabolism and Clinical Nutrition 2012 Hagedon Award for Japan Diabetes Society 1998 Society Award for Japanese Society of Nutrition and Food Science 1999 Saiki Award for Japanese Society of Nutrition and Food Science 2007 Distinguished Investigator Award for the Japan Society of Diabetic Complications 2008 Goto Award for Japanese Society of Experimental Diabetes and Obesity 2010 IDF Lifetime Achievement Award 2017

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Hnorary Guests

Jen-der Lin, M.D. Personal Information Nationality: Taiwan, R.O.C. Position: Attending Physician Department: D ivision of Endocrinology & Metabolism, Department of Internal Medicine Organization: C hang Gung Memorial Hospital, Linkou Chang Gung University Email: einjd@adm.cgmh.org.tw Educational background & professional experience 2000 July – present Division of Endocrinology & Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital Professor in Medicine July 1990 - Dec. 1991 University of California, Los Angeles Research Fellow July 1983 - June 1985 Division of Endocrinology & Metabolism, Chang Gung Memorial Hospital, Taipei. Fellow Research Interests 1. Thyroid cancer 2. Protein purification 3. Thyroid cancer cell culture Publications 1 Circulating epithelial cell counts for monitoring the therapeutic outcome of papillary thyroid carcinoma. Oncotarget Vol. 8, (No. 44), pp: 77453-77464, 2017.

2 Long-term follow-up of papillary and follicular thyroid carcinomas with bone metastasis. PLoS One Mar. 9;12(3):e0173354. doi: 10.1371/journal.pone.0173354, 2017.

3 Higher Body weight and distant metastasis are associated with higher radiation exposure to the household environment from patients with thyroid cancer after radioactive iodine therapy. Medicine 2017 Sep;96(35):e7942.

4 Early recurrence papillary and follicular thyroid carcinoma predicts a worse outcome. Thyroid 19:1053-8, 2009.

5 Diagnosis and therapeutic strategy of papillary thyroid microcarcinoma. Arch Surg 140:940-5, 2005.

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Huey-Kang Sytwu, M.D., Ph.D. Personal Information Nationality: R.O.C. Position: Vice President and Distinguished Investigator Department: National Institute of Infectious Diseases and Vaccinology Organization: National Health Research Institutes Email: sytwu@nhri.org.tw Educational background & professional experience 1987 Medicine, National Defense Medical Center, Taipei, MD

Taiwan, R.O.C. 1997 Microbiology and Immunology, School of Medicine, PhD

Stanford University, U.S.A. 2000-present Chinese Society of Immunology, R.O.C. Board Director 2004-present Department of Microbiology and Immunology, Professor

National Defense Medical Center, Taipei, Taiwan, R.O.C. 2004-2006 Department of Biomedical Engineering, Professor and

National Defense Medical Center, Taipei, Taiwan, R.O.C. Chairman 2005-2009 Graduate Institute of Medical Sciences, Professor and Chairman

National Defense Medical Center, Taipei, Taiwan, R.O.C. 2007-2009 Department of Medical Research, Director

Tri-Service General Hospital, Taipei, Taiwan, R.O.C 2008-2009 Department of Medical Research, Director

National Defense Medical Center, Taipei, Taiwan, R.O.C 2009-2011 Graduate Institute of Life Sciences, National Defense Executive Commissioner

Medical Center and Academia Sinica, Taipei, Taiwan, R.O.C. 2009-2011 National Defense Medical Center, Taipei, Taiwan, R.O.C. Executive Dean 2011-2013 Medical Planning Division, Medical Affairs Bureau, Director

Ministry of National Defense, Taipei, Taiwan, R.O.C. 2011-present

National Research Program for Biopharmaceuticals, Council Member

Ministry of Science and Technology, R.O.C. 2013-2018 National Defense Medical Center, Taipei, Taiwan, R.O.C. President 2013-2018 Graduate Institute of Life Sciences, National Defense Director

Medical Center and Academia Sinica, Taipei, Taiwan, R.O.C. 2013-present National Examination of Physician and Dentist, Advisory Board Member

Ministry of Examination, R.O.C. 2014-present Chinese Society of Cell and Molecular Biology, R.O.C. Board Director 2014-present Taiwan Biobank, R.O.C. Advisory Council Member 2015-present Taiwan Medical Accreditation Council, R.O.C. Council Member 2015-present National Health Research Institutes, R.O.C. Academic Advisory Council Member 2015-present Medical Education Council, Ministry of Education, R.O.C. Advisory Board Member 2018-present National Institute of Infectious Diseases and Vaccinology, NHRI Distinguished Investigator 2018-present National Health Research Institutes Vice President

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Hnorary Guests Research Interests (Major) 1. Immunopathogenesis of autoimmune diseases 2. Preventive and therapeutic strategies for autoimmune diseases 3. Gene Manipulation Publications (5 important publications – latest sequence) 1 Divakar Kulshrestha, Yeh, L.-T., Chien, M.-W., Chou, F.-C., *Sytwu, H.-K. (2017) Peripheral autoimmune regulator induces exhaustion of CD4+ and CD8+ effector T cells to attenuate autoimmune diabetes in NOD mice. Frontiers in Immunology 8:1128-40.

2 Chien, M.-W., Lin, M.-H., Huang, S.-H., Fu, S.-H., Hsu, C.-Y., Yen, B.-L., Chen, J.-T., Chang, D.M., *Sytwu, H.-K.(2015) Glucosamine modulates T cell differentiation through downregulating N-linked glycosylation of CD25. The Journal of Biological Chemistry. 290:29329-29344.

3 Fu, S.-H., Lin, M.-H., Yeh, L.-T., Wang, Y.-L., Lin, S.-H., Chang, D.-M., *Sytwu, H.-K. (2015) Targeting tumor necrosis factor receptor 1 assembly reverses Th17-mediated colitis through boosting a Th2 response. Gut 64:765-775.

4 Yeh, L.-T., Maiw, S.-C., Lin, M.-H., Chou, F.-C., Shieh, S.-J., Chuang, Y.-P., Lin, S.-H., Chang, D.-M., *Sytwu, H.-K.(2013) Different modulation of Ptpn22 on effector and regulatory T cells leads to attenuation of autoimmune diabetes in transgenic non-obese diabetic mice. Journal of Immunology 191:594-607.

5 Sung, H.-H., Juang, J.-H., Lin, Y.-C., Kuo, C.-H., Hung, J.-T., Chen, A., Chang, D.-M., Chang, S.-Y., Hsieh, S.-L., *Sytwu, H.-K. (2004) Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in non-obese diabetic mice. Journal of Experimental Medicine 199:1143-1151.

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Abe Masanori, M.D., Ph.D. NIHON UNIVERSITY’s School of Medicine Department of Medicine Professor Abe Masanori Birth:1971 Nihon University Faculty of Medicine 1997 Graduated Domestic Kidney internal medicine Research keywords (Number of the published data : 5) 慢性腎臓病 高血圧 糖尿病性腎症 血液浄化療法 腹膜透析 Bibliography (Number of the published data : 18) 慢性腎臓病の降圧治療戦略 降圧薬の組み合わせで臨床効果に違いがあるか Medical Tribune 2009/12 臨床透析ハンドブック . 中毒治療における透析と血液吸着の使用 メディカル・サイエ ンス・インターナショナル 2009/10 臨床透析ハンドブック . 血漿交換療法（プラズマフェレシス）メディカル・サイエンス・ インターナショナル 2009/10 臨床透析ハンドブック . 緩徐持続的療法 メディカル・サイエンス・インターナショナ ル 2009/10 多臓器不全の治療 .( 社 ) 日本透析医学会 専門医試験問題解説集 ( 改訂第 6 版 )( 社 ) 日本透析医学会 2009/06 Papers (Number of the published data : 137) Haemodialysis-induced hypoglycaemia and glycaemic disarrays. Nature Reviews Nephrology 2015 Urinary ACE2 is associated with urinary L-FABP and albuminuria in patients with chronic kidney disease. Scadinavian Journal of Clinical and Laboratory Investigation 2015 Characterization of insulin adsorption behavior of dialyzer membranes used in hemodialysis Artificial Organs 2011 Antidiabetic agents in patients with chronic kidney disease and end-stage renal disease on dialysis: Metabolism and clinical practice. Current Drug Metabolism 2011 Benidipine reduces albuminuria and plasma aldosterone in mild to moderate stage chronic kidney disease with albuminuria. Hypertension Research 2011 ■ Research presentations (Number of the published data : 170) Oral presentation(general) インスリン治療中糖尿病透析患者は透析後高血糖が惹起される 18

Hnorary Guests 第 17 回日本糖尿病性腎症研究会 2004/12 Oral presentation(general) 血液浄化療法により救命し得たエダラボンによると思われる劇 症肝炎の一症例 第 50 回日本透析医学会総会 2005/06 Oral presentation(general) 糖尿病透析患者の血糖とインスリン濃度の変動 第 50 回日本 透析医学会総会 2005/06 Oral presentation(general) 糖尿病透 析患者では血液透析により血漿インスリンが 低下するため、透析後の高血糖が惹起される . 第 18 回日本糖尿病性腎症研究会 2006/10 Oral presentation(general) 糖尿病合併維持透析患者における血糖値および血清インスリン 濃度の変動 . 第 19 回日本糖尿病合併症学会 2004/10 日本糖尿病学会 日本急性血液浄化学会 日本循環器学会 日本腎臓学会 日本透析医学会

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Jeehee Yoon, M.D. Research Field Clinical endocrinology and metabolism Education / Training 2000-2006 Chonnam National University Medical School, Gwangju,

Korea 2007-2008 Intern at Chonnam National University Hospital, Gwangju,

Korea 2009-2012 Resident of internal medicine at Chonnam National University Hospital, Gwangju,

Korea 2009-2011 Master’s degree at Chonnam national University Graduate School, Gwangju, Korea 2013-2014 Clinical fellowship of endocrinology and metabolism at Chonnam National

University Hwasun Hospital, Korea Current Position Clinical assistant professor Short CV 2013-2014 Clinical fellowship of endocrinology and metabolism at Chonnam National

University Hwasun Hospital, Korea 2014.3~ Clinical assistant professor –Chonnam National University Bitgoeul Hospital,

Gwangju, Korea

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Mitsuhide Naruse, M.D., Ph.D. Special Research Fellow, Adrenal Project, Clinical Research Institute of Endocrinology and Metabolism, Kyoto Medical Center (KMC), National Hospital Organization (NHO), Japan ◆ Education/ Academic positions 1975 Graduated, Tohoku University School of Medicine/ National Board Medial Lisence 1976 Medical Internship, Tokyo Women’s Medical College 1977 Clinical Associate, Dept. of Medicine, Tokyo Women’s Medical College 1980 Research Associate, Dept. of Biochemistry (Dr. Inagami T), Vanderbilt Univ.(US) 1987 Instructor, Dept. of Medicine, Tokyo Women’s Medical University 1995 Associate Professor, Dept. of Medicine, Tokyo Women’s Medical University 2003 Chief, Division of Endocrinology, Clinical Res. Institute, National Kyoto Hospital 2008 Chief, Division of Endocrinology, Metabolism, and Hypertension, KMC, NHO 2011 Visiting Professor, Peking Union Medical College Hospital (China) 2012 Vice-Director, Clinical Res. Institute for Endocrinology and Metabolism, KMC 2016 Expert Supervisor, Medical Genome Center, National Center for Global Health

and Medicine (Tokyo, Japan) 2016 Present post, KMC, NHO ◆ Academic/Social activities Chair, Taskforce of Malignant Pheochromocytoma, Japan Endocrine Society Chair, Taskforce of Primary Aldosteronism, Japan Endocrine Society Member, Taskforce of Pheochromocytoma/Paraganglioma Clinical Guideline, Endocrine Soc. (US) President, 14th Japan Endocrine Pathology Meeting (2010, Kyoto) President, 4th International Symposium of Pheochromocytoma (2014, Kyoto) President, 1st East Asia Symposium of Rare Adrenal Diseases (2017, Tokyo) Ex-Director, Japan Endocrine Pathology Scientific Board member of European Network for the Study of Adrenal Tumors (ENS@T) Member: Japan Endocrine Society, Japan Society of Hypertension, Japan Society of Nephrology, Japan Diabetes Society, Endocrine Society (US) ◆ Specialties Medicine, Endocrinology and Metabolism, Adrenal diseases, Hypertension ◆ Principle Investigator Japan Pheochromocytoma Study (PHEO-J), Ministry of Health, Labor and Welfare Japan Primary Aldosteronism Study (JPAS), AMED Primary Hyperaldosteronism in Japan (PHAS-J) (RCT), National Hosp. Organization Clinical trial of Metirosine in PPGL (MCAP-J study) ◆ Awards Tokyo Women’s Medical University (2) Japan Endocrine Society (2) Japan Society of Hypertension (1) ◆ Publications 282 (English)/ 896 (Japanese) ◆ Presentation 349 (International), 1265 (Japanese) 21

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Masato Odawara, M.D., Ph.D. Curriculum Vitae

Affiliation: T he Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University Position: Director and Professor Email: odawara@tokyo-med.ac.jp Education/ Appointments 1980 Graduated School of Medicine and Faculty of Medicine, University of Tokyo. Medical Doctor 1999 Doctor of Philosophy(PhD), University of Tokyo 1990 Research Assistant, Tokyo University Hospital 1992 Lecturer, Institute of Clinical Medicine, University of Tsukuba 1996 Clinical Lecturer of Medicine, Oxford University 2000 Director, Division of Endocrinology and Metabolism, Department of Internal Medicine,

Toranomon Hospital, Federation of National Public Service Personnel Mutual Aid Associations 2004 Director and Professor of the Third Department of Internal Medicine,

Tokyo Medical University

Visiting Professor, Tokyo University of Pharmacy and Life Sciences 2009.9-2012.8 Executive Vice President of Tokyo Medical University Hospital 2014.4- Director and Professor of the Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University 2015 Executive Director of Japan Diabetes Foundation.

Director of a board of Japan Society of Adult Diseases

Director of a board of Japan Society of Diabetic Complications 2018.1 President of Japan Society of Adult Diseases Research Interests Research on genetic predisposition for the development of type 2 diabetes mellitus and diabetic microvascular and macrovascular complications.

Clinical trials on diabetic complications and treatment.

Brief List of Publications (Selected) 1. Ueki K, Sasako T, Okazaki Y, Kato M, Okahata S, Katsuyama H, Haraguchi M, Morita A, Ohashi K, Hara K, Morise A, Izumi K, Ishizuka N, Ohashi Y, Noda M, Kadowaki T; J-DOIT3 Study Group. : Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial.

Lancet Diabetes Endocrinol. 2017 Oct 24. pii: S2213-8587(17)30327-3.

2. Narisawa H, Komada Y, Miwa T, Shikuma J, Sakurai M, Odawara M, Inoue Y.: Prevalence, symptomatic features, and factors associated with sleep disturbance/insomnia in Japanese patients with type-2 diabetes. Neuropsychiatr Dis Treat. 2017 Jul 18;13:1873-1880.

3. Yamada H, Tanaka A, Kusunose K, Amano R, Matsuhisa M, Daida H, Ito M, Tsutsui H, Nanasato M, Kamiya H, Bando YK, Odawara M, Yoshida H, Murohara T, Sata M, Node K; PROLOGUE Study Investigators.: Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes: a subgroup analysis of the PROLOGUE study. Cardiovasc Diabetol. 2017 May 11;16(1):63.

4. Seki M, Kawai Y, Ishii C, Yamanaka T, Odawara M, Inazu M.: Functional analysis of choline transporters in rheumatoid arthritis synovial fibroblasts. Mod Rheumatol. 2017 Nov;27(6):995-1003.

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Hnorary Guests 5. Kozlovski P, Fonseca M, Mohan V, Lukashevich V, Odawara M, Paldánius PM, Kothny W.: Effect of race and ethnicity on vildagliptin efficacy: A pooled analysis of phase II and III studies.

Diabetes Obes Metab. 2017 Mar;19(3):429-435.

6. Shikuma J, Kan K, Ito R, Hara K, Sakai H, Miwa T, Kanazawa A, Odawara M.: Critical review of IgG4-related hypophysitis.

Pituitary. 2017 Apr;20(2):282-291.

7. Maruhashi T, Higashi Y, Kihara Y, Yamada H, Sata M, Ueda S, Odawara M, Terauchi Y, Dai K, Ohno J, Iida M, Sano H, Tomiyama H, Inoue T, Tanaka A, Murohara T, Node K; PROLOGUE Study Investigators.: Long-term effect of sitagliptin on endothelial function in type 2 diabetes: a subanalysis of the PROLOGUE study.

Cardiovasc Diabetol. 2016 Sep 13;15(1):134.

8. Sakai H, Nagao H, Sakurai M, Okumura T, Nagai Y, Shikuma J, Ito R, Imazu T, Miwa T, Odawara M. Correction: Correlation between Serum Levels of 3,3´,5´-Triiodothyronine and Thyroid Hormones Measured by Liquid Chromatography-Tandem Mass Spectrometry and Immunoassay.

PLoS One. 2016 Jul 7;11(7):e0159169.

9. Odawara M, Ishii H, Tajima N, Iwamoto Y.: Impact of patient attitudes and beliefs to insulin therapy upon initiation, and their attitudinal changes after initiation: the DAWN Japan study.

Curr Med Res Opin. 2016;32(4):681-6.

10. Odawara M, Miyagawa J, Iwamoto N, Takita Y, Imaoka T, Takamura T.: Once-weekly glucagonlike peptide-1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once-daily liraglutide in Japanese patients with type 2 diabetes: 52 weeks of treatment in a randomized phase III study.

Diabetes Obes Metab. 2016 Mar;18(3):249-57.

11. Hara K, Kadowaki T, Odawara M.: Genes associated with diabetes: potential for novel therapeutic targets? Expert Opin Ther Targets. 2016;20(3):255-67.

12. Sakai H, Nagao H, Sakurai M, Okumura T, Nagai Y, Shikuma J, Ito R, Imazu T, Miwa T, Odawara M. Correlation between Serum Levels of 3,3’,5’-Triiodothyronine and Thyroid Hormones Measured

by Liquid Chromatography-Tandem Mass Spectrometry and Immunoassay.

PLoS One. 2015 Oct 1;10(10):e0138864.

13. Miyagawa JI, Odawara M, Takamura T, et al.: Once weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomised phase 3 study. Diabetes Obes Metab. 2015 14. Rakugi H, Ogihara T, Saruta T, .., Odawara M, et al.: COLM Investigators. Preferable effects of olmesartan/calcium channel blocker to olmesartan/diuretic on blood pressure variability in very elderly hypertension: COLM study subanalysis. J Hypertens. 2015 15. Odawara M, Yoshiki M, Sano M, Hamada I, Lukashevich V, Kothny W. Efficacy and safety of a single-pill combination of vildagliptin and metformin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

Diabetes Ther. 2015 Mar;6(1):17-27.

16. Odawara M, Kadowaki T, Naito Y. Effectiveness and safety of basal supported oral therapy with insulin glargine, in Japanese insulinnaive, type 2 diabetes patients, with or without microvascular complications: subanalysis of the observational, non-interventional, 24-week follow-up Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA) study. J Diabetes Complications. 2015 17. Garg SK, Admane K, Freemantle N, Odawara M, et al.: Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational atlas study. Endocr Pract. 2015.

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Juliana Chan, MBChB, M.D., FHKAM, FRCP Professor Juliana Chan is Chair Professor of Medicine and Therapeutics and Director, Hong Kong Institute of Diabetes and Obesity and Director, Clinical Research Management Office, The Chinese University of Hong Kong, Prince of Wales Hospital. She graduated from the Liverpool University, UK and is a clinician scientist with accreditations in endocrinology and clinical pharmacology.

In 1995, she established the Hong Kong Diabetes Registry to characterize the clinical course and genetic associations of diabetes. In 2007, she established the Asia Diabetes Foundation and developed the web-based Joint Asia Diabetes Evaluation (JADE) Programme which demonstrated the benefits of using information technology and integrated care to improve clinical outcomes. The accompanying biobanks of these cohorts have also formed the basis of large scale projects to use multi-omic approaches to discover genetic causes of diabetes and its complications. She has trained more than 50 postgraduate students/fellows and co-authored 500 articles and 20 book chapters. She is a member of steering committees of international surveys and randomized outcome trials in diabetes and cardiovascular-renal disease. She is a recipient of the Peter Bennet Epidemiology Award and Asian Association for Study of Diabetes Epidemiology Award and is currently leading a Lancet Diabetes Commission to advocate the use of systems and policies to close the gaps in diabetes care, data and outcomes.

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Hnorary Guests

Solomon Tesfaye, MBChB, M.D., FRCP H-Index 50 on Google scholar Solomon Tesfaye is a Consultant Physician/Endocrinologist at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield. His research projects include the epidemiology, risk factors, pathogenesis, central nervous system involvement and treatment of diabetic neuropathy and neuropathic pain. He has published a book, over 180 original articles in diabetic neuropathy including a landmark study in the NEJM. Professor Tesfaye was awarded the Prestigious Camillo Golgi Prize of the EASD in 2014 for major scientific contributions in Diabetic Neuropathy. He also received the Arnold Bloom Award of Diabetes UK in 2017 for innovative and patient centered diabetes care. Prof Tesfaye served as Chair the International Expert Group on Diabetic Neuropathy 2010/11; and of NEURODIAB (2006-9) which is the largest diabetic neuropathy scientific group in the world. He is currently a member of the Diabetes Complications Clinical Studies Group of Diabetes UK, a member of the Advisory Council of the Neuropathy Trust and is Secretary of International Insulin Foundation. He is also the Associate Editor of Experimental Diabetes Research, Frontiers in Endocrinology, European Endocrinology and Diabetes Management and previously of Diabetologia. Professor Tesfaye also serves as grant review panel member for the JDRF and NIDDK; and has been a member of 3 NICE guideline committees on neuropathic pain management. Finally, he has received several research grants including: 5 project grants from Diabetes UK, JDRF, NIH, EFSD, NIHR and a recent £2.97m HTA award to investigate the most effective treatment pathway for painful diabetic neuropathy.

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Daisuke Koya, M.D., Ph.D. Education: 1984 1992

M.D. Ph.D.

Shiga University of Medical Science, Shiga, JAPAN Shiga University of Medical Science, Shiga, JAPAN

Hospital Appointment: 1984-1986 Intern and Resident in Internal Medicine, Shiga University of Medical Science,

Shiga, JAPAN 1986-1988 Associate Staff in Internal Medicine, Shinsenri Hospital, Osaka, JAPAN 1988-1992 Associate Staff in Internal Medicine, Shiga University of Medical Science, Shiga,

JAPAN 1992-1994 Assistant Professor in Internal Medicine, Shiga University of Medical Science,

Shiga, JAPAN 1997- Assistant Professor in Internal Medicine, Shiga University of Medical Science,

Shiga, JAPAN 2004- Associate Professor in Internal Medicine, Shiga University of Medical Science,

Shiga, JAPAN 2005- Professor, Division of Diabetology & Endocrinology, Kanazawa Medical University Postdoctoral Training: 1985-1992 Fellowships in Internal Medicine, Shiga University of Medical Science, Shiga,

JAPAN 1992-1994 Research Instructor in Internal Medicine, Shiga University of Medical Science,

Shiga, JAPAN 1994-1997 Postdoctoral Fellowships in Section on Vascular Cell Biology, Joslin Diabetes

Center, Boston, MA, USA Licensure and Certification: 1984 Medical License, JAPAN 1988 Internal Medicine-Certification for Specialty Board 1999 Japan Diabetes Society-Certification for Specialty Board

Japanese Society of Nephrology-Certification for Specialty Board

Japanese Society of Dialysis Therapy-Certification for Specialty Board 2007 Japanese Society of Metabolism and Clinical Nutrition-Certification for Specialty Board Awards and Honors: 2000 Young Investigator Award from Japan Society of Diabetic Complications 2003 Grant-in-Aid of The Japan Medical Association 2014 Grant-in Aid of Genpaku Sugita Editorial Board 2009 World Journal of Diabetes 2010 Journal of Diabetes Research 2014 Clinical Science 26

Hnorary Guests Association core member 2000 Japan Diabetes Association 2000 Japan Nephrology Society 2005 Japan Nutrition Society 2010 Japan-anti aging society Grant funding 2016-2018 Challenging Exploratory Research, Grants-in-Aid for Scientific Research from

Japan Society for the Promotion of Science 2013-2015 Scientific Research (B), Grants-in-Aid for Scientific Research from Japan Society

for the Promotion of Science 2013-2015 Challenging Exploratory Research, Grants-in-Aid for Scientific Research from

Japan Society for the Promotion of Science 2010-2012 Scientific Research (C), Grants-in-Aid for Scientific Research from Japan Society

for the Promotion of Science 2005-2007 Scientific Research (C), Grants-in-Aid for Scientific Research from Japan Society

for the Promotion of Science 2003-2005 Scientific Research (C), Grants-in-Aid for Scientific Research from Japan Society

for the Promotion of Science 2000-2002 Scientific Research (C), Grants-in-Aid for Scientific Research from Japan Society

for the Promotion of Science 1998-2000 Scientific Research (C), Grants-in-Aid for Scientific Research from Japan Society

for the Promotion of Science 1993-1994 Grant-in-Aid for Young Scientists(B), Grants-in-Aid for Scientific Research from

Japan Society for the Promotion of Science Research Interest Diabetes and its complications, Aging、Endocrinology Publications (latest sequence) 1. Ipragliflozin improves mitochondrial abnormalities in renal tubules induced by a high-fat diet.

Takagi S, Li J, Takagaki Y, Kitada M, Nitta K, Takasu T, Kanasaki K, Koya D. J Diabetes Investig.

2018 Jan 20. doi: 10.1111/jdi.12802.

2. FGFR1 is essential for N-acetyl-seryl-aspartyl-lysyl-proline regulation of mitochondrial dynamics by upregulating microRNA let-7b-5p. Hu Q, Li J, Nitta K, Kitada M, Nagai T, Kanasaki K, Koya D. Biochem Biophys Res Commun. 2018 Jan 15;495(3):2214-2220.

3. The Effect of Piceatannol from Passion Fruit (Passiflora edulis) Seeds on Metabolic Health in Humans. Kitada M, Ogura Y, Maruki-Uchida H, Sai M, Suzuki T, Kanasaki K, Hara Y, Seto H, Kuroshima Y, Monno I, Koya D. Nutrients. 2017 Oct 18;9(10). pii: E1142. doi: 10.3390/nu9101142 4. Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS. Shimizu M, Furuichi K, Toyama T, Funamoto T, Kitajima S, Hara A, Ogawa D, Koya D, Ikeda K, Koshino Y, Kurokawa Y, Abe H, Mori K, Nakayama M, Konishi Y, Samejima KI, Matsui M, Yamauchi H, Gohda T, Fukami K, Nagata D, Yamazaki H, Yuzawa Y, Suzuki Y, Fujimoto S, Maruyama S, Kato S, Naito T, Yoshimura K, Yokoyama H, Wada T; Research Group of Diabetic Nephropathy, the Ministry of Health, Labour, and Welfare of Japan and Japan Agency for Medical Research and Development.

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Clin Exp Nephrol. 2017 Sep 9. doi: 10.1007/s10157-017-1467-9.

5. Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance. Wada T, Ishikawa A, Watanabe E, Nakamura Y, Aruga Y, Hasegawa H, Onogi Y, Honda H, Nagai Y, Takatsu K, Ishii Y, Sasahara M, Koya D, Tsuneki H, Sasaoka T. J Endocrinol. 2017 Aug 30. pii: JOE-170351. doi: 10.1530/JOE-17-0351.

6. A cyclic and intermittent very low-protein diet can have beneficial effects against advanced diabetic nephropathy in Wistar fatty (fa/fa) rats, an animal model of type 2 diabetes and obesity. Kitada M, Ogura Y, Suzuki T, Monnno I, Kanasaki K, Watanabe A,Koya D. Nephrology (Carlton). 2017 Aug 12. doi: 10.1111/nep.13152.

7. Deficiency in catechol-o-methyltransferase is linked to a disruption of glucose homeostasis in mice.

Kanasaki M, Srivastava SP, Yang F, Xu L, Kudoh S, Kitada M, Ueki N, Kim H, Li J, Takeda S, Kanasaki K, Koya D. Sci Rep. 2017 Aug 11;7(1):7927.

8. FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N-acetyl-seryl-aspartyllysyl-proline via induction of the MAP4K4 pathway. Li J, Shi S, Srivastava SP, Kitada M, Nagai T, Nitta K, Kohno M, Kanasaki K, Koya D. Cell Death Dis. 2017 Aug 3;8(8):e2965.

9. Catechol-O-Methyltransferase Deficiency Leads to Hypersensitivity of the Pressor Response Against Angiotensin II. Ueki N, Kanasaki K, Kanasaki M, Takeda S, Koya D. Hypertension. 2017 Jun;69(6):1156-1164.

10. Regulating Autophagy as a Therapeutic Target for Diabetic Nephropathy. Kitada M, Ogura Y, Monno I, Koya D. Curr Diab Rep. 2017 Jul;17(7):53.

11. Anagliptin ameliorates albuminuria and urinary liver-type fatty acid-binding protein excretion in patients with type 2 diabetes with nephropathy in a glucose-lowering-independent manner. Kitada M, Tsuda SI, Konishi K, Takeda-Watanabe A, Fujii M, Kanasaki K, Nishizawa M, Nakagawa A, Koya D. BMJ Open Diabetes Res Care. 2017 Jul 7;5(1):e000391.

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Ying-Wei Wang, M.D., Ph.D. Personal Information Nationality: Taiwan Position: Director-General Organization: Health Promotion Administration: Ministry of Health & Welfare: Taiwan: R. O. C. Email: ywwang@hpa.gov.tw Educational background & professional experience (in sequence of the latest year) Year Department/Organization 2011/09-2016/06 Department of Medicine, Tzu Chi University.

2011/09-2016/06 Department of Medical Humanities, Director

School of Medicine, Tzu Chi University.

2011/10-2016/06 Taiwan Society of Health Promotion Hospitals.

1989/05-2016/06 Department of Family Medicine,

Buddhist Tzu Chi General Hospital.

2005/09- 2010/06 Center for Faculty Development and Instructional

Resources, Tzu Chi University.

2003/11-2005/08 Bureau of Health Promotion, Department of Health,

Taiwan.

1989/05-2016/06 Department of Family Medicine, Buddhist Tzu Chi

General Hospital.

1985/07-1989/04 Department of Geriatrics, Taipei Hospital.

1982/07-1985/06 Department of Family Medicine, National Taiwan

University Hospital.

1993-1999 School of Public Health & Tropical Medicine,

Tulane University, U.S.A. 1992-1993 School of Public Health & Tropical Medicine,

Tulane University, U.S.A. 1975-1982 School of Medicine, National Taiwan University,

Taiwan

Position Deputy Director Secretary-general Director Director Deputy Director General Attending Physician Attending Physician Resident Dr.P.H. M.P.H. M.D.

Research Interests (Major) 1. Family Medicine 2. palliative care 3. Community Health 4. health promotion 5. medical education

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Publications (5 important publications – latest sequence) 1. Mi-Hsiu Wei1, Ying-Wei Wang, Mei-Chuan Chang, Jyh-Gang Hsieh. Development of Mandarin Multidimensional Health Literacy Questionnaire (MMHLQ) Taiwan J Public Health 2017;36(6):556570 2. Jyh-Gang Hsieh, Ying-Wei Wang. An anthropological approach to teach and evaluate cultural competence in medical students the application of mini-ethnography in medical history taking. : Med Educ Online 2016, 21: 3256 3. Lee CB, ChenMS, Wang YW. Barriers to and facilitators of the implementation of health promoting hospitals in Taiwan: a top-down movement in need of ground support Int J Health Plann Mgmt 2012;29(2):197-213 4. Wang WL., Wang YW. The Application of Microteaching to Improve Teaching Skill in Medical School J Med Education 2012; 16: 159∼166 5. Jyh-Gang Hsieh, Ying-Wei Wang. Application of signs of dying identified in traditional Chinese, Tibetan, and modern Western medicine in terminal care. Tzu Chi Medical Journal, 2012; 24(1), 1215.

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Hnorary Guests

Po-Chang Lee, M.D. Personal Information Title: 1. D irector General, National Health Insurance

Administration,Ministry of Health and Welfare 2. Chairperson of the Board, Taiwan Organ Registry and Sharing Center 3. Professor of Surgery, Medical College, National Cheng Kung University Degree: 1. Taipei Medical College, Taiwan 2. Master of Law. National Cheng Kung University, Taiwan Nationality: TAIWAN Position: Director General Organization: National Health Insurance Administration,Ministry of Health and Welfare Email: hhtai@nhi.gov.tw Educational background & professional experience (in sequence of the latest year) Year Department/Organization Position 2011~ Taiwan Organ Registry and Sharing Center Chairperson of the Board 2001~ Medical College, National Cheng Kung University Professor of Surgery 2012-2016/05 Tainan Hospital, Ministry of Health and Welfare Superintendent 2008~2011 The Transplantation Society of Taiwan President 2004-2007 Department of Surgery, National Cheng Kung Chairman

University Hospital 2005-2008 National Cheng Kung University, Taiwan Master of Law 1994-1995 University of California, Los Angeles, USA Postdoctoral Scholar 1993-1994 Kyoto Prefectural University of Medicine, Japan Visiting Scientist 1971-1979 Taipei Medical College, Taiwan M.D. Research Interests (Major) 1. 1995/06Visiting Scholar, University of Minnesota, USA 2. 1995/05Visiting Scholar, Johns Hopkins University, USA 3. 1993/03Visiting Scholar, National Cancer Center, Japan

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社團法人中華民國內分泌暨糖尿病學會 第 13 屆第 3 次會員大會暨學術研討會 日期：民國 107 年 3 月 10-11 日／地點：台大醫院國際會議中心

March 10, 2018

PL1: Plenary Lecture 1

【101 Room】 Time 13:20-13:30 PL-1 13:30-14:15

Topic OPENING

Time

Topic

32

Moderator

Yutaka Seino

許惠恒

PL3: Plenary Lecture 3

Time

曾芬郁

許惠恒

PROMOTING DIABETES RESEARCH FOR BETTER DIABETES CARE IN ASIA: FOCUS ON INSULIN SECRETION AND INCRETINS

【101 Room】

PL-3 09:50-10:30

Speaker

OPENING

March 11, 2018

09:45-09:50

Rossella Elisei

PL2:Plenary Lecture 2

【101 Room】

PL-2 14:20-15:00

Moderator 曾芬郁

TARGET THERAPIES IN ADVANCED THYROID CANCER

March 10,2018

14:15-14:20

Speaker

Topic

Speaker

OPENING THYROID CANCER-FROM BEDSIDE TO BENCH

Moderator 林宏達

林仁德

林宏達

Agenda

March 11,2018

PL4: Plenary Lecture 4

【101 Room】 Time

Topic

13:30-13:35 PL-4 13:35-14:15

Speaker

OPENING

Moderator 莊立民

GENETIC MANIPULATION TOWARDS IMMUNE TOLERANCE: APPROACHES

BY TRANSGENIC AND KNOCKOUT/ KNOCKDOWN MOUSE MODELS

司徒惠康

莊立民

DAROC-TADE Joint Symposium

March 10 , 2018 【101 Room】

2018 台灣糖尿病高血脂醫療合併照護及政策 Time

Topic

08:00~08:20

報到

08:20~08:30

OPENING

Speaker Moderator

杜思德

DAROC-TADE1 08:30~09:10

台灣糖尿病高血脂指引之說明

洪晧彰

杜思德

DAROC-TADE2 09:10~09:50

血脂治療新選擇 PCSK9 抑制劑

吳卓鍇

陳榮福

從糖尿病防治暨其合併症談臺灣醫 療整合照護展望

王英偉

蔡世澤

醫學中心到基層醫療健保： 糖尿病疾病照護的未來

李伯璋

李洮俊

09:50~10:00 DAROC-TADE3

0:00~10:50

DAROC-TADE4 10:50~11:40

COFFEE BREAK

11:40~11:50

PANEL DISCUSSION

許惠恒 杜思德

11:50-12:00

CLOSING

許惠恒

33

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 10, 2018 【301 Room】

MTP-1: Meet the Professor-1

Time MTP-1 12:00-13:00

March 10, 2018 【402AB Room】

Topic AUTOIMMUNITY AND THYROID CARCINOMA

March 10, 2018 【301 Room】

Topic CLINICAL MANAGEMENT OF TYPE 2 DIABETES WITH CHRONIC KIDNEY DISEASE IN JAPAN: CURRENT SITUATION AND STRATEGY

Speaker Moderator Abe Masanori

Topic

Speaker Moderator

OPENING GRAVES’ OPHTHALMOPATHY -CLINICAL EXPERIENCES IN KOREA

Jeehee Yoon

SE1-2 15:50-16:10

MEDICAL TREATMENT OF GRAVES’ ORBITOPATHY

施翔蓉

SE1-3 16:10-16:30

THE STRATEGY FOR THE MANAGEMENT OF GRAVES’ OPHTHALMOPATHY

魏以宣

34

莊立民

ESROC and KES Joint Symposium

SE1-1 15:30-15:50

16:30-16:40

張天鈞

SE1: Endocrine Symposium 1

Time 15:20-15:30

Rosella Elisei

MTP-1: Meet the Professor-2

Time MTP-2 17:00-18:00

Speaker Moderator

CLOSING

曾芬郁 Dongsun Kim

Agenda

March 10, 2018 【402CD Room】

SE2: Endocrine Symposium 2

New progress in treatment and diagnosis of thyroid diseases

Time

Topic

Speaker

SE2-1 15:25-15:45

CONTRAST-ENHANCED ULTRASOUND (CEUS) OF THE THYROID GLAND

周宜宏

SE2-2 15:45-16:05

MOLECULAR TESTING IN CYTOLOGICAL INDETERMINATE THYROID NODULES

劉瑞川

SE2-3 16:05-16:25

CURRENT CONCEPT FOR THYROID RADIOFREQUENCY ABLATION

林偉哲

SE2-4 16:25-16:45

NEW APPLICATION OF GENETIC TESTING IN CLINICAL DIAGNOSIS

蘇怡寧

15:20-15:25

16:45-16:50

March 11, 2018 【401 Room】

OPENING

王佩文 陳涵栩

CLOSING

SE3: Endocrine Symposium 3

Taiwan Society of Aldosteronism Joint Symposium

Time

SE3-1

Moderator

Topic

8:00-8:05

OPENING

8:05-8:35

NATIONAL PA REGISTRY-BASED EVIDENCE FOR CLINICAL PRACTICE OF PRIMARY ALDOSTERONISM IN JAPAN

Speaker Moderator

Mitsuhide Naruse 曾芬郁 吳寬墩

SE3-2

8:35-9:05

ADRENAL VENOUS SAMPLING IN NTUH

張晉誠

SE3-3

9:05-9:35

CASE DETECTION AND DIAGNOSIS OF PRIMARY ALDOSTERONISM -THE CONSENSUS OF TAIWAN SOCIETY OF ALDOSTERONISM

胡雅惠

9:35-9:40

PANEL DISCUSSION

吳允升 35

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 11 , 2018 【402 AB Room】

SE4: Endocrine Symposium 4

Thyroid nodules and differentiated carcinoma clinical manual

Time

Topic

Speaker Moderator

8:00-8:05

OPENING

SE4-1

8:05-8:20

從偶發性的甲狀腺結節談起

陳涵栩

SE4-2

8:20-8:35

甲狀腺細針穿刺細胞學檢查

林樹福

SE4-3

8:35-8:50

細胞學檢查後的部份對策

施翔蓉

SE4-4

8:50-9:05

懷孕期間發現的結節處置

蘇登煌

SE4-5

9:05-9:20

分化型甲狀腺癌的術後風險分期與放射性 碘治療

張雁翔

9:20-9:25

CLOSING

March 11 , 2018 【401 Room】

SE5: Endocrine Symposium 5 Pheochromocytoma

Time 14:45-14:50

Topic

Speaker Moderator

OPENING

SE5-1 14:50-15:30

UP-TO-DATE OF CLINICAL PRACTICE OF PHEOCHROMOCYTOMA/ PARAGANGLIOMA

SE5-2 15:30-15:55

GENETICS AND DIAGNOSIS OF PHEOCHROMOCYTOMA/ PARAGANGLIOMA

陳沛隆

SE5-3 15:55-16:20

SURGICAL TREATMENT OF PHEOCHROMOCYTOMA

黃國皓

16:20-16:35 36

陳思達 劉鳳炫

PANEL DISCUSSION

Mitsuhide Naruse

張慶忠

Agenda

March 11 , 2018 【402AB Room】

SE6: Endocrine Symposium 6 Lipid forum

Time 14:45-14:50

Topic

Speaker Moderator

OPENING

SE6-1 14:50-15:15

CURRENT CHALLENGES IN THE TREATMENT OF PATIENTS WITH HYPERLIPIDEMIA

SE6-2 15:15-15:40

PCSK9 INHIBITORS, A NEW THERAPEUTIC REGIMEN FOR PATIENTS WITH DYSLIPIDEMIA- FROM JAPAN’S PERSPECTIVE.

楊偉勛

Masato Odawara 黃天祥 蔡克嵩

SE6-3 15:40-16:05

THE ROLE OF PCSK9 INHIBITORS FOR LDL-C REDUCTION IN DIABETIC PATIENT WITH ASCVD- FROM ENDOCRINOLOGIST POINT OF VIEW

歐弘毅

SE6-4 16:05-16:30

EVIDENCE-BASED PCSK9 INHIBITORS: FROM BENCH TO CLINIC AND ITS PROSPECT

林維文

16:30-16:35

March 10 ,2018 【401Room】

CLOSING

SD1: Diabetes Symposium 1

DM and Geriatric syndrome: Muscle and Brain

Time 15:20-15:25

Topic

Speaker Moderator

OPENING

SD1-1 15:25-16:10

FRAILTY AND SARCOPENIA IN OLDER ADULTS WITH DIABETES MELLITUS

陳亮恭

陳榮福

SD1-2 16:10-16:55

COGNITIVE IMPAIRMENT AND DIABETES: RECIPROCAL RELATIONS AND CLINICAL IMPLICATIONS

王培寧

何橈通

16:55-17:00

CLOSING 37

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 11,2018 【101Room】

SD2: Diabetes Symposium 2

2018 DAROC clinical practice guidelines for diabetes care

Time 08:00-08:05

Topic

Speaker Moderator

OPENING

SD2-1 08:05-08:30

糖尿病照護指引摘要

李弘元

洪乙仁

SD2-2 08:30-08:55

妊娠糖尿病的診斷與治療

郭俊亨

陳清助

SD2-3 08:55-09:20

糖尿病治療的新進展

朱志勳

謝明家

09:20-09:30

March 11,2018 【301 Room】

CLOSING

SD3: Diabetes Symposium 3 Clinical management in diabetes

Time 08:00-08:05

Topic

Speaker Moderator

OPENING

SD3-1 08:05-08:45

ORAL ANTIHYPERGLYCEMIC THERAPY IN T2DM PATIENTS WITH ASCVD – EVIDENCE AND CLINICAL PRACTICE RECOMMENDATIONS

Juliana Chan

杜思德

SD3-2 08:45-09:25

THERAPEUTIC ADVANCES WITH NEW INSULIN ANALOGUE AND GLP-1RA BASED ON RECENT CVOT RESULTS

Masato Odawara

蔡世澤

09:25-09:30

38

CLOSING

Agenda

March 11,2018 【402CD Room】

SD4: Diabetes Symposium 4

Basic research in diabetes and endocrinology

Time 08:00-08:05

Topic

Speaker

Moderator

OPENING

SD4-1 08:05-08:45

PROTECTIVE ROLE OF THYROID HORMONE IN LIVER CARCINOGENESIS

林光輝

莊峻鍠

SD4-2 08:45-09:25

ROLE OF ADIPOCYTE HYPERTROPHY AND HYPOXIA IN THE DEVELOPMENT OF OBESITY-ASSOCIATED ADIPOSE TISSUE INFLAMMATION AND INSULIN RESISTANCE – THE INVOLVEMENT OF COX-2 ACTIVATION

謝博軒

楊偉勛

09:25-09:30

March 11,2018 【101 Room】

CLOSING

SD5: Diabetes Symposium 5

Diabetes and Nervous System: Brain and Peripheral Nerves

Time 14:45-14:50

Topic

Speaker

Moderator

OPENING

SD5-1 14:50:15:35

DIABETIC NEUROPATHY: PERCEPTION Solomon BEYOND THE SEAM OF THE Tesfaye PERIPHERY

黃禹堯

SD5-2 15:35-16:20

GLYCEMIC CONTROL FOR PATIENTS WITH CEREBROVASCULAR DISEASE

戴東原

16:20-16:25

鄭建興

CLOSING

39

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 11,2018 【301 Room】

SD6: Diabetes Symposium 6

Diabetes and Kidney: From Diabetologist’s and Nephrologist’s View

Time

Topic

Speaker

Moderator

SD6-1 14:50:15:35

GROWING CHALLENGE OF DIABETIC NEPHROPATHY

Daisuke Koya

辛錫璋

SD6-2 15:35-16:20

GLUCOSE CONTROL IN DIABETIC PATIENTS WITH MODERATE AND ADVANCED KIDNEY DISEASE

林俊良

許惠恒

14:45-14:50

16:20-16:25

March 10 ,2018 【402AB Room】

OPENING

CLOSING

YL: Young Investigator Research Lecture

Time

YL-1

Topic

Speaker

15:20-15:30

OPENING

15:30-15:50

第 2 型糖尿病小鼠模式腎臟中之前列腺素 E2 代謝產物表現的研究

林志弘 辛錫璋

YL-2

15:50-16:10

母系遺傳粒線體缺損造成胰島素阻抗性之 機轉

張以承

YL-3

16:10-16:30

胰淀素 (AMYLIN) 與新生糖尿病及肥胖的 關係

范綱志

YL-4

40

16:30-16:50

探討 FNDC5/irisin 於高血糖和肥胖之胰臟 內和胰島素分泌與胰島細胞增生之關聯

16:50-17:00

CLOSING

Moderator

黃建寧 吳忠擇

Agenda

AP: 2018 Award

March 11 , 2018

Grant Award Lectures

【402CD Room】 Time 14:45-14:50

Topic

Speaker

Moderator

OPENING 諾華優秀論文獎

AP-1

14:50-15:10

THE HEPATIC PROTECTION EFFECTS OF HEPASSOCIN IN HYPERGLYCEMIC CRISIS

歐弘毅

AP-2

15:10-15:30

EFFICACY OF A HSP90 INHIBITOR, GANETESPIB, IN PRECLINICAL THYROID CANCER MODELS

林樹福

諾和諾德優秀論文獎 AP-3

15:30-15:50

LOWER RISK OF DEMENTIA WITH PIOGLITAZONE, COMPARED WITH OTHER SECOND-LINE TREATMENTS, IN METFORMIN-BASED DUAL THERAPY: A POPULATION-BASED LONGITUDINAL STUDY

盧介祥

AP-4

15:50-16:10

USEFULNESS OF THE PLASMA GLUCOSE CONCENTRATION-TOHBA1C RATIO IN PREDICTING CLINICAL OUTCOMES DURING ACUTE ILLNESS WITH EXTREME HYPERGLYCEMIA.

蘇郁文

16:10-16:20

CLOSING

葉振聲 王治元

41

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS: Lunch Symposium Room 101

Room 301

Room 401

Room 402AB

Room 402CD

Room 202

Room 203

March 10 12:00-13:00

LS1

LS2

LS3

LS4

LS5

LS6

台灣諾華

台灣禮來

台灣諾華

阿斯特捷利康

諾和諾德

輝瑞

April 9 12:10-13:20

LS7

LS8

LS9

LS10

LS11

LS12

LS13

美敦力

台灣禮來

賽諾菲

默沙東

安斯泰來

亞培

友華

March 10, 2018

Topic

Speaker

Moderator

LS-1

台灣 諾華

JAPAN EXPERIENCE IN MANAGING OLDER T2DM: ROLE OF DPP4I AS THE FIRST LINE THERAPY

Daisuke Koya

胡啟民

LS-2

台灣 禮來

UTILIZING TRULICITY WITH INSULIN: WHAT ARE THE CLINICAL IMPLICATIONS AND HOW DOES THIS HELP OUR PATIENTS

Iain Cranston

許惠恒

LS-3

台灣 諾華

OPTIMIZING THE TREATMENT OF ACROMEGALY PATIENTS WITH 1ST GENERATION SSA AND 2ND GENERATION SSA

張宏猷

陳榮福

LS-4

阿斯特 捷利康

LS-5

LS-6

REDUCING THE BURDEN OF T2DM: Alexander NOVEL MEDICATION BY COMBINATION Tan OF METFORMIN AND SGLT2 INHIBITORS

黃禹堯

諾和 諾德

A PRACTICAL APPROACH FOR BASAL INSULIN TREATMENT WITH CONFIDENCE

楊宜瑱

黃建寧

輝瑞

HIDDEN FACE OF DIABETES: DIABETIC DYSLIPIDEMIA MANAGEMENT AND EVIDENCES OF STATIN IN ASIAN

Juliana Chan

HIDDEN FACE OF DIABETES: WHY SHOULD WE CARE DIABETIC NEUROPATHY AND HOW TO MANAGEMENT 42

Solomon Tesfaye

莊立民

Agenda

March 11, 2018 LS-7

美敦力

TOPIC

Speaker

Moderator

THE BENEFIT OFSMART GUARD INSULIN PUMP FROM CLINICAL PROSPECTIVE

林嘉鴻

羅福松

王治元

蔡世澤

Masato Odawara

曾芬郁

LS-8 台灣禮來 THE HEART OF DIABETES: 百靈佳殷 BASE ON CURRENT T2D TREATMENT 格翰 STRATEGIES AND GUIDELINES LS-9

賽諾菲

ROLE OF NEW BASAL INSULIN ANALOGUE TOUJEO BASED ON CLINICAL STUDY RESULTS AND REAL WORLD EVIDENCE INCLUDING EXPERIENCES IN JAPAN

LS-10

默沙東

BEYOND THE 10 YEARS : WHERE DO DPP-4 INHIBITORS FIT WITHIN TODAY´S TREATMENT PARADIGM FOR PATIENTS WITH TYPE 2 DIABETES

朱志勳

洪乙仁

LS-11

安斯 泰來

IMPROVING CARDIOVASCULAR AND RENAL OUTCOMES IN GOUTHYPERURICEMIA: WHAT SHOULD WE TARGET?

Austin Stack

許惠恒

LS-12

亞培

POTENTIAL ROLE OF POC A1C TESTING IN PRACTICE

朱芳業

羅世慧

謝明家

陳榮福

LS-13

友華

THE BENEFITS OF HIGH INTENSITY STATIN TREATMENT - FROM REAL-CAD STUDY

43

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 10, 2018 【401 Room】 Time

OE: Oral Presentation-Endocrine Topic

Speaker Moderator

OE-1

17:00-17:10

THE SYNERGISTIC EFFECT OF RENALASE AND CHRONIC KIDNEY DISEASE ON ENDOTHELIN-1 IN SUBJECTS WITH ESTABLISHED CORONARY ARTERY DISEASE A CROSS-SECTIONAL STUDY

李宇璇

OE-2

17:10-17:20

TREATMENT EFFICACY AND SAFETY OF ULTRASOUND-GUIDED PERCUTANEOUS RADIOFREQUENCY ABLATION FOR BENIGN THYROID NODULES: KCGMH EXPERIENCE

林偉哲

OE-3

17:20-17:30

LOW-DOSE ADEFOVIR THERAPY RELATED OSTEOMALACIA MIMICKING MULTIPLE BONE METASTASIS - A CASE SERIES STUDY

劉仕朋 簡銘男 李亭儀

OE-4

17:30-17:40

A NOVEL MISSENSE MUTATION OF THE MEN1 GENE IN CHINESE FAMILY WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 1

梁博智

OE-5

17:40-17:50

EXPERIENCE OF IODINE-131 METAIODOBENZYLGUANIDINE THERAPY OF MALIGNANT PHEOCHROMOCYTOMA IN CCH

林思涵

OE-6

17:50-18:00

GENETIC STUDY FOR COMBINED PITUITARY HORMONE DEFICIENCY IN TWO SIBLINGS

溫緯倫

44

Agenda

March 10, 2018 【301 Room】 Time

OD: Oral Presentation-Diabetes Topic

Speaker Moderator

OD-1

17:00-17:10

ADAM10 MODULATES CALCITRIOLREGULATED RAGE IN CARDIOMYOCYTES

李亭衛

OD-2

17:10-17:20

THE CHANGE OF THE BONE STRUCTURE AND MICROARCHITECTURE AFTER ORAL ANTIDIABETIC DRUG TREATMENT IN DIET-INDUCED OBESITY MICE

曹政峰

OD-3

17:20-17:30

CHANGES OF GUT MICROBIOTA IN NEWLY-DIAGNOSED TYPE 2 DIABETES TREATED WITH METFORMIN MONOTHERAPY

洪薇雯

OD-4

17:30-17:40

LEVELS OF SERUM HIGH MOBILITY GROUP BOX 1 WERE INDEPENDENTLY ASSOCIATED WITH CARDIOVASCULAR RISK IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY

王俊興 李建興 林昆德

OD-5

17:40-17:50

EVALUATION OF GLYCEMIC CONTROL AND SELF-EFFICACY AMONG PATIENTS RECEIVING CONTINUOUS GLUCOSE MONITORING WITH IMMEDIATE COUNSELING FEEDBACK COMPARED WITH DELAYED COUNSELING FEEDBACK

杜業豐

OD-6

17:50-18:00

PREVALENCE, INCIDENCE, AND RISK FACTORS OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES - AN 8-YEAR PROSPECTIVE COHORT STUDY IN A COMMUNITY HOSPITAL

許志成

45

39

The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 10-11,2018

PE: Poster Presentation-Endocrine 主持人： 吳婉禎、蘇登煌、邱偉益 題 目

第一作者

PE-1

REPETITIVE SEIZURE AS THE INITIAL PRESENTATION IN A PATIENT WITH PSEUDOHYPOPARATHYROIDISM: A CASE REPORT

于念主

PE-2

CATECHOLAMINE - INDUCED CARDIOMYOPATHY IN A 37 YEAR-OLD WOMAN WITH INITIAL PRESENTATION AS CARDIOGENIC SHOCK

林榆培

PE-3

HYPOTHYROIDISM WITH HIGH LEVEL OF FT4

韋佳齡

PE-4

UNDERWEIGHT INCREASES THE RISK OF EARLY DEATH IN TUBERCULOSIS PATIENTS: A POPULATION-BASED STUDY

顏永豐

PE-5

A VERY RARE CASE OF PULMONARY LYMPHANGITIC CARCINOMATOSIS IN PATIENT WITH RECURRENT PAPILLARY THYROID CARCINOMA

黃則穎

PE-6

PITUITARY PLURIHORMONAL ADENOMA SECRETING TSH AND ALH –A CASE REPORT

林玉怡

PE-7

PARATHYROID ADENOMA PRESENTED WITH HYPOCALCEMIA IN A PATIENT WITHOUT CHRONIC RENAL INSUFFICIENCY

林軒維

PE-8

THYROID MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA IN A 63-YEAR-OLD WOMAN : A CASE REPORT

王新瑋

PE-9

131I ABLATION THERAPY IN PATIENT WITH THYROID CANCER AND ESRD ON HEMODIALYSIS: CASE REPORT

王志仁

PE-10

BILATERAL ADRENAL GLAND HEMORRHAGE: A CASE REPORT AND REVIEW OF THE LITERATURE

陳永年

PE-11

DECIPHERING THE REGULATORY CODE OF THE RELATIONSHIP BETWEEN THE CHOLINE TRIMETHYLAMINE LYASE (CUTC) AND CARDIOVASCULAR DISEASES

李明彰

46

Agenda

題 目

第一作者

PE-12

LONG-TERM THERAPEUTIC OUTCOME OF PAPILLARY THYROID CARCINOMA WITH HYPERPARATHYROIDISM: A CASE-CONTROL STUDY

蔡之祐

PE-13

CASE REPORT: HYPERTROPHIC OSTEOARTHROPATHY IN 21 YEARS OLD YOUNG MAN

陳威麟

PE-14

ACROMESOMELIC DYSPLASIA MAROTEAUX TYPE WITH VITAMIN D DEFICIENCY -A CASE REPORT

林玉怡

PE-15

HUGE PARATHYROID MASS WITH HYPERCALCEMIC CRISIS: A CASE REPORT

謝寶龍

PE-16

LITHIUM-INDUCED HYPOTHYROIDISM: A CASE REPORT

楊晉州

PE-17

COMPUTER-AIDED DIAGNOSTIC TECHNIQUE IN FDG POSITIVE THYROID NODULE– A CLINICAL EXPERIENCE OF 73 NON-THYROID CANCER PATIENTS

林怡瑄

PE-18

PARAGANGLIOMA AT CAROTID BIFURCATION PRESENTING AS CAROTID BODY TUMOR, COEXISTENCE WITH PAPILLARY THYROID CARCINOMA: A DIAGNOSIS DILEMMA

PE-19

GRAVES’ DISEASE COMPLICATED WITH HASHIMOTO ENCEPHALOPATHY: A CASE REPORT AND REVIEW OF LITERATURE

花士哲

PE-20

THYROID CANCER PRESENTED WITH AN INTERRUPTED PERIPHERAL CALCIFICATION IN SONOGRAPHY —A CASE REPORT

徐維信

PE-21

A CASE REPORT OF CUSHING DISEASE RELATED MULTISYSTEM FAILURE.

潘筱芳

PE-22

THE EFFECT OF THYROXINE SUPPRESSION THERAPY ON GOITER SIZE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN

陳瓊雅

PE-23

STEMNESS ACTIVATION IN ADRENAL CORTICOMEDULLARY MIXED TUMOR STUDIED BY WHOLE EXOME SEQUENCING

邱馨瑩

PE-24

CLINICAL SIGNIFICANCE OF HEPATIC I-131 UPTAKE IN THYROID CANCER

李宜螢

周璠

47

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

題 目

第一作者

PE-25

FALSELY HIGH RESULTS IN MULTIPLE HORMONE IMMUNOASSAYS – A CASE REPORT

徐惠娟

PE-26

CLINICOPATHOLOGICAL FEATURES OF PAPILLARY THYROID CARCINOMA PATIENTS WITH POSITIVE BRAF V600E MUTATION: SINGLE CENTER EXPERIENCE IN TAIWAN

姜和均

PE-27

METASTATIC POORLY DIFFERENTIATED THYROID CARCINOMA ARISING IN STRUMA OVARII WITH COEXISTENCE OF GRAVES` DISEASE AND MICROPAPILLARY THYROID CARCINOMA

謝雅湄

PE-28

SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR PREDICTING REDUCTION IN PULSE PRESSURE AFTER A ONEHOUR REST IN NURSES WORKING NIGHT SHIFTS

李奕德

PE-29

HEPATOTOXICITY OF PROPYLTHIOURACIL (PTU) IN A BOY WITH GRAVES DISEASE

李燕晉

March 10-11,2018

PD: Poster Presentation-Diabetes 主持人：李奕德、朱志勳、王俊興、李弘元 題 目

第一作者

PD-1

MATERNAL AND FETAL OUTCOMES OF PREGNANT WOMEN WITH TYPE 1 DIABETES, A NATIONAL POPULATION STUDY

林樹福

PD-2

TPL2 (THERAPEUTIC TARGETING TUMOR PROGRESSION LOCUS-2)/ATF4 (ACTIVATING TRANSCRIPTION FACTOR-4)/ SDF1Α (CHEMOKINE STROMAL CELL-DERIVED FACTOR-Α) AXIS SUPPRESSES DIABETIC RETINOPATHY

賴德偉

PD-3

HIGH GLUCOSE VARIABILITY INCREASES RE-ADMISSION RATES WITHIN 30 DAYS OF DISCHARGE IN DEPARTMENT OF SURGERY

謝靜蓉

PD-4

EFFECT OF GLP-1 RECEPTOR AGONIST ON PATIENTS WITH TYPE 2 DIABETES IN REAL PRACTICE: EXPERIENCE FROM A REGIONAL HOSPITAL

汪偉建

48

Agenda

題 目

第一作者

PD-5

EMPAGLIFLOZIN REPLACEMENT FOR DIPEPTIDYL PEPTIDASE-4 INHIBITORS IMPROVES GLYCATED HEMOGLOBIN IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES

黃瓊慧

PD-6

ASSOCIATION BETWEEN SERUM BILIRUBIN LEVELS AND PROGRESSION OF ALBUMINURIA IN TAIWANESE WITH TYPE 2 DIABETES MELLITUS

陳維健

PD-7

A CASE REPORT OF ACUTE PANCREATITIS RELATED TO GLP1 RECEPTOR AGONIST

李瑞祥

PD-8

A CASE OF KLEBSIELLA PNEUMONIA LIVER ABSCESS WITH MULTIPLE SEPTIC METASTATIC INFECTIONS

李瑞祥

PD-9

ELEVATED SERUM CYTOKERATIN-18 LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE

張毓泓

PD-10

THE EARLY CHANGES IN AXONAL NEUROPHYSIOLOGY OF AXON IN PRE-DIABETES

江圓

PD-11

PROTECTIVE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKERS ON DIABETIC NEPHROPATHY

吳明諴

PD-12

FACTITIOUS HYPOGLYCEMIA IN TYPE 2 DIABETES PATIENT-A CASE REPORT

林玉怡

PD-13

A CASE REPORT OF IMMUNE CHECK-POINT INHIBITOR INDUCED AUTOIMMUNE DIABETES MELLITUS

黃于玶

PD-14

HISTONE DEACETYLASE INHIBITION OF CARDIAC AUTOPHAGY IN RATS ON A HIGH-FAT DIET WITH LOW DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETES MELLITUS

李亭儀

PD-15

DECREASED RISK OF GINGIVITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS USING CALCIUM CHANNEL BLOCKERS

陳信宏

PD-16

FIRST LINE THERAPY WITH METFORMIN AND PEMETREXED IN TYPE 2 DIABETES WITH ADVANCED LUNG ADENOCARCINOMA

蔡易婷

49

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

題 目

第一作者

PD-17

AUTOIMMUNE POLYENDOCRINE SYNDROMES TYPE 3 PRESENTING WITH SLOWLY PROGRESSIVE TYPE 1 DIABETES MELLITUS , PERNICIOUS ANEMIA AND AUTOIMMUNE THYROID DISEASE: TWO CASE REPORT

許高鳴

PD-18

HYPERDENSE BASAL GANGLIA IN NONKETOTIC HYPERGLYCEMIA WITH STROKE-LIKE PRESENTATION

花士哲

PD-19

RISK OF MORTALITY INCREASES IN DIABETIC NEPHROPATHY IN UREMIA WITHOUT TREATMENT OF ANTI-DIABETIC AGENTS OR INSULIN

吳忠擇

PD-20

BASELINE HBA1C LEVEL AND BODY MASS INDEX PREDICT EFFICACY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS IN TAIWANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS

林毅欣

PD-21

REVIEW OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS INDUCED EU-GLYCEMIC DIABETIC KETOACIDOSIS: POSSIBLE PATHOPHYSIOLOGY AND CONTRIBUTING FACTORS

林毅欣

PD-22

CASE REPORT: THE SAFETY AND EFFICACY OF LIRAGLUTIDE IN PATIENT WITH MITOCHONDRIA DIABETES AND PSORIASIS IN SHORT-TERM USE

黃峻偉

PD-23

CASE REPORT: THE SAFETY AND EFFICACY OF SGLT2 INHIBITOR EMPAGLIFLOZIN IN PATIENT WITH MITOCHONDRIAL DIABETES.

黃峻偉

PD-24

A CASE REPORT: ADVANCED PANCREATIC NEUROENDOCRINE TUMOR WITH PRESENTATION OF EPISODIC HYPOGLYCEMIA

陳怡蓁

PD-25

ASSOCIATION OF DIABETIC KETOACIDOSIS AND GLYCEMIC CONTROL AMONG TYPE 1 DIABETES WITH PREMIX VS BASAL BOLUS INSULIN THERAPY

周威宇

PD-26

REGUATION OF THE GUT–LIVER AXIS BY GLP-1 RECEPTOR AGONIST TO ATTENUATE THE FATTY LIVER

邱馨瑩

PD-27

THE GLUCOSE PATTERN CHANGES BETWEEN PREMIXED AND BASAL-BASED INSULIN THERAPIES IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES MELLITUS

邱雪華

50

Agenda

March 10-11,2018

BP1-3: 廠商論文壁報展示 題 目

投稿單位

BP-1

COMPARABLE GLYCEMIC CONTROL WITH ONCE WEEKLY DULAGLUTIDE VERSUS INSULIN GLARGINE, BOTH COMBINED WITH LISPRO, IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (AWARD-7)

LILLY

BP-2

DULAGLUTDE TREATMENT IS ASSOCIATED WITH LESS EGFR DECLINE AND GREATER REDUCTION IN ALBUMINURIA IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE STAGE 3-4 (AWARD-7)

LILLY

BP-3

STEADY STATE BLOOD GLUCOSE CONTROL FOR ONCE WEEKLY DULAGLUTIDE DURING PEAK AND TROUGH CONCENTRATION DAYS

LILLY

51

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

社團法人中華民國內分泌暨糖尿病學會 第 13 屆第 3 次會員大會暨學術研討會 日期：民國 107 年 3 月 10-11 日／地點：台大醫院國際會議中心

March 10, 2018

PL1: Plenary Lecture 1

【101 Room】 Time 13:20-13:30 PL-1 13:30-14:15

Topic OPENING

Time

Topic

32

Moderator

Yutaka Seino

許惠恒

PL3: Plenary Lecture 3

Time

曾芬郁

許惠恒

PROMOTING DIABETES RESEARCH FOR BETTER DIABETES CARE IN ASIA: FOCUS ON INSULIN SECRETION AND INCRETINS

【101 Room】

PL-3 09:50-10:30

Speaker

OPENING

March 11, 2018

09:45-09:50

Rossella Elisei

PL2:Plenary Lecture 2

【101 Room】

PL-2 14:20-15:00

Moderator 曾芬郁

TARGET THERAPIES IN ADVANCED THYROID CANCER

March 10,2018

14:15-14:20

Speaker

Topic

Speaker

OPENING THYROID CANCER-FROM BEDSIDE TO BENCH

Moderator 林宏達

林仁德

林宏達

Agenda

March 11,2018

PL4: Plenary Lecture 4

【101 Room】 Time

Topic

13:30-13:35 PL-4 13:35-14:15

Speaker

OPENING

Moderator 莊立民

GENETIC MANIPULATION TOWARDS IMMUNE TOLERANCE: APPROACHES

BY TRANSGENIC AND KNOCKOUT/ KNOCKDOWN MOUSE MODELS

司徒惠康

莊立民

DAROC-TADE Joint Symposium

March 10 , 2018 【101 Room】

2018 台灣糖尿病高血脂醫療合併照護及政策 Time

Topic

08:00~08:20

報到

08:20~08:30

OPENING

Speaker Moderator

杜思德

DAROC-TADE1 08:30~09:10

台灣糖尿病高血脂指引之說明

洪晧彰

杜思德

DAROC-TADE2 09:10~09:50

血脂治療新選擇 PCSK9 抑制劑

吳卓鍇

陳榮福

從糖尿病防治暨其合併症談臺灣醫 療整合照護展望

王英偉

蔡世澤

醫學中心到基層醫療健保： 糖尿病疾病照護的未來

李伯璋

李洮俊

09:50~10:00 DAROC-TADE3

0:00~10:50

DAROC-TADE4 10:50~11:40

COFFEE BREAK

11:40~11:50

PANEL DISCUSSION

許惠恒 杜思德

11:50-12:00

CLOSING

許惠恒

33

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 10, 2018 【301 Room】

MTP-1: Meet the Professor-1

Time MTP-1 12:00-13:00

March 10, 2018 【402AB Room】

Topic AUTOIMMUNITY AND THYROID CARCINOMA

March 10, 2018 【301 Room】

Topic CLINICAL MANAGEMENT OF TYPE 2 DIABETES WITH CHRONIC KIDNEY DISEASE IN JAPAN: CURRENT SITUATION AND STRATEGY

Speaker Moderator Abe Masanori

Topic

Speaker Moderator

OPENING GRAVES’ OPHTHALMOPATHY -CLINICAL EXPERIENCES IN KOREA

Jeehee Yoon

SE1-2 15:50-16:10

MEDICAL TREATMENT OF GRAVES’ ORBITOPATHY

施翔蓉

SE1-3 16:10-16:30

THE STRATEGY FOR THE MANAGEMENT OF GRAVES’ OPHTHALMOPATHY

魏以宣

34

莊立民

ESROC and KES Joint Symposium

SE1-1 15:30-15:50

16:30-16:40

張天鈞

SE1: Endocrine Symposium 1

Time 15:20-15:30

Rosella Elisei

MTP-1: Meet the Professor-2

Time MTP-2 17:00-18:00

Speaker Moderator

CLOSING

曾芬郁 Dongsun Kim

Agenda

March 10, 2018 【402CD Room】

SE2: Endocrine Symposium 2

New progress in treatment and diagnosis of thyroid diseases

Time

Topic

Speaker

SE2-1 15:25-15:45

CONTRAST-ENHANCED ULTRASOUND (CEUS) OF THE THYROID GLAND

周宜宏

SE2-2 15:45-16:05

MOLECULAR TESTING IN CYTOLOGICAL INDETERMINATE THYROID NODULES

劉瑞川

SE2-3 16:05-16:25

CURRENT CONCEPT FOR THYROID RADIOFREQUENCY ABLATION

林偉哲

SE2-4 16:25-16:45

NEW APPLICATION OF GENETIC TESTING IN CLINICAL DIAGNOSIS

蘇怡寧

15:20-15:25

16:45-16:50

March 11, 2018 【401 Room】

OPENING

王佩文 陳涵栩

CLOSING

SE3: Endocrine Symposium 3

Taiwan Society of Aldosteronism Joint Symposium

Time

SE3-1

Moderator

Topic

8:00-8:05

OPENING

8:05-8:35

NATIONAL PA REGISTRY-BASED EVIDENCE FOR CLINICAL PRACTICE OF PRIMARY ALDOSTERONISM IN JAPAN

Speaker Moderator

Mitsuhide Naruse 曾芬郁 吳寬墩

SE3-2

8:35-9:05

ADRENAL VENOUS SAMPLING IN NTUH

張晉誠

SE3-3

9:05-9:35

CASE DETECTION AND DIAGNOSIS OF PRIMARY ALDOSTERONISM -THE CONSENSUS OF TAIWAN SOCIETY OF ALDOSTERONISM

胡雅惠

9:35-9:40

PANEL DISCUSSION

吳允升 35

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 11 , 2018 【402 AB Room】

SE4: Endocrine Symposium 4

Thyroid nodules and differentiated carcinoma clinical manual

Time

Topic

Speaker Moderator

8:00-8:05

OPENING

SE4-1

8:05-8:20

從偶發性的甲狀腺結節談起

陳涵栩

SE4-2

8:20-8:35

甲狀腺細針穿刺細胞學檢查

林樹福

SE4-3

8:35-8:50

細胞學檢查後的部份對策

施翔蓉

SE4-4

8:50-9:05

懷孕期間發現的結節處置

蘇登煌

SE4-5

9:05-9:20

分化型甲狀腺癌的術後風險分期與放射性 碘治療

張雁翔

9:20-9:25

CLOSING

March 11 , 2018 【401 Room】

SE5: Endocrine Symposium 5 Pheochromocytoma

Time 14:45-14:50

Topic

Speaker Moderator

OPENING

SE5-1 14:50-15:30

UP-TO-DATE OF CLINICAL PRACTICE OF PHEOCHROMOCYTOMA/ PARAGANGLIOMA

SE5-2 15:30-15:55

GENETICS AND DIAGNOSIS OF PHEOCHROMOCYTOMA/ PARAGANGLIOMA

陳沛隆

SE5-3 15:55-16:20

SURGICAL TREATMENT OF PHEOCHROMOCYTOMA

黃國皓

16:20-16:35 36

陳思達 劉鳳炫

PANEL DISCUSSION

Mitsuhide Naruse

張慶忠

Agenda

March 11 , 2018 【402AB Room】

SE6: Endocrine Symposium 6 Lipid forum

Time 14:45-14:50

Topic

Speaker Moderator

OPENING

SE6-1 14:50-15:15

CURRENT CHALLENGES IN THE TREATMENT OF PATIENTS WITH HYPERLIPIDEMIA

SE6-2 15:15-15:40

PCSK9 INHIBITORS, A NEW THERAPEUTIC REGIMEN FOR PATIENTS WITH DYSLIPIDEMIA- FROM JAPAN’S PERSPECTIVE.

楊偉勛

Masato Odawara 黃天祥 蔡克嵩

SE6-3 15:40-16:05

THE ROLE OF PCSK9 INHIBITORS FOR LDL-C REDUCTION IN DIABETIC PATIENT WITH ASCVD- FROM ENDOCRINOLOGIST POINT OF VIEW

歐弘毅

SE6-4 16:05-16:30

EVIDENCE-BASED PCSK9 INHIBITORS: FROM BENCH TO CLINIC AND ITS PROSPECT

林維文

16:30-16:35

March 10 ,2018 【401Room】

CLOSING

SD1: Diabetes Symposium 1

DM and Geriatric syndrome: Muscle and Brain

Time 15:20-15:25

Topic

Speaker Moderator

OPENING

SD1-1 15:25-16:10

FRAILTY AND SARCOPENIA IN OLDER ADULTS WITH DIABETES MELLITUS

陳亮恭

陳榮福

SD1-2 16:10-16:55

COGNITIVE IMPAIRMENT AND DIABETES: RECIPROCAL RELATIONS AND CLINICAL IMPLICATIONS

王培寧

何橈通

16:55-17:00

CLOSING 37

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 11,2018 【101Room】

SD2: Diabetes Symposium 2

2018 DAROC clinical practice guidelines for diabetes care

Time 08:00-08:05

Topic

Speaker Moderator

OPENING

SD2-1 08:05-08:30

糖尿病照護指引摘要

李弘元

洪乙仁

SD2-2 08:30-08:55

妊娠糖尿病的診斷與治療

郭俊亨

陳清助

SD2-3 08:55-09:20

糖尿病治療的新進展

朱志勳

謝明家

09:20-09:30

March 11,2018 【301 Room】

CLOSING

SD3: Diabetes Symposium 3 Clinical management in diabetes

Time 08:00-08:05

Topic

Speaker Moderator

OPENING

SD3-1 08:05-08:45

ORAL ANTIHYPERGLYCEMIC THERAPY IN T2DM PATIENTS WITH ASCVD – EVIDENCE AND CLINICAL PRACTICE RECOMMENDATIONS

Juliana Chan

杜思德

SD3-2 08:45-09:25

THERAPEUTIC ADVANCES WITH NEW INSULIN ANALOGUE AND GLP-1RA BASED ON RECENT CVOT RESULTS

Masato Odawara

蔡世澤

09:25-09:30

38

CLOSING

Agenda

March 11,2018 【402CD Room】

SD4: Diabetes Symposium 4

Basic research in diabetes and endocrinology

Time 08:00-08:05

Topic

Speaker

Moderator

OPENING

SD4-1 08:05-08:45

PROTECTIVE ROLE OF THYROID HORMONE IN LIVER CARCINOGENESIS

林光輝

莊峻鍠

SD4-2 08:45-09:25

ROLE OF ADIPOCYTE HYPERTROPHY AND HYPOXIA IN THE DEVELOPMENT OF OBESITY-ASSOCIATED ADIPOSE TISSUE INFLAMMATION AND INSULIN RESISTANCE – THE INVOLVEMENT OF COX-2 ACTIVATION

謝博軒

楊偉勛

09:25-09:30

March 11,2018 【101 Room】

CLOSING

SD5: Diabetes Symposium 5

Diabetes and Nervous System: Brain and Peripheral Nerves

Time 14:45-14:50

Topic

Speaker

Moderator

OPENING

SD5-1 14:50:15:35

DIABETIC NEUROPATHY: PERCEPTION Solomon BEYOND THE SEAM OF THE Tesfaye PERIPHERY

黃禹堯

SD5-2 15:35-16:20

GLYCEMIC CONTROL FOR PATIENTS WITH CEREBROVASCULAR DISEASE

戴東原

16:20-16:25

鄭建興

CLOSING

39

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 11,2018 【301 Room】

SD6: Diabetes Symposium 6

Diabetes and Kidney: From Diabetologist’s and Nephrologist’s View

Time

Topic

Speaker

Moderator

SD6-1 14:50:15:35

GROWING CHALLENGE OF DIABETIC NEPHROPATHY

Daisuke Koya

辛錫璋

SD6-2 15:35-16:20

GLUCOSE CONTROL IN DIABETIC PATIENTS WITH MODERATE AND ADVANCED KIDNEY DISEASE

林俊良

許惠恒

14:45-14:50

16:20-16:25

March 10 ,2018 【402AB Room】

OPENING

CLOSING

YL: Young Investigator Research Lecture

Time

YL-1

Topic

Speaker

15:20-15:30

OPENING

15:30-15:50

第 2 型糖尿病小鼠模式腎臟中之前列腺素 E2 代謝產物表現的研究

林志弘 辛錫璋

YL-2

15:50-16:10

母系遺傳粒線體缺損造成胰島素阻抗性之 機轉

張以承

YL-3

16:10-16:30

胰淀素 (AMYLIN) 與新生糖尿病及肥胖的 關係

范綱志

YL-4

40

16:30-16:50

探討 FNDC5/irisin 於高血糖和肥胖之胰臟 內和胰島素分泌與胰島細胞增生之關聯

16:50-17:00

CLOSING

Moderator

黃建寧 吳忠擇

Agenda

AP: 2018 Award

March 11 , 2018

Grant Award Lectures

【402CD Room】 Time 14:45-14:50

Topic

Speaker

Moderator

OPENING 諾華優秀論文獎

AP-1

14:50-15:10

THE HEPATIC PROTECTION EFFECTS OF HEPASSOCIN IN HYPERGLYCEMIC CRISIS

歐弘毅

AP-2

15:10-15:30

EFFICACY OF A HSP90 INHIBITOR, GANETESPIB, IN PRECLINICAL THYROID CANCER MODELS

林樹福

諾和諾德優秀論文獎 AP-3

15:30-15:50

LOWER RISK OF DEMENTIA WITH PIOGLITAZONE, COMPARED WITH OTHER SECOND-LINE TREATMENTS, IN METFORMIN-BASED DUAL THERAPY: A POPULATION-BASED LONGITUDINAL STUDY

盧介祥

AP-4

15:50-16:10

USEFULNESS OF THE PLASMA GLUCOSE CONCENTRATION-TOHBA1C RATIO IN PREDICTING CLINICAL OUTCOMES DURING ACUTE ILLNESS WITH EXTREME HYPERGLYCEMIA.

蘇郁文

16:10-16:20

CLOSING

葉振聲 王治元

41

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The

th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS: Lunch Symposium Room 101

Room 301

Room 401

Room 402AB

Room 402CD

Room 202

Room 203

March 10 12:00-13:00

LS1

LS2

LS3

LS4

LS5

LS6

台灣諾華

台灣禮來

台灣諾華

阿斯特捷利康

諾和諾德

輝瑞

April 9 12:10-13:20

LS7

LS8

LS9

LS10

LS11

LS12

LS13

美敦力

台灣禮來

賽諾菲

默沙東

安斯泰來

亞培

友華

March 10, 2018

Topic

Speaker

Moderator

LS-1

台灣 諾華

JAPAN EXPERIENCE IN MANAGING OLDER T2DM: ROLE OF DPP4I AS THE FIRST LINE THERAPY

Daisuke Koya

胡啟民

LS-2

台灣 禮來

UTILIZING TRULICITY WITH INSULIN: WHAT ARE THE CLINICAL IMPLICATIONS AND HOW DOES THIS HELP OUR PATIENTS

Iain Cranston

許惠恒

LS-3

台灣 諾華

OPTIMIZING THE TREATMENT OF ACROMEGALY PATIENTS WITH 1ST GENERATION SSA AND 2ND GENERATION SSA

張宏猷

陳榮福

LS-4

阿斯特 捷利康

LS-5

LS-6

REDUCING THE BURDEN OF T2DM: Alexander NOVEL MEDICATION BY COMBINATION Tan OF METFORMIN AND SGLT2 INHIBITORS

黃禹堯

諾和 諾德

A PRACTICAL APPROACH FOR BASAL INSULIN TREATMENT WITH CONFIDENCE

楊宜瑱

黃建寧

輝瑞

HIDDEN FACE OF DIABETES: DIABETIC DYSLIPIDEMIA MANAGEMENT AND EVIDENCES OF STATIN IN ASIAN

Juliana Chan

HIDDEN FACE OF DIABETES: WHY SHOULD WE CARE DIABETIC NEUROPATHY AND HOW TO MANAGEMENT 42

Solomon Tesfaye

莊立民

Agenda

March 11, 2018 LS-7

美敦力

TOPIC

Speaker

Moderator

THE BENEFIT OFSMART GUARD INSULIN PUMP FROM CLINICAL PROSPECTIVE

林嘉鴻

羅福松

王治元

蔡世澤

Masato Odawara

曾芬郁

LS-8 台灣禮來 THE HEART OF DIABETES: 百靈佳殷 BASE ON CURRENT T2D TREATMENT 格翰 STRATEGIES AND GUIDELINES LS-9

賽諾菲

ROLE OF NEW BASAL INSULIN ANALOGUE TOUJEO BASED ON CLINICAL STUDY RESULTS AND REAL WORLD EVIDENCE INCLUDING EXPERIENCES IN JAPAN

LS-10

默沙東

BEYOND THE 10 YEARS : WHERE DO DPP-4 INHIBITORS FIT WITHIN TODAY´S TREATMENT PARADIGM FOR PATIENTS WITH TYPE 2 DIABETES

朱志勳

洪乙仁

LS-11

安斯 泰來

IMPROVING CARDIOVASCULAR AND RENAL OUTCOMES IN GOUTHYPERURICEMIA: WHAT SHOULD WE TARGET?

Austin Stack

許惠恒

LS-12

亞培

POTENTIAL ROLE OF POC A1C TESTING IN PRACTICE

朱芳業

羅世慧

謝明家

陳榮福

LS-13

友華

THE BENEFITS OF HIGH INTENSITY STATIN TREATMENT - FROM REAL-CAD STUDY

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March 10, 2018 【401 Room】 Time

OE: Oral Presentation-Endocrine Topic

Speaker Moderator

OE-1

17:00-17:10

THE SYNERGISTIC EFFECT OF RENALASE AND CHRONIC KIDNEY DISEASE ON ENDOTHELIN-1 IN SUBJECTS WITH ESTABLISHED CORONARY ARTERY DISEASE A CROSS-SECTIONAL STUDY

李宇璇

OE-2

17:10-17:20

TREATMENT EFFICACY AND SAFETY OF ULTRASOUND-GUIDED PERCUTANEOUS RADIOFREQUENCY ABLATION FOR BENIGN THYROID NODULES: KCGMH EXPERIENCE

林偉哲

OE-3

17:20-17:30

LOW-DOSE ADEFOVIR THERAPY RELATED OSTEOMALACIA MIMICKING MULTIPLE BONE METASTASIS - A CASE SERIES STUDY

劉仕朋 簡銘男 李亭儀

OE-4

17:30-17:40

A NOVEL MISSENSE MUTATION OF THE MEN1 GENE IN CHINESE FAMILY WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 1

梁博智

OE-5

17:40-17:50

EXPERIENCE OF IODINE-131 METAIODOBENZYLGUANIDINE THERAPY OF MALIGNANT PHEOCHROMOCYTOMA IN CCH

林思涵

OE-6

17:50-18:00

GENETIC STUDY FOR COMBINED PITUITARY HORMONE DEFICIENCY IN TWO SIBLINGS

溫緯倫

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Agenda

March 10, 2018 【301 Room】 Time

OD: Oral Presentation-Diabetes Topic

Speaker Moderator

OD-1

17:00-17:10

ADAM10 MODULATES CALCITRIOLREGULATED RAGE IN CARDIOMYOCYTES

李亭衛

OD-2

17:10-17:20

THE CHANGE OF THE BONE STRUCTURE AND MICROARCHITECTURE AFTER ORAL ANTIDIABETIC DRUG TREATMENT IN DIET-INDUCED OBESITY MICE

曹政峰

OD-3

17:20-17:30

CHANGES OF GUT MICROBIOTA IN NEWLY-DIAGNOSED TYPE 2 DIABETES TREATED WITH METFORMIN MONOTHERAPY

洪薇雯

OD-4

17:30-17:40

LEVELS OF SERUM HIGH MOBILITY GROUP BOX 1 WERE INDEPENDENTLY ASSOCIATED WITH CARDIOVASCULAR RISK IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY

王俊興 李建興 林昆德

OD-5

17:40-17:50

EVALUATION OF GLYCEMIC CONTROL AND SELF-EFFICACY AMONG PATIENTS RECEIVING CONTINUOUS GLUCOSE MONITORING WITH IMMEDIATE COUNSELING FEEDBACK COMPARED WITH DELAYED COUNSELING FEEDBACK

杜業豐

OD-6

17:50-18:00

PREVALENCE, INCIDENCE, AND RISK FACTORS OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES - AN 8-YEAR PROSPECTIVE COHORT STUDY IN A COMMUNITY HOSPITAL

許志成

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March 10-11,2018

PE: Poster Presentation-Endocrine 主持人： 吳婉禎、蘇登煌、邱偉益 題 目

第一作者

PE-1

REPETITIVE SEIZURE AS THE INITIAL PRESENTATION IN A PATIENT WITH PSEUDOHYPOPARATHYROIDISM: A CASE REPORT

于念主

PE-2

CATECHOLAMINE - INDUCED CARDIOMYOPATHY IN A 37 YEAR-OLD WOMAN WITH INITIAL PRESENTATION AS CARDIOGENIC SHOCK

林榆培

PE-3

HYPOTHYROIDISM WITH HIGH LEVEL OF FT4

韋佳齡

PE-4

UNDERWEIGHT INCREASES THE RISK OF EARLY DEATH IN TUBERCULOSIS PATIENTS: A POPULATION-BASED STUDY

顏永豐

PE-5

A VERY RARE CASE OF PULMONARY LYMPHANGITIC CARCINOMATOSIS IN PATIENT WITH RECURRENT PAPILLARY THYROID CARCINOMA

黃則穎

PE-6

PITUITARY PLURIHORMONAL ADENOMA SECRETING TSH AND ALH –A CASE REPORT

林玉怡

PE-7

PARATHYROID ADENOMA PRESENTED WITH HYPOCALCEMIA IN A PATIENT WITHOUT CHRONIC RENAL INSUFFICIENCY

林軒維

PE-8

THYROID MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA IN A 63-YEAR-OLD WOMAN : A CASE REPORT

王新瑋

PE-9

131I ABLATION THERAPY IN PATIENT WITH THYROID CANCER AND ESRD ON HEMODIALYSIS: CASE REPORT

王志仁

PE-10

BILATERAL ADRENAL GLAND HEMORRHAGE: A CASE REPORT AND REVIEW OF THE LITERATURE

陳永年

PE-11

DECIPHERING THE REGULATORY CODE OF THE RELATIONSHIP BETWEEN THE CHOLINE TRIMETHYLAMINE LYASE (CUTC) AND CARDIOVASCULAR DISEASES

李明彰

46

Agenda

題 目

第一作者

PE-12

LONG-TERM THERAPEUTIC OUTCOME OF PAPILLARY THYROID CARCINOMA WITH HYPERPARATHYROIDISM: A CASE-CONTROL STUDY

蔡之祐

PE-13

CASE REPORT: HYPERTROPHIC OSTEOARTHROPATHY IN 21 YEARS OLD YOUNG MAN

陳威麟

PE-14

ACROMESOMELIC DYSPLASIA MAROTEAUX TYPE WITH VITAMIN D DEFICIENCY -A CASE REPORT

林玉怡

PE-15

HUGE PARATHYROID MASS WITH HYPERCALCEMIC CRISIS: A CASE REPORT

謝寶龍

PE-16

LITHIUM-INDUCED HYPOTHYROIDISM: A CASE REPORT

楊晉州

PE-17

COMPUTER-AIDED DIAGNOSTIC TECHNIQUE IN FDG POSITIVE THYROID NODULE– A CLINICAL EXPERIENCE OF 73 NON-THYROID CANCER PATIENTS

林怡瑄

PE-18

PARAGANGLIOMA AT CAROTID BIFURCATION PRESENTING AS CAROTID BODY TUMOR, COEXISTENCE WITH PAPILLARY THYROID CARCINOMA: A DIAGNOSIS DILEMMA

PE-19

GRAVES’ DISEASE COMPLICATED WITH HASHIMOTO ENCEPHALOPATHY: A CASE REPORT AND REVIEW OF LITERATURE

花士哲

PE-20

THYROID CANCER PRESENTED WITH AN INTERRUPTED PERIPHERAL CALCIFICATION IN SONOGRAPHY —A CASE REPORT

徐維信

PE-21

A CASE REPORT OF CUSHING DISEASE RELATED MULTISYSTEM FAILURE.

潘筱芳

PE-22

THE EFFECT OF THYROXINE SUPPRESSION THERAPY ON GOITER SIZE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN

陳瓊雅

PE-23

STEMNESS ACTIVATION IN ADRENAL CORTICOMEDULLARY MIXED TUMOR STUDIED BY WHOLE EXOME SEQUENCING

邱馨瑩

PE-24

CLINICAL SIGNIFICANCE OF HEPATIC I-131 UPTAKE IN THYROID CANCER

李宜螢

周璠

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題 目

第一作者

PE-25

FALSELY HIGH RESULTS IN MULTIPLE HORMONE IMMUNOASSAYS – A CASE REPORT

徐惠娟

PE-26

CLINICOPATHOLOGICAL FEATURES OF PAPILLARY THYROID CARCINOMA PATIENTS WITH POSITIVE BRAF V600E MUTATION: SINGLE CENTER EXPERIENCE IN TAIWAN

姜和均

PE-27

METASTATIC POORLY DIFFERENTIATED THYROID CARCINOMA ARISING IN STRUMA OVARII WITH COEXISTENCE OF GRAVES` DISEASE AND MICROPAPILLARY THYROID CARCINOMA

謝雅湄

PE-28

SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR PREDICTING REDUCTION IN PULSE PRESSURE AFTER A ONEHOUR REST IN NURSES WORKING NIGHT SHIFTS

李奕德

PE-29

HEPATOTOXICITY OF PROPYLTHIOURACIL (PTU) IN A BOY WITH GRAVES DISEASE

李燕晉

March 10-11,2018

PD: Poster Presentation-Diabetes 主持人：李奕德、朱志勳、王俊興、李弘元 題 目

第一作者

PD-1

MATERNAL AND FETAL OUTCOMES OF PREGNANT WOMEN WITH TYPE 1 DIABETES, A NATIONAL POPULATION STUDY

林樹福

PD-2

TPL2 (THERAPEUTIC TARGETING TUMOR PROGRESSION LOCUS-2)/ATF4 (ACTIVATING TRANSCRIPTION FACTOR-4)/ SDF1Α (CHEMOKINE STROMAL CELL-DERIVED FACTOR-Α) AXIS SUPPRESSES DIABETIC RETINOPATHY

賴德偉

PD-3

HIGH GLUCOSE VARIABILITY INCREASES RE-ADMISSION RATES WITHIN 30 DAYS OF DISCHARGE IN DEPARTMENT OF SURGERY

謝靜蓉

PD-4

EFFECT OF GLP-1 RECEPTOR AGONIST ON PATIENTS WITH TYPE 2 DIABETES IN REAL PRACTICE: EXPERIENCE FROM A REGIONAL HOSPITAL

汪偉建

48

Agenda

題 目

第一作者

PD-5

EMPAGLIFLOZIN REPLACEMENT FOR DIPEPTIDYL PEPTIDASE-4 INHIBITORS IMPROVES GLYCATED HEMOGLOBIN IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES

黃瓊慧

PD-6

ASSOCIATION BETWEEN SERUM BILIRUBIN LEVELS AND PROGRESSION OF ALBUMINURIA IN TAIWANESE WITH TYPE 2 DIABETES MELLITUS

陳維健

PD-7

A CASE REPORT OF ACUTE PANCREATITIS RELATED TO GLP1 RECEPTOR AGONIST

李瑞祥

PD-8

A CASE OF KLEBSIELLA PNEUMONIA LIVER ABSCESS WITH MULTIPLE SEPTIC METASTATIC INFECTIONS

李瑞祥

PD-9

ELEVATED SERUM CYTOKERATIN-18 LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE

張毓泓

PD-10

THE EARLY CHANGES IN AXONAL NEUROPHYSIOLOGY OF AXON IN PRE-DIABETES

江圓

PD-11

PROTECTIVE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKERS ON DIABETIC NEPHROPATHY

吳明諴

PD-12

FACTITIOUS HYPOGLYCEMIA IN TYPE 2 DIABETES PATIENT-A CASE REPORT

林玉怡

PD-13

A CASE REPORT OF IMMUNE CHECK-POINT INHIBITOR INDUCED AUTOIMMUNE DIABETES MELLITUS

黃于玶

PD-14

HISTONE DEACETYLASE INHIBITION OF CARDIAC AUTOPHAGY IN RATS ON A HIGH-FAT DIET WITH LOW DOSE STREPTOZOTOCIN-INDUCED TYPE 2 DIABETES MELLITUS

李亭儀

PD-15

DECREASED RISK OF GINGIVITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS USING CALCIUM CHANNEL BLOCKERS

陳信宏

PD-16

FIRST LINE THERAPY WITH METFORMIN AND PEMETREXED IN TYPE 2 DIABETES WITH ADVANCED LUNG ADENOCARCINOMA

蔡易婷

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題 目

第一作者

PD-17

AUTOIMMUNE POLYENDOCRINE SYNDROMES TYPE 3 PRESENTING WITH SLOWLY PROGRESSIVE TYPE 1 DIABETES MELLITUS , PERNICIOUS ANEMIA AND AUTOIMMUNE THYROID DISEASE: TWO CASE REPORT

許高鳴

PD-18

HYPERDENSE BASAL GANGLIA IN NONKETOTIC HYPERGLYCEMIA WITH STROKE-LIKE PRESENTATION

花士哲

PD-19

RISK OF MORTALITY INCREASES IN DIABETIC NEPHROPATHY IN UREMIA WITHOUT TREATMENT OF ANTI-DIABETIC AGENTS OR INSULIN

吳忠擇

PD-20

BASELINE HBA1C LEVEL AND BODY MASS INDEX PREDICT EFFICACY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS IN TAIWANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS

林毅欣

PD-21

REVIEW OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS INDUCED EU-GLYCEMIC DIABETIC KETOACIDOSIS: POSSIBLE PATHOPHYSIOLOGY AND CONTRIBUTING FACTORS

林毅欣

PD-22

CASE REPORT: THE SAFETY AND EFFICACY OF LIRAGLUTIDE IN PATIENT WITH MITOCHONDRIA DIABETES AND PSORIASIS IN SHORT-TERM USE

黃峻偉

PD-23

CASE REPORT: THE SAFETY AND EFFICACY OF SGLT2 INHIBITOR EMPAGLIFLOZIN IN PATIENT WITH MITOCHONDRIAL DIABETES.

黃峻偉

PD-24

A CASE REPORT: ADVANCED PANCREATIC NEUROENDOCRINE TUMOR WITH PRESENTATION OF EPISODIC HYPOGLYCEMIA

陳怡蓁

PD-25

ASSOCIATION OF DIABETIC KETOACIDOSIS AND GLYCEMIC CONTROL AMONG TYPE 1 DIABETES WITH PREMIX VS BASAL BOLUS INSULIN THERAPY

周威宇

PD-26

REGUATION OF THE GUT–LIVER AXIS BY GLP-1 RECEPTOR AGONIST TO ATTENUATE THE FATTY LIVER

邱馨瑩

PD-27

THE GLUCOSE PATTERN CHANGES BETWEEN PREMIXED AND BASAL-BASED INSULIN THERAPIES IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES MELLITUS

邱雪華

50

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March 10-11,2018

BP1-3: 廠商論文壁報展示 題 目

投稿單位

BP-1

COMPARABLE GLYCEMIC CONTROL WITH ONCE WEEKLY DULAGLUTIDE VERSUS INSULIN GLARGINE, BOTH COMBINED WITH LISPRO, IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (AWARD-7)

LILLY

BP-2

DULAGLUTDE TREATMENT IS ASSOCIATED WITH LESS EGFR DECLINE AND GREATER REDUCTION IN ALBUMINURIA IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE STAGE 3-4 (AWARD-7)

LILLY

BP-3

STEADY STATE BLOOD GLUCOSE CONTROL FOR ONCE WEEKLY DULAGLUTIDE DURING PEAK AND TROUGH CONCENTRATION DAYS

LILLY

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PL-1

TARGET THERAPIES IN ADVANCED THYROID CANCER ROSSELLA ELISEI Associate Professor of Endocrinology, University of Pisa

Thyrosine kinase inhibitors (TKI) are nowadays the new drugs involved in the therapy of advanced and progressive thyroid cancer (MTC). Four of them, have been approved by both FDA and EMA for this purpose: lenvatinib and sorafenib for dedifferentiated thyroid cancer (papillary and follicular [PTC and FTC]) and vandetanib and cabozantinib for medullary thyroid cancer (MTC). As well known, TKI are cytostatic drugs that are able to block the activities of several tyrosine kinases including BRAF and RET which are the major players in the pathogenesis of both PTC/FTC and MTC. For this reason TKI must be used when there is an evident progression of the metastatic disease with the intent to block this progression. A significant increase of the serum markers, such as thyroglobulin and calcitonin, can suggest that the disease is in progression but only after a documented radiological progression according to RECIST, the TKI will be prescribed. However, all the phase III clinical trials, SELECT (for lenvatinib), DECISION (for Sorafenib), ZETA (for vandetanib) and EXAM (for cabozantinib), showed that these drugs are also able to determine a shrinkage of the lesions with a relevant objective response rate (ORR). On the basis of this objective results they can be also used with the purpose to reduce the size of lesions whose location can be dangerous for the life of our patients such as vertebral lesions that, if growing more, can rapidly compress the spinal cord determing para- or tetraplegia. Moreover, anytime there is a single lesion that is progressing or representing a clinical problem for our patient, the possibility of a local treatment, such as external radiotherapy, laser ablation, chemoembolization ecc, should be considered. Finally, anytime we decide to prescribe a TKI, the possible side effects of the drug, that are very similar among all TKI but with some peculiarities for each drug, must be considered. A very accurate, and possibly multidisciplinary, evaluation of the general health conditions and the other co-morbidities of the patient must be done before starting the systemic TKI therapy.

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Abstract PL-2

PROMOTING DIABETES RESEARCH FOR BETTER DIABETES CARE IN ASIA: FOCUS ON INSULIN SECRETION AND INCRETINS YUTAKA SEINO Director for Kansai Electric Power Hospital, Osaka, Japan; and Director General for Kansai Electric Power Research Institute, Kobe, Japan

The global epidemic of diabetes is a serious medical and social problem in all parts of the world including East and Southeast Asia, which have the highest prevalence of the disease. Type 2 diabetes in East and Southeast Asia is characterized primarily by non-obese and b-cell dysfunction; the pathological manifestation in Europe and North America is generally insulin resistance with obesity.

These differences have an immense impact on anti-diabetes prevention and treatment strategies in different populations.

Incretin-based anti-diabetic strategies including DPP-4 inhibitors (DPP4i) and GLP-1 receptor agonists (GLP-1RA) have been gaining much attention in the management of type 2 diabetes across Asia. The incretins GIP and GLP-1 are released from the gut in response to dietary nutrientsstimulate insulin secretion in a glucose-dependent manner. Meta-analyses of clinical trials on DPP4i and GLP1RA have found the drugs to be more effective in Asian patients, likely due to amelioration of b-cell dysfunction by incretins. We have recently found a potential link between dietary habits and efficacy of DPP4i. The HbA1c-lowering effect of DPP4i is attenuated by intake of saturated fats (SF), possibly because SF enhance GIP secretion and facilitate fat deposition in collaboration with GIP. Since SFconsumption is less in Asia in general compared to Europe and North America, the greater efficacy of DPP4i in Asians may therefore be partly due to dietary habits. We also succeeded in establishing incretin-based diet therapy focusing on meal sequence that ameliorates postprandial glucose elevation often found in Asians. Eating fish before rice was found to enhance GLP-1 secretion and ameliorate postprandial glucose excursion by increasing insulin secretion and delaying gastric emptying, compared to eating fish after rice. Similar reversal of rice and meat, which is rich in SF that enhance not only GLP-1 but also GIP, had similar beneficial effects but facilitated fat accumulation. Thus, the meal sequence, fish before rice, might also enhance HbA1c-lowering effects of DPP4i.

Through my career as diabetologist, I realized importance of our own research activities to understand the pathophysiology of type 2 diabetes in Asians; and to develop diet and exercise therapies as well as pharmacological interventions suitable for the management of Asian type 2 diabetes.

Together with international colleagues, we established the Asian Association for the Study of Diabetes (AASD) in 2009 as a platform for active discussion of diabetes in Asia. By now, AASD has expanded rapidly, with more than 22 diabetes-related member associations across Asia and more than 3,000 individual membership globally. Furthermore, the Journal of Diabetes Investigation (JDI), which was 53

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launched as the AASD official journal in 2010, has been receiving much attention as evidenced by its recent impact factor 3.039. By forming an alliance with international diabetes-related organizations including IDF, the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA), AASD is dedicated to improving diabetes education and care to scientifically to fight against diabetes.

In this lecture phenotype of Asian type 2 diabetes and anti-diabetes strategies for Asian type diabetes will be discussed from incretin perspectives.In addition, I will also discuss need for our diabetes research activities from AASD perspectives.

54

Abstract PL-3

THYROID CANCER-FROM BEDSIDE TO BENCH JEN-DER LIN Division of Endocrinology & Metabolism, Chang Gung Memorial Hospital in Linkou

Thyroid cancer is the most common endocrine disease, with a continuously increasing incidence in both developed and developing countries, including Taiwan. Papillary and follicular thyroid cancer account for 80–90% of the total cases and commonly originate from well-differentiated thyroid follicular cells. In the past 40 years, 4,458 thyroid cancer patients were diagnosed with thyroid cancer and underwent long-term follow-up at Chang Gung Memorial Hospital in Linkou. The clinical characteristics of well-differentiated thyroid cancer may range from indolent papillary microcarcinoma to papillary and follicular thyroid cancer with bone metastases having a poor prognosis. In this study, after a mean follow-up of 10.1 years, the disease-specific mortality (DSM) rate for papillary thyroid carcinoma with distant metastases was 70.0%. Elderly and male patients with papillary thyroid carcinoma (PTC) with distant metastasis were required more aggressive treatment. To identify novel PTC biomarkers, we herein used a GeLC-MS/MS strategy to analyze the proteome profiles of serumabundant-protein-depleted fine-needle aspirated cystic fluids in benign and PTC patients, as well as two PTC cell line secretomes. Comparative analysis revealed that 191 proteins were detected in the PTC, but none in benign cystic fluid samples, and thus may represent as potential PTC biomarkers.

Immunoblot analysis confirmed the elevated expression levels of five proteins (NPC2, CTSC, GPNMB, DPP4, and ERAP2) in PTC versus benign cystic fluids. Immunohistochemical studies of nearly 100 pairs of PTC tissues and their corresponding non-tumor counterparts further showed that AGRN (n = 98), CTSC (n = 99), ERAP2 (n = 98), and GPNMB (n = 100) were significantly (p < 0.05) overexpressed in PTC, and higher expression levels of AGRN and CTSC were also significantly associated with metastasis and poor prognosis in PTC patients. In recent study, we evaluated whether the number of circulating tumor/circulating epithelial cells (CECs) expressing either epithelial cell adhesion molecule (EpCAM), podoplanin (PDPN), or thyroid-stimulating hormone receptor (TSHR) is related to remission and DSM in patients with thyroid cancer. The EpCAM+-CEC, TSHR+-CEC, and PDPN+-CEC counts in the non-remission group (n = 43) were significantly higher than the remission group (n = 85) (p < 0.001). Receiver operating characteristic (ROC) analysis showed that EpCAM+CEC, TSHR+-CEC, and PDPN+-CEC counts distinguished the mortality and survival statuses. In conclusion, new biomarkers for various thyroid cancers may improve the preoperative diagnosis. Early detection of well-differentiated thyroid carcinoma with distant metastasis and DSM may improve therapeutic outcomes.

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Main related references: 1. Jen-Der Lin, Chao-Chun Huang, Hsiao-Fen Weng, Shin-Cheh Chen, Long-Bin Jeng: Comparison of cellular proteins from benign and malignant human thyroid tissues by twodimensional polyacrylamide gel electrophoresis. J Chromatogr 667: 153-60, 1995.

2. Jen-Der Lin, Tzu-Chieh Chao, Hsiao-Fen Weng, Hong-So Huang, Yat-Sen Ho: Establishment of xenografts and cell lines from well differentiated human thyroid carcinoma. J Surg Oncol 63: 112-8, 1996.

3. Jen-Der Lin, Bie-Yu Huang, Hung-Yu Chang: Clinical experience in the diagnosis of 127 papillary thyroid microcarcinomas. Endocr-Relat Cancer 5: 239-45, 1998.

4. Jen-Der Lin, Bie-Yu Huang: Comparison of the results of diagnosis and treatment between solid and cystic well differentiated thyroid carcinomas. Thyroid 8: 661-7, 1998.

5. Jen-Der Lin: The role of apoptosis in autoimmune thyroid disorders and thyroid cancer. Brit Med J 322: 1525-7, 2001.

6. Jen-Der Lin, Tzu-Chieh Chao, Shuo-Chi Chou, Chuen Hsueh: Papillary thyroid carcinomas with lung metastases. Thyroid 14: 1091-6, 2004.

7. Jen-Der Lin, Szu-Tah Chen, Tzu-Chieh Chao, Chuen Hsueh, Hsiao-Fen Weng: Diagnosis and therapeutic strategy of papillary thyroid microcarcinoma. Arch Surg 140:940-5, 2005.

8. Jen-Der Lin, Kun-Ju Lin, Tzu-Chieh Chao, Chuen Hsueh, Ngan-Ming Tsang: Therapeutic outcome of papillary thyroid carcinoma advance than T1N0M0. Radiother Oncol 89: 97-104, 2008.

9. Jen-Der Lin, Shu-Fu Lin, Szu-Tah Chen, Chuen Hsueh, Chia-Lin Li, Tzu-Chieh Chao: Longterm follow-up of papillary and follicular thyroid carcinomas with bone metastasis. PLoS One Mar. 9;12(3):e0173354. doi: 10.1371/journal.pone.0173354, 2017.

10. Hung-Chih Lin, Miaw-Jene Liou, Hsung-Ling Hsu, Jason Chia-Hsun Hsieh, Yi-An Chen, Ching-Ping Tseng, Jen-Der Lin: Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma.

Oncotarget 2016;7(13):17242-53.

11. Ching-Ping Tseng, Kong-Kit Leong, Miaw-Jene Liou, Hsung-Ling Hsu, Hung-Chih Lin, Yi-An Chen, Jen-Der Lin: Circulating epithelial cell counts for monitoring the therapeutic outcome of papillary thyroid carcinoma. Oncotarget 2017, Vol. 8, (No. 44), pp: 77453-77464

56

Abstract PL-4

GENETIC MANIPULATION TOWARDS IMMUNE TOLERANCE: APPROACHES BY TRANSGENIC AND KNOCKOUT/KNOCKDOWN MOUSE MODELS HUEY-KANG SYTWU National Health Research Institutes, Taiwan, ROC

Insulin-dependent diabetes mellitus (IDDM) is a T cell-mediated autoimmune disease. To delineate the protective roles of some immune modulatory molecules, such as soluble decoy receptor 3 (DcR3), cytotoxic T lymphocyte antigen 4 (CTLA4), program death ligand 1 and 2 (PD-L1 and 2), heme oxygenase 1 (HO-1), and chemokine receptor D6 in the autoimmune process and to search for potential preventive and/or therapeutic targets in this disease, we have generated (a) insulin promoter (pIns)-sDcR3 transgenic non-obese diabetic (NOD) mice, (b) pIns-single chain anti-CTLA4 transgenic NOD mice, (c) pIns-single chain anti-4-1BB transgenic NOD mice, (d) pIns-PD-L1 transgenic NOD mice, (e) pIns-HO-1 transgenic NOD mice, and (f) pIns-D6 transgenic NOD mice and demonstrated their immunomodulatory potential and underlying mechanisms. Meanwhile, to explore the modulatory potential of interleukin-12, 23 and 27 on autoimmune diabetes, we have generated following transgenic, knockout and knockdown NOD mice: (1) Th1 and Th2 doubly transgenic (2) IL-12 knockout (3) IL-23 knockdown (4) IL-27 knockdown NOD mice. Our results revealed that 20% IL-12deficient NOD mice still developed autoimmune diabetes, the diabetic incidence of IL-23 knockdown NOD mice is lower than that of control littermates, and the number and percentage of Th1 cells are dramatically decreased and Th17 cells are increased in IL-27 knockdown mice, indicating a differential role of IL-12 cytokine family in modulating Th1 and Th17 cell development during autoimmune diabetogenic process. Making full use of these unique mouse strains, we are quantitatively and qualitatively investigating the immunopathogenic mechanisms of autoimmune diabetes and providing valuable information for the development of novel immunotherapies.

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DAROC-1

RECOMMENDATIONS FOR DIABETES MELLITUS FROM TAIWAN LIPID GUIDELINES HAO-CHANG HUNG Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan,, Taiwan, ROC

Diabetes mellitus refers to a group of metabolic disorders characterized by the presence of hyperglycemia that results from insulin deficiency, insulin resistance, or both. Chronic hyperglycemia is associated with both microvascular and macrovascular complications. Intensive glycemic control reduces the risk of microvascular complications, but its effect on reducing macrovascular complications is less clear.

Diabetic patients are frequently associated with dyslipidemia and atherosclerotic cardiovascular diseases. Diabetic dyslipidemia is featured with increased serum triglyceride, increased VLDL, decreased HDL-C, and increased small dense LDL-C. The risk of cardiovascular disease appears early in the course of dysglycemia and correlates with plasma glucose level.

Aggressive management for lipid disorder and other risk factors has been proven to reduce macrovascular complications in these patients. Comprehensive assessment and treatment of dyslipidemia in diabetic patients are recommended, and it may be prudent to apply the same principles to prediabetic patients as well. Intensive lifestyle intervention is simple and cost-effective and should always be incorporated into dyslipidemia treatment plans.

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Abstract DAROC-2

PCSK9, A NEW SOLUTION TO LIPID TREATMENT CHO-KAI WU Department of Cardiology, National Taiwan University Hospital, Taiwan, ROC

Statins have established strong evidences of efficacy in LDL-C reduction, which is related to prevent patients away from CVD events. PCSK9 inhibitors, a novel lipid lowering therapeutic choice, dramatically lower plasma LDL levels by increasing LDL receptor number within hepatocyte cell membranes. LDL-C receptor (LDL-C R) help on clearance of LDL-C in plasma, which is considered as one of cholesterol regulation mechanism. However,PCSK9 binds to LDL-C R and that reduces the usage of LDL-C R recycle within hepatocyte. PCSK9i inhibits PCSK9 and avoids the decreased recycle usage of LDL-C R. Statin reduces the cholesterol production, however, PCSK9i increases the clearance of LDL-C in plasma, that will help to lower LDL-C level. This novel therapeutic choice also help to reduce the LDL-C level in patients with familial hypercholesterolemia (FH), include HoFH and HeFH, those who have significant higher lipid profile and always lead to CVD in early age. FH is considered as a inherit disease, gene mutation results in cholesterol regulation function loss. In current practice, patients receive high intensity statin at tolerated dose. Ezetimibe is also considered if patients require aggressive LDL-C reduction.

PCSK9i can be considered for statin intolerant population (SI). Fewer medication can be applied for this group of patients. Increased number of scientific evidence showed the efficacy of PCSK9i in LDL-C reduction for different types of patients, including ASCVD, HoFH, HeFH and SI. Over 60% additional LDL-C reduction is predictable when add to original therapy The multi-channel model, but not the conventional model, may explain how statins and PCSK9 inhibitors can produce sustained increases in LDL receptor number.

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DAROC-3

從糖尿病防治暨其合併症談臺灣醫療整合照護展望 王英偉 衛生福利部國民健康署 署長

世界衛生組織 (WHO) 2017 年公布非傳染性疾病 (NCD) 每年全球造成 1,500 萬人死亡，而四 大非傳染疾病 ( 癌症、糖尿病、心血管疾病、慢性呼吸道疾病 ) 約占死亡人數 6 成，吸菸、身體 活動不足、不健康飲食及有害使用酒精為其四大共同危險因素。目前全世界有 4 億 2,000 萬人罹 患糖尿病，在臺灣，糖尿病是國人十大死因第 5 位，2016 年因糖尿病死亡的人數達 9,960 人。依 據 2013-2016 年「國民營養健康狀況變遷調查」發現，18 歲以上國人糖尿病盛行率為 11.5%，粗 估全國約有 222 萬名糖尿病友，而糖尿病病人 5 年內發生心臟病的風險是一般人的 1.5 倍、中風 風險為 2.9 倍、腎臟疾病風險為 2.4 倍，若未良好控制血糖，糖尿病及其合併症將嚴重危害國人 健康。 為提升糖尿病之照護品質，國民健康署積極形塑各場域健康環境，落實民眾養成健康生活型 態知能，並提供成人預防保健服務，及早發現高血糖個案以提供介入服務；在糖尿病照護方面則 結合公共衛生部門、臨床醫療團隊及地方縣市政府等，於全國 22 縣市全面推動糖尿病共同照護 網，建構醫師、護理、營養等跨專業團隊，提升糖尿病品質照護，迄今已完成 9,366 人認證。同 時成立 255 家糖尿病健康促進機構及 176 家腎臟病健康促進機構，機構涵蓋了 6 成以上糖尿病病 人。此外，配合健保署「糖尿病品質支付服務」，藉由跨專業服務提升個案糖尿病照護品質。截 至 2016 年糖尿病照護涵蓋率為 46%，每年仍以 3% 成長率成長中。 由於醫療保險支付制度仍以單一疾病分類為主，而糖尿病病人病程與疾病嚴重度複雜，若未 良好控制血糖則會發生大血管、小血管病變，造成嚴重合併症，研究發現糖尿病導致腎病變及洗 腎個案發生率為 45%。爰此，健康署發展以病人為中心之連續性整合照護模式，除在初級預防積 極營造健康環境，強化民眾健康生活型態。在次級預防則落實各式檢查，包括透過成人預防保健 服務，早期發現糖尿病，並在糖尿病前期即予以介入，針對不同程度的糖尿病研擬提供適當的個 人化介入及衛教措施，延緩糖尿病或其合併症發生。在疾病診療及照護上除持續推動糖尿病共同 照護模式，結合健保署以支付誘因鼓勵提供跨專業團隊服務外，強化基層照護服務量能是刻不容 緩的，如何提升基層院所的照護涵蓋率，以符合病人實際的就醫行為，並落實分級照護，這是跨 司署須共同合作處理的重點。另外透過醫病共享決策模式，提升病人及其家屬的照護健康識能， 加強病人參與自我照護之能力，使其能真正參與疾病照護。目前本署正透過試辦計畫，針對糖尿 病合併有 3a 前期慢性腎臟病或其他合併症的病人，藉由提醒臨床醫師加強其對病人之用藥、生 活型態改善等介入措施，發展多重慢性病管理，延緩疾病或合併症發生。期能透過病人參與之連 續性照護，降低醫療經濟之負荷，進而提升個案生活及照護之品質。

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Abstract DAROC-4

THE HEALTH CARE INSURANCE FROM MEDICAL CENTER TO CLINIC SECTOR: THE FUTURE OF DIABETES CARE PO-CHANG LEE National Health Insurance Administration, Ministry of Health and Welfare, Taiwan

According to the IDF Diabetes Atlas Eighth Edition, the global prevalence of diabetes will reach 629 million by 2045. A survey conducted by the Health Promotion Administration in 2013-2015 indicates that the prevalence of diabetes in adults aged over 18 years in Taiwan reaches 11.8%.The number of people living with diabetes has exceeded 2.27 million. Diabetes not only lead to several of serious complications, deteriorate the quality of life, but also rank top five of leading causes of death in Taiwan in recent years. Meanwhile, the burden of treatment and disease management has been substantially increased. However, the diabetes-related complications can be prevented and delayed disease progression through regular follow-up, active control and effective treatment. Therefore, the prevention and treatment of diabetes are important issue in Taiwan.

Pay for performance(P4P) payment model has been advocated as an alternative in many countries recently, while Fee-for-service (FFS) is lack to provide the incentive of improving quality of care.

However, quality of care which represents the performance is hard to measure precisely. The difference in disease progression and patient’s characteristics influence the outcome of quality surveillance.

Therefore, the main concept of developing P4P in Taiwan is improving the effectiveness and efficiency of disease care to conform the principle of Cost-effectiveness. Focus on diseases which are high expenditure, large population and have room for improvement. To provide financial incentive by paying for care performance, the government has budgeted special fund for P4P implementation from 2001. The special fund which is exclusively used for promoting P4P programs in 2017 is 1.7 billion, for example. At present, the following nine projects have been implemented: Diabetes, Asthma, Breast Cancer, Schizophrenia, Hepatitis B and C Carriers, Early chronic kidney disease, Early Intervention, full-term care of pregnant women and COPD. The NHIA implemented ‘ The Pay for Performance Program for Diabetes ‘ in 2001, combining ’shared care’ and ‘pay for performance’ mechanism. To provide an integrated care for Diabetes patient, the health care institutions should form “team care system”, including physicians, nurses, dietitians, health staff, and team members who need regular continuing education training. Also, the institutions must establish a complete, rational and structured standardized medical procedure to provide regular outpatient care, examination, health education and follow-up, to reduce and slow down the occurrence of complications in diabetic patients and to enhance the overall quality of care. On the other hands, The NHIA provided transparent information on health care quality, hoping that it would motivate the medical community to improve the quality of medical services offered at every hospital and clinic in 61

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Taiwan. That was also intended to enhance people’s understanding of the NHI system’s quality and treatment options and serve as a reference to help the insured make informed decisions when choosing providers and types of care. It further use as a payment tool. Health care institution could receive extra bonus base on the indicators performance since 2007.

The care rate of DM-P4P program had reached 46% in 2016. Patients who enrolled in the DMP4P program have better compliance for completing follow-up tests such as HbAlc, Funduscopic exam and Microalbumin. Patients with higher HbAlc level between 2005 and 2010 were tracked. Two third of these patients achieved a declination of HbAlc level to normal range after one year.New participants in 2005, after 11 years follow up: HbAlc and LDL test value of the normal proportion of check-ups are growing year by year,. They also have lower incidence rate of dialysis. Patients can get good treatment results if they follow doctor’s advice, receive continuous health education, follow up regularly and change their lifestyle. They can also avoid or delay the occurrence of complications. In 2012, DMP4P program was included in Fee Schedule due to its excellent performance, expanding the number of beneficiaries and improving the quality of care in all aspects.

In July 2013, the NHIA completed the first phase of the patient-centered NHI PharmaCloud System. Through NHI PharmaCloud System, the physicians can inquiry into the latest 3-years prescriptions of DM patients such as medication and examination. We can facilitate patient’s drug safety and reduce duplicate prescriptions.In September 2014, the NHIA completed the “My Health Bank” system. In this system, we also provide hyperlinks of health information. Nowadays, “My Health Bank” has been widely used in health care. Untill September 2016, 1.54 million people had inquired their own medical record. After data visualization, patients can easily inquiry into their medical records and increase their capability to manage their own health.

Institutions’ quality of care is expected to enhance by improving care rate of diabetic patients continuously, tracking and disclosing the outcome of health care quality performance. Another physician can share the medical record through NHI PharmaCloud System to improve patient tracking and management efficiency. Patients can use “My Health Bank” for self-health management. Through the above methods, an integrated and comprehensive diabetic care network will established by cooperation of patient, institution and NHI in the future.

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Abstract DAROC-4

醫學中心到基層醫療健保：糖尿病疾病照護的未來 李伯璋 衛生福利部中央健康保險署

根據國際糖尿病聯合會 (IDF) 於 2017 年更新的全球糖尿病地圖 ( 第八版 )，估計 2045 年全球 糖尿病人口將高達 6.29 億人，依國健署 2013-2015 年調查：18 歲以上國人糖尿病盛行率也高達 11.8%，糖尿病患者已突破 227 萬人。而糖尿病不僅會引發多種嚴重併發症，惡化病患生活品質， 也是近年國人十大死因前五名，同時更造成醫療花費支出的負擔。但其實糖尿病可透過定期追蹤、 積極控制及有效治療，以延緩病情惡化及晚期併發症的發生。因此，糖尿病的預防及治療是我國 重要的醫療課題。 由於論量計酬無法有誘因提升醫療品質，論質計酬 (pay for performance) 則為近年各國提倡之 改革主流，但醫療品質之衡量不易，同疾病之醫療品質測量亦有極大之差異，如何提昇疾病照護 的效果及效率，達到以最符合成本效益的原則，即為台灣推行論質計酬之主要思考方向。疾病之 選擇主要針對費用大、罹病人數多、照護模式有改善空間之疾病為優先。採取論「品質」付費的 支付方式，提供適當誘因。健保醫療給付改善方案 ( 論質計酬方案 )，自 2001 年起每年編列專款 辦理 ( 以 2017 年為例，編列約 17 億元 )，目前辦理項目除糖尿病、氣喘、乳癌、思覺失調症、B 型與 C 型肝炎帶原者、初期慢性腎臟病、早期療育、孕產婦全程照護外，2017 年更增加慢性阻 塞性肺病 (COPD)，總計 9 項論質計酬方案。 中央健康保險署於 2001 年實施「全民健康保險糖尿病醫療給付改善方案」，主要係結合共 同照護及論質計酬的慢性病照護模式，提供糖尿病患者完整的「團隊照護系統」，包括醫師、護 理師、營養師、衛教人員組成共同照護團隊，團隊人員均須定期接受繼續教育訓練。醫療院所須 建立完整、合理、結構化的標準化醫療流程，提供定期的診察、檢驗、衛教及追蹤，降低及延緩 糖尿病患者併發症的發生，提升整體照護品質。另為幫助民眾能確實掌握醫療院所的醫療品質資 訊，做為就醫參考，利用健保給付資料分析，建立偵測醫療院所醫療品質的指標，並透過品質指 標公開，作為參與院所評比依據，進而不斷提升對患者的照護品質，並自 2007 年依品質指標評 核給予品質加成鼓勵。 「全民健康保險糖尿病醫療給付改善方案」照護人數逐年增加，至 2016 年達到整體 糖尿病患者的 46%。每年參與個案的治療遵循率皆高於未參加者，如 HbA1c、眼底檢查及 Microalbumin。 且 經 追 蹤 2005-2010 年 初 診 HbAlc ＞ 9.5% 的 新 收 個 案，1 年 後 有 66% 個 案 的 HbAlc 檢驗值下降至正常範圍，另持續追蹤 2005 年參與方案者自 2006-2015 的年底檢查值 :HbAlc 及 LDL 檢驗檢查值正常比例皆逐年成長，上述患者的洗腎發生率亦低於未參加方案者，顯示參 與「全民健康保險糖尿病醫療給付改善方案」的糖尿病患者若遵循醫囑，並持續接受衛教及定期 追蹤，以及自我生活型態改變，皆能得到良好的治療成效，亦可避免或延緩併發症的發生。2012 年因方案執行成效良好，已導入支付標準，擴大受益人數，全面提升照護品質。 2013 年 7 月健保署建置完成以病人為中心的「健保雲端藥歷系統」，醫師可利用雲端藥歷來 63

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管理追蹤糖尿病患者近三年的用藥及檢驗狀況，減少重複用藥的可能，以增進病人用藥安全。另 於 2014 年 9 月起建置「健康存摺」系統，提供各種健康資訊可供使用者自行點閱查詢。健康存 摺的使用人數自推廣以來，已呈現倍數般的成長，統計至 2016 年 9 月已有 154 萬人使用，糖尿 病患者可透過健康存摺做好自我健康管理追蹤。 未來我們希望持續提升糖尿病患者照護率，同時透過追蹤及公開醫療品質指標，以提升院所 提供的照護品質；另醫師可透過電子病歷的雲端分享，提升病患的追蹤及管理效益，糖尿病患者 能運用健康存摺做好自我健康管理。透過上述方式，讓健保、院所及民眾共同合作，建立更完善 的糖尿病照護網絡。

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Abstract MTP-1

AUTOIMMUNITY AND THYROID CARCINOMA ROSSELLA ELISEI Associate Professor of Endocrinology, University of Pisa

Thyroglobulin (Tg) is a protein produced and secreted only by thyroid cells. Its production is maintained also by tumoral cells in well differentiated thyroid cancer (DTC) such as papillary (PTC) and follicular (FTC) hystotype. Since many years, it has been recognized as the most sensitive and specific marker of residual thyroid tissue and/or persistence/recurrence of the disease in patients affected with DTC and treated with total thyroidectomy (TTx) and post-operative remnant ablation (RRA) with radioiodine (131I).

However, approximately 25-30% of patients with DTC have serum thyroglobulin antibodies (TgAb) which interfere with Tg measurement, causing either false negative (by immunometric assays) or false positive results (by radioimmunological assays). TgAb are the expression of an associated lymphocytic thyroiditis (LT) or the expression of an immune reaction to DTC. In these cases, serum Tg loses its function as tumor marker, but the change of the serum TgAb levels over the time can be used as a “Tg surrogate” since it has been demonstrated that in cured DTC patients, the TgAb levels decline to reach the negativization. At the same time, the persistence of stable levels of TgAb for a long period of time or the increase of TgAb levels after TTx plus/minus RRA represent an alert about the possibility of persistence or recurrence of DTC. Currently, this concept is so well established that the new international referral guidelines for the management of DTC include the TgAb evaluation after initial treatment as essential to assess the ongoing risk stratification.

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MTP-2

CLINICAL MANAGEMENT OF TYPE 2 DIABETES WITH CHRONIC KIDNEY DISEASE IN JAPAN: CURRENT SITUATION AND STRATEGY ABE MASANORI Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan

Type 2 diabetes mellitus is among the leading causes of end-stage kidney disease (ESKD) worldwide. However, in Japan, the percentage of patients who had initiated dialysis because of diabetic nephropathy has not increased in recent years. A probable reason for this is that angiotensin II receptor blockers, ARBs, came into general use in Japan from 2000 onwards, and we can also use DPP-4 inhibitors. Furthermore, the sodium-glucose cotransporter 2 (SGLT2) inhibitors provided kidney protection. Therefore, we can easily treat diabetes even in patients with chronic kidney disease (CKD). But, in Japan, there’s a prominent primary cause of CKD. It is hypertensive nephrosclerosis.

Nephrosclerosis is caused by long-term hypertension. Japan has the highest aging population ratio, and consequently, nephrosclerosis continues to increase in Japan. So, to prevent ESKD, diabetic nephropathy, which is the most common primary disease, and ever increasing nephrosclerosis are the important diseases to target for Japan.

Here, we will describe the cardio-renal connection, and show the different trajectories between diabetic nephropathy and nephrosclerosis. Finally, we will describe the kidney protection by SGLT-2 inhibitors for diabetic kidney disease.

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Abstract SE1-1

GRAVES’ OPHTHALMOPATHY-CLINICAL EXPERIENCES IN KOREA JEE HEE YOON Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea

Graves’ disease is the most common cause of thyrotoxicosis in Korea (82.7%) and up to 50% of patients with Graves’ disease develop Graves’s ophthalmopathy (GO). GO is related to the loss of immune tolerance to the thyrotropic receptor (TSHR) andorbital fibroblasts, the target cell of GO, increase connective tissue edema in the bony orbits by secreting pro-inflammatory cytokines andhydrophilic hyaluronanin early phase and lead to orbital adipose tissue expansion by differentiating to mature adipocyte in late phase. The pathogenesis of GO is becoming more clear, but some part of that is still understood incompletely. For the optimal management of GO, reducing risk factors and proper approach depending on clinical activity of GO (active inflammatory phase and chronic static phase) are necessary. The cessation of smoking and sustenance of a euthyroid state is helpful for the decreasing risk factors. For reducing inflammation in patients with active GO, systemic steroid only or with radiotherapy generally, but clinical outcome is sometimes insufficient. Other approaches for targeting immune mechanism of active GO were studied and good result of teprotumumab targeting for insulin-like growth factor-I (IGF-I) is reported recently. Surgery is indicated for emergent optic compression and management of chronic phase.

In this session, I hope to share our cases of GO and clinical data in Korea.

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SE1-2

MEDICAL TREATMENT OF GRAVES’ ORBITOPATHY SHYANG-RONG SHIH Department of Internal Medicine, National Taiwan University School of Medicine Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital

Graves’ orbitopathy (GO) occurs in up to 50% of patients with Graves’ disease. Although GO is usually self-limiting, many patients cannot tolerate the sequelae. Proptosis, diplopia, corneal erosion, and visual loss may persist and handicap throughout life. After plateaus of active disease, a quiescent burnt out phase ensues. But reactivation of inflammation occurs in about 5%-10% of patients over their lifetime. Medication or surgery is offered in order to prevent or treat symptoms, corneal exposure, globe protruding, or optic neuropathy. Treatment plan is made according to the severity and activity of GO. In order to treat GO, euthyroidism should be restored, and smoking should be quitted. All patients should be treated with nonpreserved artificial tears with osmoprotective properties. Selenium supplementation and oral pentoxifylline may offer some improvement in mild GO. In active and moderate to severe TED, high-dose intravenous glucocorticoids (GCs) therapy is recommended.

However, adverse effects such as hypertension, hyperglycemia, hypokalemia, infections, peptic ulcer, osteoporosis, hepatitis, and abnormal behavior (including mood alteration, hyperactivity, psychosis, disorientation, sleep disturbances) may occur. Thirty-one percent of the patient would suffer from disease reactivation. If high dose intravenous GCs is not effective, second line of treatment include second course of high-dose intravenous GCs, oral GCs with orbital radiotherapy, oral GCs with cyclosporine, and Rituximab. Orbital radiotherapy may improve diplopia, but may induce transient exacerbation of ocular symptoms which can be controlled by oral GCs. But some studies suggest that radiotherapy has no significant effect compared with natural course of GO. Radiotherapy should be avoided in patients with diabetes or vasculitis, as the radiation may exacerbate retinopathy.

Combination therapy with cyclosporine and oral GCs is another choice for partial responder of high dose intravenous GCs. About 60% of the patients have response. Adverse events of cyclosporine are dose-dependent renal and liver toxicities, and gingival hyperplasia. Rituximab has a direct-B-celldepleting action and can modulated B-cell function. Some study showed that rituximab has 100% effect on GO and disease activity never recurs, but other study failed to demonstrate an improved outcome compared with placebo. Infusion-related reactions are the most frequent side effect, and transient and significant periorbital edema and inflammation may occur. Rehabilitative surgery such as orbital decompression, squint surgery, and lid surgery may be offered after active inflammation subsided.

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THE STRATEGY FOR THE MANAGEMENT OF GRAVES’ OPHTHALMOPATHY YI-HSUAN WEI Department Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, ROC

Graves’ ophthalmopathy (GO) is the most common extra-thyroid manifestation of Graves’ disease. The ocular manifestations represent orbital inflammation, tissue expansion, and fibrosis that often lead to substantial morbidity. The clinical signs of GO may comprise any of the following: conjunctival chemosis, periorbital soft tissue swelling, proptosis, eyelid retraction, restriction of eye movement, and decrease of vision due to exposure keratopathy or compressive optic neuropathy. The exact pathogenesis of GO has yet to be understood, and the disease remains a therapeutic challenge.

Treatment strategies vary depending on disease severity and activity.

In this talk, we will introduce the clinical course of GO as well as the treatment for different stages of disease. We will focus on the surgical management of GO, including orbital decompression, strabismus correction, and eyelid repositioning. Moreover, how to recognize the problematic GO patient is very important to prevent them from irreversible visual impairment. Some complicated or intractable cases will be discussed in this talk.

Endocrinologists and ophthalmologists offer distinct contributions to the care of patients with GO. We believe that the best outcomes come from good coordination between the two specialists.

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th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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CONTRAST-ENHANCED ULTRASOUND (CEUS) OF THE THYROID GLAND YI-HONG CHOU1,2, YUNG-HUI LIN2 1

Yuanpei University of Medical Technology, Hsinchu, Taiwan; 2Department of Radiology, Taipei Veterans General Hospital and School of Medicine, National Yang Ming University, Taipei, Taiwan

High resolution US (US) has been widely used in the diagnosis of small part disorders.

Conventional US has been reported to be associated with a sensitivity of 71.32%, a specificity of 77.04%, a positive predictive value of 69.78%, a negative predictive value of 78.33%, and an accuracy of 74.60% in the diagnosis of thyroid malignancy. The typical US appearances of malignancy include hypoechogenicity, poorly defined boundary/irregular margin, and microcalcifications. However, not all malignancies show typical US features. Contrast-enhanced US (CEUS) may be helpful in some instances.

A uniform high contrast enhancement on CEUS is suggestive of a benign thyroid nodule, especially in favor of an adenomatous nodule. A small hypoechoic lesion with a regular boundary on US and hypo-enhancement (without significant marginal enhancement) on CEUS is suggestive of a papillary carcinoma. A hypoechoic lesion with a regular boundary on US and apparent marginal enhancement on CEUS is more likely to be an adenomatous thyroid nodule with eosinophilic change or hemorrhage. The time-intensity curve (TIC) obtained at CEUS can be also used. As compared with normal thyroid tissue, a malignant thyroid nodules exhibit low peak intensity.

Representative features for thyroid adenomas and nodular goiters on US are either no wash-out or wash-out with persistent edge enhancement in late phase, while thyroid carcinomas show a complete wash-out in late phase. The sensitivity, specificity, positive and negative predictive value of 81%, 92%, 97% and 63%, respectively, have been reported for the differentiation of benignity and malignancy.

Dynamic evaluation of microcirculation using CEUS may provide a more reliable preoperative discrimination between thyroid adenomas and thyroid carcinomas. (Clinical Hemorheology and Microcirculation, 2015;61:13-22). However, a prospective study is necessary for further confirmation on the usefulness of CEUS in the differentiation of benign and malignant thyroid nodules.

To date, US-guided fine needle aspiration cytology and core-needle biopsy are still the most important preoperative diagnostic tools. The role of CEUS in the evaluation of diffuse thyroid disorders is not yet defined. CEUS of the thyroid gland may be of help in the evaluation of minimally invasive therapeutic procedure (e.g., RFA) of thyroid nodules.

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MOLECULAR TESTING FOR THYROID NODULES RUE-TSUAN LIU Tsuan-Huey Clinic

Thyroid nodules are common in adults with a prevalence of approximately 70%. Fine needle aspiration (FNA) with cytologic examinationremains the diagnostic test of choice to distinguish benign from malignant thyroid nodules. However, it fails to discriminate as benign or malignant in up to onethird of cases.To reduce the burden of repeat diagnostic testing and unnecessary surgery, there has been extensive investigation into molecular markers that can be detected on FNA specimens to more accurately stratify a patient’s risk of malignancy. Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer. In this talkI will discuss the limitation of current cytopathologic evaluation, the development of thyroid molecular testing, and the strengths and limitations of commercially available tests, taking into the consideration of my previous work on the molecular genetics of thyroid nodules in Taiwan.

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CURRENT CONCEPT FOR THYROID RADIOFREQUENCY ABLATION WEI-CHE LIN Department Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital

Ultrasound-guided RFA has shown good results for benign thyroid nodules, including autonomously functioning thyroid nodules. For benign thyroid nodules, RFA effectively ameliorates symptoms and cosmetic problems by reducing the thyroid nodule volume. Recent case series also suggest ultrasound-guided RFA as an alternative treatment for recurrent thyroid carcinoma in patients who are at a high risk of complications from surgery or who refuse to undergo repeated surgeries.

According to a recent meta-analysis of ultrasound-guided RFA treatment for locally recurrent thyroid cancer, the therapeutic success is very high with a significant serum thyroglobulin reduction.

The revised American Thyroid Association guideline suggests ultrasound-guided RFA as a useful alternative to surgical resection of metastatic thyroid cancer. Although RFA has been shown to be an excellent treatment modality for benign thyroid nodules and recurrent thyroid cancers, several RFAassociated complications have been reported, including voice change, skin burns, hematoma formation, and hypothyroidism. In this talk, we will brief introduce the indication for thyroid RFA, some technique for the procedure and the possible complication associated with RFA. In the end, we will also like to share the biggest result of Taiwan in the treatment of benign thyroid goiter in Kaohsiung Chang Gung Memorial Hospital.

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Abstract SE2-4

NEW APPLICATION OF GENETIC TESTING IN CLINICAL DIAGNOSIS YI-NING SU Dianthus Maternal Fetal Medicine Clinic, Taipei, Taiwan; Sofiva Genomics Co., Ltd., Taipei, Taiwan.

With the rapidly changing technological platforms in the genetic testing and clinical diagnostics fields, the next-generation sequencing (NGS) has been the major player in non-invasive prenatal screening (NIPS), and liquid biopsy. NIPS and liquid biopsy share the similar mechanism by testing the cell-free fetal DNA (cffDNA) and circulating tumor DNA (ctDNA) in the bloodstream, respectively.

The major advantage of NIPS and liquid biopsy is non-invasive procedure. In NIPS, the fetus shed fetal DNA into mother’s bloodstream as well as in liquid biopsy, the tumor cells release tumor DNA into patient’s bloodstream, and the genetic testing can thus detect by drawing blood from the mother or patient. The major difference is NIPS applies in the pregnancy to detect fetal chromosomal aneuploidy while liquid biopsy is for cancer to identify tumor DNA mutations. Unlike the invasive chorionic villus sampling (CVS) or amniocentesis that needs insert a needle through the cervix or abdomen, and biopsy needs to remove a piece of tissue by a surgeon.

NIPS used NGS-whole exome sequencing based and covers the whole fetal genome, i.e 23 pairs of chromosomes. Moreover, NIPS especially focus on the most common chromosomal disorders, including trisomy 13 (Patau Syndrome), trisomy 18 (Edwards Syndrome), and trisomy 21 (Down Syndrome). Furthermore, NIPS now can detect microdeletion syndromes, and also apply to testing for single gene disorders, for example, skeletal dysplasia genetic mutations.

Liquid biopsy can be used to early cancer detection, tumor genotyping, identification of drug resistance markers and monitor the tumor situation during the treatment. Liquid biopsy uses a sensitive NGS-based targeted assay, and detects four relevant mutation classes, including single nucleotide variations (SNVs), insertions/deletions, copy number variations (CNV) and structural rearrangements.

It allows detecting tumor-specific alterations and monitoring tumor heterogeneity. Moreover, by noninvasive blood-based monitoring mutation dynamics during therapy enables to have better temporal sampling of tumor evolution. Besides, it can monitor treatment response, disease progression and reoccurrence.

NIPS and liquid biopsy are the most advanced non-invasive genetic testing, and available in routine clinical testing. Both NIPS and liquid biopsy hold great potential in the future for further applications.

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NATIONAL PA REGISTRY-BASED EVIDENCE FORCLINICAL PRACTICE OF PRIMARY ALDOSTERONISMIN JAPAN MITSUHIDE NARUSE1, JPAS STUDY GROUP1 1

Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

Primary aldosteronism (PA) is a representative cause of endocrine hypertension characterized by an excess production of aldosterone, hypertension, and various cardiovascular complications.

Although clinical practice guidelines have been published, details of each diagnostic stephave not been standardized and heterogeneous clinical practice between institutes and countries remain to be resolved. The aim of the study was to produce evidence to improve clinical practiceof PA in Japan through National registry. Methods: We established the National PA registry by multicenter collaboration of 28 referral centers (Japan PA Study: JPAS). 2800 patients who were diagnosed as PA by positive case detection and at least one positive result in confirmatory testing and underwent AVS between 2006 and 2016 were registered.Results:1) Prevalence of cardiovascular diseases, especially stroke, was significantly higher in PA patients than essential hypertension. Hypokalemia, unilateral subtype and/or PAC larger than 125pg/ml were at greater risk of cardiovascular diseases and had greater need for PA-specific treatment, 2) Since clinical manifestation of PA in the elderly waslike that in younger patients, diagnostic process of PA should follow the same clinical practice guideline even in the elderly, 3) Saline infusion test as a confirmatory testing was useful also for subtype diagnosis,4) More than 90% of PA patients with normokalemia and bilateral disease on CThad bilateral subtype on AVS and AVS is recommended less weakly, while thoseyounger than 35 years with marked PA (hypokalemia and unilateral disease on adrenal CT) could be spared, 5) While biochemical benefit after ADX was achieved solely with Lateralization Index larger than 4 of AVS, clinical benefit was affected not only by LI but also clinical findings such as age, BMI, and blood pressure, 6) Prevalence of cortisol co-secretion was significantly increased in PA with adrenal tumor larger than 2 cm in diameter, suggestingan importance of dexamethasone suppression test. LI larger than 4 was applicable for PA subtype diagnosis even in patients with PA with subclinical cortisol co-secretion, but not in those with overt Cushing syndrome, 7) Although effects of ADX and medical therapy in unilateral PA were comparable in the reno- and cardiovascular events during the 1 year follow up after treatment, ADX provided superior results in correcting hypertension and hypokalemia.Conclusions: Various evidence for elaboration and simplification of clinical practiceof PA was created by excluding institutional bias through National PA registry in Japan. PA registry could serve as a unique infrastructure for future research and development of new diagnostic methods and treatment of PA.(This research was supported by AMED, Japan Agency for Medical Research and development, for the Practical Research Project for Rare/Intractable Diseaseunder Grant Number JP17ek0109122).

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ADRENAL VENOUS SAMPLING IN NTUH CHIN-CHEN CHANG Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

Hypokalemia and refractory hypertension usually lead to an increased likelihood of primary aldosteronism (PA), which is the most common cause of secondary hypertension. The main causes of PA are aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH). Unilateral laparoscopic adrenalectomy is usually the treatment of choice for patients with APA, whereas patients with IAH are normally treated with medicines. Adrenal venous sampling (AVS) was introduced in late 1960s as a test to distinguish unilateral from bilateral primary aldosteronism. AVS is held to be the “gold standard” diagnostic procedure for assessing lateralization of aldosterone secretion and thereby identifying the surgically curable forms of primary aldosteronism.

The successful cannulation of both adrenal veins continues to be challenging clinical issues.

Adequate adrenal sampling is based on higher cortisol concentration compared with peripheral sampling. We introduced Dyna-CT into the AVS procedure since 2012 and on-site quick cortisol assay (QCA) since 2015. The successful rate had been improved to 97% in non-stimulated AVS. The development of AVS relies on cooperation with teammates in Taiwan Primary Aldosteronism Investigation (TAIPAI) study group. We have gradually improved the performance on AVS that can be dedicated to the academic research.

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CASE DETECTION AND DIAGNOSIS OF PRIMARY ALDOSTERONISM -THE CONSENSUS OF TAIWAN SOCIETY OF ALDOSTERONISM YA HUI HU Division of Endocrine and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Taiwan, ROC

臨床上有懷疑 PA 的病人，需要進行 ARR (aldosterone/PRA) 篩檢，到底哪些人應該被篩檢？ 日本內分泌學會發表的原發性醛固酮症指引中，建議所有高血壓的病人都應該篩檢，在台灣臨床 工作中，對任何疑似 PA 的病人，都可以進行篩檢，例如低血鉀或病患使用 ACEI/ARB 其鉀離子 不如預期那麼高、阻抗性高血壓、電腦斷層意外發現腎上腺腫瘤、太過年輕發病高血壓、病患或 是家族有年輕中風病史等等。我們針對疑似 PA 的病人進行 ARR 篩檢，如果篩檢陽性則需要進一 步做確定診斷，確定診斷的檢測方法很多，在台灣比較常被使用的是生理食鹽水灌注試驗 (saline infusion test, SIT)、captopril 試驗 (captopril challenge test, CCT) 或 ARB 抑制試驗。需要注意的是， 進行 ARR 篩檢時，應盡可能地先矯正低血鉀，倘若 ARR 篩檢正處於低血鉀之際，篩檢可能呈 現假陰性，但如果這時候篩檢呈現陽性，且血漿腎素活性 (plasma renin activity) 低到無法偵測、 血漿醛固酮濃度高 (plasma aldosterone concentration, PAC ＞ 20 ng/dL)，那麼此患者可以不需要再 76

Abstract

進行確診試驗。確診試驗陽性的病人需進行亞型分析，先執行腎上腺電腦斷層影像檢查，具有明 顯腫瘤的患者，如果年齡小於 35 歲並且具足原發性醛固酮瘤特質 ( 血鉀低，ARR 很高，電腦斷 層呈現均質富含脂肪的腎上腺腫瘤 ) 可以直接進入手術，但是如果沒有把握或年齡大於等於 35 歲，最好先做功能性的定位，確定醛固酮大量分泌是來自於哪一側，如果是單側功能性的醛固酮 瘤 (APA)，建議進行後腹腔內視鏡腎上腺摘除手術，如果是雙側增生，建議病人長期服用礦物性 皮質素受體拮抗劑 (mineralocorticoid receptor antagonist, MR 拮抗劑 ) 治療。目前台灣有兩項檢查可 以用來執行功能性定位，用以區分醛固酮瘤 (APA) 與雙側增生，第一種是非侵襲性的核子醫學造 影 (NP-59 SPECT/CT)，第二種是腎上腺靜脈採血檢測 (adrenal venous sampling, AVS)，這是目前全 球公認區分亞型的黃金標準檢測，是一項侵入性的檢查，需要把導管置入兩側腎上腺靜脈採血， 此項檢查需要訓練精良的醫師執行，因為右側的腎上腺靜脈採血非常困難，NP-59 SPECT/CT 或 AVS 執行後，如果檢查結果不夠明確，可以兩項都做。當電腦斷層沒有明顯腫瘤，倘若臨床醫師 仍懷疑患者可能有醛固酮瘤 ( 低血鉀、血壓特高、ARR 特高等 )，可以執行 AVS 檢測，以偵測小 的醛固酮瘤。對於電腦斷層沒有明顯腫瘤且臨床上沒有高度懷疑醛固酮瘤的患者，建議長期服用 MR 拮抗劑治療。

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從偶發性的甲狀腺結節談起 陳涵栩 臺北榮民總醫院內分泌新陳代謝科

甲狀腺結節是一種常見的臨床問題。流行病學的研究顯示：甲狀腺結節的盛行率在婦女約 5% 而在男性約 1%。然而，高解像力的超音波可以在 40-60% 隨機選擇的個人發現甲狀腺結節。 甲狀腺結節的臨床重要性是需要排除甲狀腺癌。 所有已知或疑似甲狀腺結節的患者應該以血清甲促素 (TSH) 的測定以及甲狀腺超音波 做為初步的檢查。如果血清 TSH 低於正常，應考慮進行放射性同位素甲狀腺掃描。稍高的 血清 TSH 濃度與甲狀腺結節中惡性腫瘤的風險增加相關，需要進行細針穿刺細胞學檢查。 另外血清 TSH 如果正常或升高，放射性同位素掃描不應作為初始的影像評估，以免將囊腫 (Cyst) 誤判成冷結節。應在所有已知或疑似甲狀腺結節的患者中進行甲狀腺超音波檢查， 並且應該包含頸部淋巴結的檢查。 細針穿刺細胞學檢查是在評估甲狀腺結節時重要的臨床檢查，而根據甲狀腺超音波檢查的 甲狀腺結節超音波圖譜，對於甲狀腺結節是否需要進行診斷性的細針穿刺細胞學檢查，可以提 供很好的建議。根據甲狀腺超音波檢查的甲狀腺結節的超音波圖，可以先將甲狀腺結節分成高 度懷疑、中度懷疑、低度懷疑、以及非常低度懷疑是惡性的超音波圖譜，然後根據甲狀腺結節 的超音波圖的懷疑等級訂出需要穿刺的最小直徑。 FDG-PET 掃描可以作為甲狀腺結節是否需要接受 細針穿刺細胞學檢查的參考。 如果 18FDG-PET 是局部性 (focal) 的攝取增加，甲狀腺癌風險的機會也增加，所以建議對於 > 1cm 的結節進行細針穿刺細胞學檢查。瀰漫性 (diffuse) 的 18FDG-PET 攝取，連同慢性淋巴 細胞性甲狀腺炎的甲狀腺超音波和臨床證據，則不需要進一步影像學檢查或進行細針穿刺 細胞學檢查。

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Abstract SE4-2

THE ROLE OF FINE NEEDLE ASPIRATION, CYTOLOGY INTERPRETATION, AND MOLECULAR TESTING FOR THYROID NODULES SHU-FU LIN Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Thyroid nodules are a common clinical disease, and differentiated thyroid cancer is becoming increasingly prevalent. Diagnostic thyroid ultrasound (US) should be performed in all patients with a suspected thyroid nodule. Fine needle aspiration (FNA) is a simpleprocedurewithhighaccuracy for evaluating thyroid nodules. US-guided FNA is preferredfor nodules with a higher likelihood of a nondiagnostic cytology or sampling error. The FNA may be performed using palpation if the diagnostic US confirms the presence of a predominantlysolid nodule corresponding to what is palpated.

According to American Thyroid Association guideline 2015,thyroid nodule FNA cytology should be reported using diagnostic groups outlined in the Bethesda System for Reporting Thyroid Cytopathology. This system consistsof six diagnostic categories, including (i) nondiagnostic/ unsatisfactory; (ii) benign; (iii) atypia of undetermined significance/follicular lesion of undetermined significance; (iv) follicular neoplasm/suspicious for follicular neoplasm, a category that also encompasses the diagnosisof Hu¨rthle cell neoplasm/suspicious for Hu¨rthle cellneoplasm; (v) suspicious for malignancy, and (vi)malignant, and provides an estimation of cancer riskwithin each category.

Molecular markers are frequently used for diagnostic,prognostic or predictive purposes. The proposeduse of molecular markers in indeterminate thyroid FNA specimens is diagnostic and with the implication of a companion use to informdecision-making on primary surgical treatment.A number of molecular approaches have been studied in the clinical setting of indeterminate FNA cytologic interpretation.

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細胞學檢查後的部份對策 施翔蓉 臺大醫學院內科／臺大醫院代謝內分泌科

當細針穿刺細胞學檢查結果為不確定良惡性 (indeterminate: AUS/FLUS, FN, SUSP) 時，並不建 議常規使用正子掃描檢查去判別結節的良惡性。 關於手術方式，當細針穿刺細胞學檢查結果為不確定良惡性時，如果結節只有一顆，建議一 開始採用甲狀腺單側切除術。但這也不是一定的，可依照臨床狀況、超音波影像、病人需求、分 子生物學檢查等等來調整。在有惡性機率增加的狀況，且若之後甲狀腺單側切除病理檢查結果為 惡性時將建議雙側甲狀腺全切除的話，在一開始細針穿刺細胞學檢查結果為不確定良惡性時，會 建議甲狀腺全切除比較合適。若之後甲狀腺單側切除後病理檢查結果發現為惡性時將建議雙側甲 狀腺全切除的話，當病人有雙側結節、或有明顯的其他疾病、或是病人希望接受雙側甲狀腺切除 術以避免之後還有需要再切除另一側甲狀腺的狀況，可考慮在一開始細針穿刺細胞學檢查結果為 不確定良惡性時，接受甲狀腺全切除術。 關於細針穿刺細胞學檢查結果為良性的甲狀腺結節長期追蹤計畫，建議應依超音波影像特徵 而異。若結節有高度懷疑惡性的超音波影像特徵，應在一年內接受超音波和超音波導引細針穿刺 細胞學檢查。若結節有低到中度懷疑惡性的超音波影像特徵，建議應每 1 到 2 年接受一次超音波 檢查。若超音波影像顯示結節有明顯增大或有產生新的疑似惡性的超音波影像特徵，則應接受細 針穿刺細胞學檢查；或是繼續以超音波觀察追蹤，若結節持續增大，則安排細針穿刺細胞學檢查。 若結節具有非常低度懷疑惡性的超音波影像特徵，追蹤超音波觀察結節有無變大以決定是否需要 安排細針穿刺細胞學檢查的效果很有限。 若結節沒有達到細針穿刺細胞學檢查的標準而沒有接受穿刺檢查，則追蹤計畫應也是依超音 波影像特徵而異。

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Abstract SE4-4

懷孕期間發現的結節的處置 蘇登煌 遠東聯合診所醫護部

懷孕婦女的結節的盛行率大約 3 到 21% 間，隨著其懷孕的年紀次而增加，大多數在懷孕期 間發現的結節為原先在懷孕前已存在的結節，而懷孕會跟原先已存在的結節的大小增加有關，並 跟部分的新結節的生成有關。目前並無研究顯示懷孕期間發現的結節的惡性可能性並不比沒有懷 孕期間發現的結節為高。懷孕期間發現的惡性結節很少見。過去研究中顯示第二妊娠期進行行甲 狀腺手術，並沒有任何母親或新生兒的後遺症。如果要在懷孕期間進行手術，為了最小化流產的 風險，手術應在妊娠 24 週前的第二妊娠期內進行，且應由熟練的外科醫師執行，以減少第一妊 娠期進行手術所可能導致胎兒的器官病變及自動流產和第三妊娠期進行手術所可能導致的早產。 對於分化型甲狀腺癌的手術時間，延後手術時間到產後對預後沒有影響，而懷孕對於分化型甲狀 腺癌的預後的影響並沒有定論。細針穿刺在懷孕期間仍是一個安全的診斷工具，可在任一妊娠期 內進行。標準的細胞診斷標準可適用於懷孕期間發現的結節。 對於甲狀腺功能正常或低能的懷孕婦女，如遇到臨床上有意義的結節，細針穿刺可於任一 妊娠期內執行或延到懷孕結束後執行細針穿刺檢查。但對於超音波追踨中快速長大或有症狀的 結節，細針穿刺應該執行。對於細胞學檢查為良性的懷孕婦女，懷孕期間並不需要特別的監測 策略，其處置同未懷孕的婦女，且不建議使用甲狀腺素壓抑治療。如結節的細胞學結果為不確 定時，若無嚴重的局部症狀或令人擔心的現象 ( 如妊娠 24-26 週前急速長大或超音波下有疑似淋 巴結轉移 )，手術應延到產後進行，相反地，若臨床上呈現侵略性的行為，則應考慮手術。分子 標誌分析的角色在懷孕中為不確定。如結節的細胞學結果為惡性時，若於早期懷孕時，經由細胞 學檢查診斷為甲狀腺癌之婦女應該用超音波監測。假如它在妊娠 24-26 週前急速長大 ( 即結節的 長寬高其中有兩個象限增大 20% 以上且至少增大 2 mm 以上，或是結節的體積增大 50% 以上 ) 或 超音波下有疑似淋巴結轉移的現象，手術應在第二妊娠期間進行。反之，若此腫瘤在妊娠中期都 很穩定，手術應延至生產後。但如細胞學檢查診斷為髓質癌或未分化癌，則應進行手術。如於第 三妊娠期間診斷為甲狀腺癌之婦女，手術應延至生產後。如遇到懷孕期間發現甲狀腺結節的婦女， 可依上述建議及超音波變化擬定合適的方針。

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SE4-5

POST-OPERATIVE RISK ASSESSMENT AND RADIOIODINE THERAPY OF DIFFERENTIATED THYROID CANCER YEN-HSIANG CHANG Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, ROC

In 2015, the American Thyroid Association (ATA) renewed the guidelines regarding the management of differentiated thyroid carcinoma (DTC) based on the results of studies published since 2009. According to the new evidences, the treatment of DTC has continued to modify and evolve.

Post-surgical radioactive iodine (RAI) ablation is almost routinely performed, however, recent studies showed that ablation is not beneficial for survival in low-risk patients. Recombinant human thyroid-stimulating hormone (rhTSH) has been recommended as the first line mode of TSH stimulation except for high risk patients or those with recurrent/metastatic disease. Although low-dose (30mCi) ablation showed similar ablation rate to high-dose ablation, long-term outcome has not yet been established.

According to the follow-up of DTC patients, no single factor is capable of completely predicting the long-term outcomes. The concepts of “dynamic risk assessment” have important implications on DTC management during follow-up.

Recently, policy for treating DTCs has changed in many aspects and tends to be more “personalized”. We have to continue to capture the new information with time to present the best treatments for DTC patients.

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Abstract SE5-1

UP-TO-DATE OF CLINICAL PRACTICE OF PHEOCHROMOCYTOMA/ PARAGANGLIOMA MITSUHIDE NARUSE1, MIKA TSUIKI1,2, HIRONOBU UMAKOSHI1,2, TETSUYA TAGAMI1,2, AKIYO TANABE3, PHEO-J STUDY GROUP1, ACPA-JSTUDY GROUP3 1

Clinical Research Institute of Endocrinology and Metabolism, 2Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto,3Department of Diabetes and Endocrinology, National Center for Global Health and Medicine, Tokyo, Japan

A tumor of chromaffin cells of the adrenal medulla is termed as pheochromocytoma and that of the extra-adrenal paraganglion system is termed as paraganglioma with a general term of pheochromocytoma/paraganglioma(PPGL).While bilateral, extra-adrenal, multiple, or malignant disease is about 10% of PPGL, germline mutation has been demonstrated in about 30%.PPGL has 2 unique clinical aspects, hypersecretion of catecholamine (CA) and malignant potential, requiring comprehensive clinical practice among the related departments. Diagnosis of treatment of PPGL follows the Clinical Practice Guidelines of the task force group for Pheochromocytoma by Ministry of Health, Labor and Welfare in Japan (2012) andClinical Practice Guideline for Pheochromocytoma and Paraganglioma of Endocrine Society (2014).Major chances of making diagnosis are 1) various symptom termed ‘Spell’, 2) hypertension (paroxysmal, crisis, treatment-resistant, complication of diabetes mellitus) and 3) adrenal incidentaloma, which can be designated as ‘PPGL-high risk’ group.

Clinical practice of PPGL consists of 3 major steps: functional diagnosis of excess CA excretion, imaging diagnosis of tumor localization, and choice of treatment.Functional diagnosis includes measurement of plasma CA levels, fractionated metanephrines in spot urine, and 24 hrs urinary CA excretion. Determination of plasma and urine CA during paroxysmal hypertension is also useful.

Plasma free-metanephrines accounting for 10% of the total has been recommended as the most sensitive and specific confirmatory test. Diagnostic imaging includes adrenal CT scan and MRI. Since 90% of PPGL is pheochromocytoma, the primary tumor is readily recognized in the adrenal.

Combination of CT, MRI, and 123I-MIBG scintigraphy is indicated if the primary tumor is not found.18F-FDG-PET is usefulin detecting metastatic lesions of malignant PPGL.Laparoscopic tumor resection after enough amount and period of treatment with alphablocker doxazocin is the principle choice of treatment. The lecture will focus on current topicsincluding the new WHO classification, asymptomatic PPGL, genetic testing, pathological grading of malignancy, CA synthase inhibitor metyrosine, and new radionucleotide therapy in addition to the general aspects of clinical practice of PPGL.(Funding: Supported by the Health Labor Sciences Research Grant for the Research on Measures for Intractable Diseases from Ministry of Health Labor and Welfare in Japan, the National Center for Global Health and Medicine, Japan,27-1402) 83

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SE5-2

GENETICS AND DIAGNOSIS OF PHEOCHROMOCYTOMA/ PARAGANGLIOMA PEI-LUNG CHEN Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Departments of Medical Genetics and Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan, ROC

Pheochromocytoma (PCC) and paraganglioma (PGL) are catecholamine-secreting tumors of neural crest origin, derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are very important diseases drawing high attention. Clinically, although often benign tumors, they are associated with high morbidity and mortality because of mass effect and high blood circulating catecholamines. Roughly one quarter of PCC/PGL are malignant. Furthermore, high recurrence rate in family members, but lack of a reliable prediction which members to be affected, makes the diseases daunting. Scientifically, PCC/PGL are tumors related to the hypoxia pathway, and many known causative genes are also key players of neoplasia syndromes, such as multiple endocrine neoplasia, neurofibromatosis, etc. Therefore, basic research on PCC/PGL often shed light on the mechanism of fundamental pathways. PCC/PGL are actually not rare, and the prevalence figures approximate 0.2% in autopsy series. The mean age at diagnosis is about 40 years, with slight female preponderance.

Clinical manifestations can vary widely, depending on the predominant type of catecholamine secreted (epinephrine, norepinephrine, dopamine), the presence of co-secreted neuropeptides and whether secretion is sustained or episodic. A characteristic presentation is intermittent paroxysms of symptoms and signs related to episodic catecholamine release, including hypertension, headache, anxiety, sweats, pallor, flushing or palpitation. Traditional diagnosis relies on clinical presentations, biochemistry data (VMA, catecholamines, metanephrine, normetanephrine, etc.) and image examinations. However, variable and non-specific manifestations make early diagnosis a real challenge.

There are at least 15 well-documented genes (NF1, RET, VHL, SDHD, SDHC, SDHB, SDHAF2, SDHA, TMEM127, MAX, FH, KIF1B, EGLN1, RASH1 and EPAS1) that can cause PCC/PGL with an autosomal dominant transmission. Other additional genes were recently reported to cause PCC/PGL through somatic mutation (ARNT, ATRX, BRAF, CSDE1, FGFR1, IDH1, SETD2 and TP53) or gene fusion (BRAF, MAML3 and NGFR). NGS disease panel is a powerful tool for genetic diagnosis. Better databases are needed to clarify the pathogenicity of certain identified variants. Progress in genetics/ genomics can provide better genetic diagnosis and counseling, as well as guide the treatment strategy.

Furthermore, identification of novel PCC/PGL-causing genes has the potential to shed light on the pathophysiology of PCC/PGL, which could potentially lead to new therapeutic breakthrough.

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Abstract SE5-3 SURGICAL TREATMENT OF PHEOCHROMOCYTOMA KUO-HOW HUANG Department Radiation Urology, National Taiwan University Hospital, Taipei, Taiwan, ROC

Pheochromocytomas are relatively uncommon tumors among adrenal tumors. Patients with pheochromocytomas are potentially curable by surgical treatment; however, pheochromocytomas present a substantial risk of morbidity and mortality during or after surgical procedures. In recent decades, most pheochromocytoma could be surgically treated by minimally invasive methods. In this speech, I will talk about pre-operative preparation, principles of surgery, anesthetic management, intra-operative considerations, surgical outcomes and post-operative follow-up and share with the experiences on surgical outcomes of pheochromocytoma in our institute.

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SE6-1 CURRENT CHALLENGES IN THE TREATMENT OF PATIENTS WITH HYPERLIPIDEMIA WEI-SHIUNG YANG Department Internal Medicine, National Taiwan University Hospital Taipei,, Taiwan,

Hyperlipidemia is a major modifiable risk factor in the pathogenesis of atherosclerosis. In the past decades, we have witnessed a huge progress in the management of hypercholesterolemia. With the use of statins and ezetimibe, we are able to reduce blood LDL-C and consequently the CV risk in patients with hyperlipidemia. Recent introduction of PCSK9 inhibitors further moves this field into a new era in which we can even bring down the LDL-c to a level which we could hardly imagine before.

But the questions remain, first whether there is still residual CV risk after this and how we can manage it; second how low the bottom of LDL-C lowering will be. Should we continue to explore the bottom of LDL-C lowering and hope that this may reduce the CV risk further?

Aside from the treatment of LDL-C, not much progress has been made in the treatment of hypertriglyceridemia and low HDL-C. The management of extreme high triglycerides probably caused by various genetic etiologies is still difficult. The development of HDL-C raising drugs, such as CETP inhibitors has not been always successful. Nonetheless, a recent trial of IL-1β inhibitor targeting on the inflammatory pathway shed light on the reduction of residual CV risk beyond lipid lowering therapy.

Future exploration of the science and the clinical management of the residual CV risk in the future is expected to be very exciting!

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Abstract SE6-2

PCSK9 INHIBITORS, A NEW THERAPEUTIC REGIMEN FOR PATIENTS WITH DYSLIPIDEMIA- FROM JAPAN’S PERSPECTIVE MASATO ODAWARA The Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University

Diabetes is a major risk factor for cardiovascular diseases (CVD) and vulnerable plaques associated with dyslipidemia are less likely to regress in patients with diabetes.The Japan Atherosclerosis Society Guideline was revised in 2017, which recommend the reduction of LDLcholesterol (LDL-C) below 70 mg/dLin diabetic patients associated with additional risk factor.

The claims database analysis in Japan, however, showed low achievement rate of LDL-C goal in a CVhigh risk population in a routine care setting. Alirocumab,a PCSK9 inhibitor, has been shown to be safeand highly effective in Japanese population in Phase 3 trial,ODYSSEY Japan and has been on the market since July, 2016.

In this symposium, I would like to discussthe value of alirocumabas a new therapeutic regimen for the management of dyslipidemia from Japan perspective.

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SE6-3

THE ROLE OF PCSK9 INHIBITORS FOR LDL-C REDUCTION IN DIABETIC PATIENT WITH ASCVD- FROM ENDOCRINOLOGIST POINT OF VIEW HORNG-YIH OU Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan City, Taiwan, ROC

Patients with type 2 diabetes have increased cardiovascular risk. Individuals with type 2 diabetes often have elevated levels of non-high-density lipoprotein cholesterol, triglycerides, and small, dense low-density lipoprotein, which further increase their cardiovascular risk.

Statin therapy is commonly used to manage dyslipidaemia, particularly with the goal of reducing LDL-C and non-HDL-C levels. Although significant reductions in cardiovascular events have been observed in individuals with diabetes treated with statins, real-world studies often report underutilisation of statins and suboptimal dosing in high-risk patients. Even with maximally tolerated statin, many diabetic patients continue to have persistent lipid abnormalities, and are therefore exposed to residual cardiovascular risk.

PCSk9 inhibitor is a new class of lipid-lowering agent which showed significant benefit in reducing LDL cholesterol and cardiovascular outcomes in high-risk patients, but specific efficacy for patients with diabetes is unknown. It is until recently that PCSK9 inhibitor’s LDL-reduction effect been reported in diabetic patients. In this talk, the focus will be on the efficacy and safety of PCSK9 inhibitor, alirocumab, in randomized trials of diabetic patients (ODYSSEY DM-insulin and ODYSSEY-DM-Dyslipidemia). These studies prove the primary efficacy endpoints on reductions of LDL (ODYSSEY DM-insulin) and non-HDL cholesterol (ODYSSEY-DM-Dyslipidemia) as expected, without alterations in glycemia. Further validation of PCSK9 inhibitor regarding MACE outcome reductions will be promising to reduce cardiovascular risk in diabetes.

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Abstract SE6-4 EVIDENCE-BASED PCSK9 INHIBITORS: FROM BENCH TO CLINIC AND ITS PROSPECT WEI-WEN LIN Cardiovascular center, Taichung Veteran Hospital, Taichung, Taiwan

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have been approved by FDA for the treatment of high risk cardiovascular disease patients with inadequately treated levels of LDL-C. They are capable of lowering LDL-C by as much as 60 percent in patients on statin therapy.

PCSK9 binds to LDL-R on the surface of hepatocytes, leading to the degradation of the LDL-R and higher levels. Antibodies to PCSK9 interfere with its binding of the LDL-R leading to higher hepatic LDL-R expression and lower plasma LDL-C levels. Alirocumab and evolocumab are fully humanized monoclonal antibodies approved for clinical used.

Following an initial subcutaneous injection of PCSK9i, the onset of inactivation of PCSK9 enzyme occurs within four to eight hours following the first subcutaneous injection, elimination is expected to occur via saturable binding to PCSK9 enzyme and nonsaturable proteolysis to small peptides and amino acids. The effective elimination half-life of the available PCSK9 inhibitors is 11 to 20 days. PCSK9i studies are landmark trials providing formal evidence that treatment targeted at PCSK9 receptor confers additional cardiovascular benefit beyond that achieved by lipid-lowering treatment alone. The side effects of treatment with monoclonal antibodies against PCSK9 appear to be generally mild but are being meticulously evaluated in separate sub studies. It is anticipated that the results of the PCSK9i trial will soon be implemented in international guidelines regarding the treatment of high-risk patients, directing clinicians in the use of this new and expensive class of drugs.

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SD1-1 FRAILTY AND SARCOPENIA IN OLDER ADULTS WITH DIABETES LIANG-KUNG CHEN Aging and Health Research Center, National Yang Ming University Center for Geriatrics and Gerontology, Taipei Veterans General Hospital

Diabetes mellitus is a prevalent condition of older adults, and the management may differ greatly from younger counterpart. The epidemiological study clearly showed that disability and dementia may be strong predictors than multimorbidity for adverse health outcomes in older people, which highlights the importance of prevention for disability and dementia. In particular, frailty and sarcopenia are two major foci to prevent disability.

Sarcopenia, so-defined as the age-related loss of muscle mass plus loss of muscle strength and/ or loss of physical performance, is a newly defined disease entity. Age-related changes in body compostion is featured by the loss of bone mass, muscle mass and increase of fat mass. Nevertheless, sarcopenia is never a normal aging process, which is associated with mortality and morbidity.

Diabetes, frailty and sarcopenia are highly interrelated conditions in older populations. Chronic inflammation and altered energy metabolism of cardiometabolic disease may accelerate muscle wasting. On the other hand, sarcopenia is also associated with higher risk of diabetes due to the loss of mitochondria.

In modern clinical practice, adding consideration of disability and dementia into diabetes care is of critical importance. On the other hand, more attentions should be paid to diabetes patients with frailty and/or sarcopenia.

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Abstract SD1-2 COGNITIVE IMPAIRMENT AND DIABETES: RECIPROCAL RELATIONS AND CLINICAL IMPLICATIONS PEI-NING WANG Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan

There is evidence of the association between diabetes, cognitive decline and dementia. The duration of diabetes, glycated hemoglobin levels and glycemic fluctuations were associated with cognitive decline and dementia. Furthermore, diabetes not only increases the risk of vascular dementia but also Alzheimer’s disease (AD).

AD is the most common type of dementia that is characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Correspondingly, hypoglycemia was significantly related to increased risk of developing cognitive decline and dementia. Acute or severe hypoglycemia, i.e., depriving the brain of glucose, is associated with neuronal damage in the hippocampus and cerebral cortex. Hypoglycemia is a frequent clinical situation in the strict management of diabetes and is well known as an important factor that directly affects the risk of dementia and cognitive impairment. In patients aged ≥65 years with type 2 diabetes, higher glucose variability and lower average glucose levels are noted and indicate a greater hypoglycemia risk. Elderly patients with T2DM combined with AD may benefit more from the moderate control of blood glucose and a proper increase of the target value.

There are some studies and clinical trials showed the types of anti-diabetic treatment may have influence in the protection of cognition decline in patients with type 2 diabetes. However, the recent Cochrane review found no good evidence that any specific treatment or treatment strategy for Type 2 diabetes can prevent or delay cognitive impairment.

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SD2-1 INTRODUCTION OF DAROC CLINICAL PRACTICE GUIDELINES FOR DIABETES CARE- 2018 HUNG-YUAN LI Department of Internal Medicine, National Taiwan University Hospital

Based on the findings of various reports, it is estimated that there were 1.73-2.20 million people with treated diabetes in Taiwan in 2014-2015. There is no change in the diagnostic criteria for diabetes, which can be made by fasting plasma glucose, 2-hour plasma glucose during a 75g oral glucose tolerance test and hemoglobin A1c. Physicians can differentiate type 1 and type 2 diabetes by clinical presentation, plasma c-peptide concentration, the presence of auto-antibodies and treatment response.

Gestational diabetes mellitus can be diagnosed by “one-step” method using 75g oral glucose tolerance test or by “two-step” method using 50g glucose challenge test followed by 100g oral glucose tolerance test. There are 3 different screening methods suggested by the guideline. One is based on the service by the National Health Insurance in Taiwan, one is based on Taiwan Diabetes Risk Scores, and the other one is based on risk factors of diabetes. For these high-risk groups, results from fasting plasma glucose and hemoglobin A1c can be used to determine the need of an oral glucose tolerance test.

Generally, the treatment goals for adults with diabetes are fasting plasma glucose 80-130 mg/dL, post-prandial plasma glucose 80-160 mg/dL and hemoglobin A1c < 7%. However, these goals should be individualized. For the older adults, less stringent treatment goals can be set according to their health status. For children and adolescents with type 1 diabetes, the general treatment goals are fasting plasma glucose 90-130 mg/dL, plasma glucose before sleep 90-150 mg/dL and hemoglobin A1c < 7.5%, with individualized considerations. For women with gestational diabetes, the treatment goals are fasting plasma glucose < 95 mg/dL, 1-hour post-prandial plasma glucose < 140 mg/dL, 2-hour postprandial plasma glucose < 120 mg/dL and glycated albumin < 15.8%.

The guideline recommend a treatment algorithm for people with type 2 diabetes. Physicians should consider patient’s current glycemic control, risk of hypoglycemia, body weight, risk of cardiovascular diseases and adverse effect, in order to determine the appropriate pharmacological therapy for the patient. Besides, regular monitoring is recommended, which includes plasma glucose, hemoglobin A1c, lipid profile, renal function, the presence of diabetic complications including retinopathy, nephropathy, neuropathy and diabetic foot diseases, oral examinations, and screening for cancers. For diabetic inpatients, the general glycemic control is plasma glucose 140-180 mg/dL. Individual consideration is needed for a more or less stringent goal.

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Abstract SD2-2 2018 DAROC CLINICAL PRACTICE GUIDELINES FOR DIABETES CARE--THE DIAGNOSIS AND TREATMENT FOR DIABETES IN PREGNANCY CHUN-HENG KUO Division of Endocrine & Metabolism, New Taipei City Hospital, New Taipei City, Taiwan, ROC

For many years, gestational diabetes mellitus (GDM) is diagnosed by two-step strategy, using a nonfasting 1-hour 50g glucose load test (GLT) screen, followed by a 3-hour 100g oral glucose tolerance test (OGTT) for those who screen positive. In 2008, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study found that plasma glucose values during a 2-hour 75g OGTT can predict adverse pregnancy outcomes, including increased frequency of birth weight, cord serum C-peptide levels, and infant adiposity > 90th percentile. This is the first outcome-based large scale study to provide evidence-based clinical judgment to diagnose GDM. Based on the findings, the International Association of the Diabetes and Pregnancy Study Group (IADPSG) proposed new diagnostic criteria using one-step approach by a 2-hour 75g OGTT to screen all pregnant women, which was adopted by many organizations including the World Health Organization (WHO) and the American Diabetes Association (ADA).

In 2018 DAROC guidelines, we adopted ADA diagnostic criteria for GDM, which can be accomplished with either one-step or two-step approach. Besides, screening for preexisting diabetes mellitus (PDM) was also recommended for all pregnant women at the first prenatal visit. By definition, diabetes in pregnancy (DIP) can be classified as PDM or GDM. Since treatment would reduce the adverse perinatal outcomes, it should be initiated soon after the diagnosis of DIP. All pregnant women diagnosed with DIP were recommended to receive nutrition and exercise counseling. Most women diagnosed with GDM would achieve glycemic targets by lifestyle modification alone. For PDM women or GDM women who cannot achieve glycemic goals, pharmacologic therapies should be given. Insulin is the first-line regimen recommended for treatment of both PDM and GDM. Metformin and glyburide can be used for the treatment of GDM although the long-term safety trials for both medications are not available yet.

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SD2-3

THE EVOLUTION OF DIABETES MANAGEMENT (SGLT2I + GLP-1 RA + TOUJEO/DEGLUDEC + CGM) CHIH-HSUN CHU Division of Endocrinology and Metabolism, Department of Medicine, Kaohsiung Veterans General Hospital, Taiwan

Antidiabetic medications include oral antidiabetic agents and injectable agents (insulin and GLP1 RA). Metformin is always the first line medication. In dual therapy the medications with evidences to reduce cardiovascular events or mortality should be considered in patients with atherosclerotic cardiovascular disease. The antidiabetic medications proved to have cardiovascular benefit include SGLT2i and GLP-1 RA. The novel long-acting basal insulin analogues (Toujeo/degludec) have evidence to reduce hypoglycemia. Though high costs of analog insulin, they may be a practical option for some patients, and clinicians should be familiar with its use.

The continuous Glucose Monitoring (CGM) is a device that provides continuous insight into glucose levels throughout the day and night. It can help to detect the unaware hypoglycemia or hyperglycemia and to provide additional information with the diabetes management.

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ORAL ANTIHYPERGLYCEMIC THERAPY IN PATIENTS WITH TYPE 2 AND ASCVD – EVIDENCE AND CLINICAL PRACTICE RECOMMENDATIONS JULIANA CHAN Chair Professor of Medicine and Therapeutics and Director, Hong Kong Institute of Diabetes and Obesity and Director, Clinical Research Management Office, The Chinese University of Hong Kong, Prince of Wales Hospital.

The frequent co-existence of obesity, hypertension and dyslipidemia have put people with type 2 diabetes at high risk of cardiovascular-renal disease and premature death. While the use of statins and renin-angiotensin system inhibitors have improved their clinical outcomes, obesity and hyperglycemia contributed to their residual risk for these life threatening events. The new drug classes including incretin therapy and sodium glucose transporter inhibitors (SGLT2i) have provided opportunities to reduce hyperglycemia with low risk of hypoglycemia and weight neutral or reducing effects. The effects of reducing cardiovascular events, renal failure, heart failure and all-cause death with SGLT2i in EMPA-REG and to some extent CANVAS are particularly noteworthy. These trial data were also supported by real-world evidence in more diverse populationsmaking this class of drug an important armamentariumin these high risk patients with suboptimal control. The rapid onset of clinical benefits of SGLT2i raised important questions regarding the pathogenetic roles of abnormal water and sodium homeostasis and haemodilution with ongoing studies in patients with heart failure and chronic kidney disease. Although the neutral effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on cardiovascular outcomes were disappointing, its excellent tolerability in patients with chronic kidney disease and low blood glucose variability with sustained glycemic durability might be translated to long term benefits.

In a meta-analysis, glycemic burden was the main determinant in explaining the cardiovascular benefits in these blood glucose lowering outcome trials and that if glycemic control could be sustained, long term benefits as reported in the UKPDS would be expected. Despite these encouraging results, the challenge lies in closing the huge treatment gaps in this growing population of people with diabetes, especially in young people who face long disease duration. To this end, system change is needed to create a practicing environment which enablesthe care team to systematically phenotype these individuals, reduce clinical inertia and treatment non-adherence in order to reduce these preventable hospitalizations, morbidity and premature death.

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SD3-2

THERAPEUTIC ADVANCES WITHNEW INSULIN ANALOGUE AND GLP-1RA BASED ON RECENT CVOT RESULTS MASATO ODAWARA Affiliation,The Department of Diabetes, Endocrinology, Metabolism and Rheumatology, Tokyo Medical University

Diabetes, a global emergency, is a major risk factor for cardiovascular diseases (CVD). Up to 41% of diabetic patients have a history of CVD and individuals with diabetes are 2 – 4 times more likely to die from CVD than people without diabetes.

Severe hypoglycemia should be avoided based on learnings from the ACCORD and VADT. The sub-analysis of DEVOTE trial confirming cardiovascular safety of insulin degludec vs glargine, has recently shown that higher day-to-day fasting glycemic variability is associated with increased risk of severe hypoglycemia and all-cause mortality. In addition, some GLP-1 receptor agonists (GLP1RA) have been shown to reduce cardiovascular risk in CVOTs, leading to be recommended for type 2 diabetic patients with atherosclerotic cardiovascular diseases (ASCVD) in Standards of Medical Care in Diabetes.

In this symposium, I would like to discuss therapeutic advances of new insulin analogues and GLP-1RAs for diabetic patients with ASCVD based on recent evidence.

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Abstract SD4-1

PROTECTIVE ROLE OF THYROID HORMONE IN LIVER CARCINOGENESIS KWANG-HUEI LIN Department of Biochemistry, Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan

Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showtwo models to elucidate the protect role TH during hepatocarcinogenesis. Depletion of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy related 7)via adeno-associated virus(AAV)vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase),which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protectshepatocytes fromDEN-induced hepatotoxicity or carcinogenesis.

Infection by hepatitis B virus (HBV) accounts for 50~80% of HCC development worldwide, in which the HBV encoded X protein (HBx) plays critical role in the induction of carcinogenesis. Several studies have shown that TH suppresses HCC development and protects hepatocytes from HBx induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of ROS inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted mitochondria simultaneously, consequently leading to suppression of HBxpromoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger 97

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selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicates thatTH/PINK1/Parkin pathway plays a critical role in protecting hepatocytes from HBxinduced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of thyroid hormone facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T3 constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.

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ROLE OF ADIPOCYTE HYPERTROPHY AND HYPOXIA IN THE DEVELOPMENT OF ADIPOSE TISSUE INFLAMMATION AND INSULIN RESISTANCE – THE INVOLVEMENT OF COX-2 ACTIVATION PO-SHIUAN HSIEH Institute of Preventive Medicine, National Defense Medical Center, Taiwan, ROC

Adipose tissue inflammation has been suggested to play a central role in the pathogenesis of many obesity-associated complications including insulin resistance and type 2 diabetes. Adipocyte hypertrophy and hypoxia especially in morbid obesity are the important sources for the development of adipose tissue inflammation. This inflammation is mediated by producing a large number of cytokines and chemokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and regulated upon activation, normal T-cell expressed and secreted (RANTES). Of note, these cytokines and chemokines produced by adipocytes during hypertrophy and hypoxia are crucially involved in the initiation and development of obesity-associated inflammatory response in adipose tissue. The capacity of constitutive and regulated release of immune mediators from adipocytes demonstrates a causal link between the biology of adipocytes and immune cells, such as macrophages and T cells. Moreover, the synergistic effect of hypertrophic, hypoxia adipocytes, and adipose tissue immune cells has also been implicated in the development of obesity-induced insulin resistance.

Our study provides the supportive evidence to demonstrate the important role of COX2 activation in development of adipocyte hypertrophy and hypoxia in the pathogenesis of obesity associated adipose tissue (AT) inflammation and insulin resistance.

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SD5-1

DIABETIC NEUROPATHY: PERCEPTION BEYOND THE SEAM OF THE PERIPHERY SOLOMON TESFAYE Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield.

Diabetic peripheral neuropathy (DPN) is a common, debilitating and distressing complication of diabetes. Most patients develop painless, insensate distal nerve damage which increases the risk of foot ulceration and subsequent amputation. Amputation is not only devastating in its impact on the person with diabetes and their family, leading to loss of independence and livelihood; it is also very expensive in material terms and results in only 50% surviving for two years. Around a quarter of all diabetic patients also develop a chronic painful condition mainly affecting the legs which can result in considerable disability and suffering. Many such patients with painful DPN have depression, anxiety, fear and stress, and do not sleep well. There is thus an urgent need to detect DPN early by using objective, validated point-of-care devices as clinical exam or the use of the 10 gram monofilament is not reliable. Early detection will lead to an earlier intervention to reduce risk factors for the development of DPN. There has also been emerging evidence that DPN may not be as its name suggest, and may involve the central nervous system. We have reported the involvement of the spinal cord in DPN on MRI. More recently we have reported the involvement of the brain in DPN by demonstrating: 1) thalamic neuronal dysfunction using MR Spectroscopy, 2) increased thalamic vascularity in painful DPN on MR perfusion imaging and disruption of the resting state network connectivity on functional MRI. If we are able to develop non-invasive, objective biomarkers of painful DPN this would be a great advance as it would serve as a target for the development of new drugs for this distressing condition. The symptomatic management of painful DPN continues to pose considerable challenge to clinicians as less than 50% of patients respond to current drugs. Innovative, head-to-head and combination trials of new and existing drugs are required. We have obtained $4.8 m funding from the UK NIHR to conduct such a trial. Finally, there is early evidence that a patient’s pain phenotype may determine response to treatment although further studies are required.

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GLYCEMIC CONTROL FOR PATIENTS WITH CEREBROVASCULAR DISEASE JIANN-SHING JENG Stroke Center & Department of Neurology, National Taiwan University Hospital

Subjects with diabetes mellitus (DM) are at two-to six-fold increased risk of stroke, with the higher risk in young patients or type 1 DM. Data from Taiwan’s National Health Insurance, the incidence of stroke in DM and non-DM was 10.1 and 4.5 per 1000 person-year, respectively, and the hazard ratio was 1.75 (1.64–1.86).Due to yearly increase in DM prevalence in Taiwan, the contribution of DM to stroke is expected to increase gradually. By the Taiwan Stroke Registry during 200608 in 30599 stroke patients, the prevalence of DM in ischemic stroke was 45% and in intracerebral hemorrhage was 37%. Besides, acute stroke patients with DM often have greater stroke severity, more unfavorable functional outcome and mortality, and higher stroke recurrence than those without DM. Admission hyperglycemia is a well-established independent predictor of neurological worsening and poor outcome following stroke.Post-strokehyperglycemia has been associated with increased cytotoxic edema, blood-brain-barrier disruption, hemorrhagic transformation, lower likelihood of recanalization and deteriorating neurological state. Besides, hyperglycemia may decrease the efficacy and increase the hemorrhagic transformation in acute ischemic stroke patients receiving reperfusion therapy. Thus, hyperglycemia in acute stroke may lead to higher stroke severity, more stroke in evolution, poorer functional outcome. While correcting hyperglycemia, great care should be taken to avoid hypoglycemia, and subsequently aggressive insulin administration treatment is not suggested.For most patients, the goal of regular treatment is euglycemia and for acute-stroke patients, a reasonable approach is to target control of glucose level at 100-150 mg/dL. Newer glucose-lowering agents, including thiazolidinediones, GLT-1 agonists and SGLT-2 inhibitors have shown decrease in the risk of cardiovascular events in recent randomized, placebo controlled trials. Of these, semaglutide showed reduced the risk of ischemic stroke. Except for glucose lowering effect, the cardiovascular benefit might be due to body weight and blood pressure reduction which are also important for stroke prevention.

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GROWING CHALLENGE OF DIABETIC NEPHROPATHY DAISUKE KOYA Division of Diabetology & Endocrinology, Kanazawa Medical University

Diabetic nephropathy is not only a leading cause of end stage renal disease (ESRD), but also associated with higher risk of ASCVD. Tight blood glucose and bold pressure control with RAS inhibitors have shown to reduce the development and progression of diabetic nephropathy. However, renal hard events defined by doubling of sCr and/or ESRD remain unsolved yet. Here, we talk about the promising effects of DPP-4 inhibitor on the progression of diabetic nephropathy as well as the crucial effects of SGLT2 inhibitors on renal hard endpoints.

Three randomized clinical trials with DPP-4 inhibitors failed to show the beneficial effects on 3-point MACE. However, treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial saxagliptin in the SAVOR-TIMI 53 Trial.

We have also reported that the switching other DDP-4 inhibitors toanagliptin was associated with improvement of albuminuria as well as tubular injury defined by urinary L-FABP in type 2 diabetic patients with albuminuria>30mg/gCrindependent on glucose control. Indeed, we have revealed the underlying mechanism of DPP-4 inhibitor by which resolved diabetes-induced renal fibrosis possibly through the inhibition of endothelial-mesenchymal transition in type 1 diabetic mice.

Surprisingly, SGLT2 inhibitors such as empagliflozin and canagliflozin has shown to prevent the development of ESRD defined by sustained 40% loss of eGFR and/or doubling of sCr, renal replacement therapy, and renal death in EMPA-REG Outcome and CANVAS program in addition to reduction of 3-point MACE, CV death, and total mortality although type 2 diabetic patients with CKD defined by albuminuria and eGFR< 60ml/min/1.73 m2 were about 30% of all precipitants.

Other SGLT2 inhibitors have also demonstrated the renoprotective effects in type 2 diabetic patients.

Mechanistically, SGLT2 inhibitors reverse diabetes-induced hemodynamic alteration by normalization of tubuloglomerular feedbackand also protect against higher glucose and sodium-dependent tubular injuries.

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GLUCOSE CONTROL IN DIABETIC PATIENTS WITH MODERATE AND ADVANCED KIDNEY DISEASE 林俊良 嘉義長庚醫院內科教授

Chronic kidney disease (CKD) is associated with insulin resistance and, in advanced CKD, decreased insulin degradation. The latter can lead to a marked decrease in insulin requirement or even the cessation of insulin therapy in patients with type 2 diabetes. Both of these abnormalities are at least partially reversed with the institution of dialysis. Because of the uncertainty in predicting insulin requirements, careful individualized therapy is essential among patients who have advanced CKD or are initiating dialysis. This lecture will review glycemic targets, methods of monitoring glycemic control, and suggested treatment regimens for patients on CKD, hemodialysis and peritoneal dialysis. The treatment of nondialysis CKD and dialysis patients with diabetes involves both nonpharmacologic and pharmacologic therapies. The nonpharmacologic therapies include dietary modification, exercise, and weight reduction. Pharmacologic therapies include insulin and oral agents. Our pharmacologic approach varies depending upon whether patients have predialysis CKD or are on dialysis. For most hemodialysis patients with type 2 diabetes, we suggest initial treatment with insulin, rather than oral agents Some clinicians prefer to use oral agents rather than insulin, especially among patients who have already achieved acceptable glycemic control on these agents. If an oral agent is used, the preferred agents are glipizide or repaglinide. For peritoneal dialysis patients with type 2 diabetes who were already on an oral agent with good glycemic control prior to starting dialysis and for patients who develop diabetes after starting dialysis, we suggest using an oral agent, rather than insulin. For PD patients, we suggest the use of subcutaneous, rather than intraperitoneal, insulin. Severe hyperglycemia may be observed among dialysis patients with diabetes. Instead of fluid replacement, management is principally dependent upon the administration of low doses of intravenous insulin.

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YL-1

THE ROLE OF PGE2 METABOLISM IN THE PATHOGENESIS OF DIABETIC KIDNEY DISEASE CHIH-HUNG LIN Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan

Diabetic kidney disease (DKD) is one of the most common complications of diabetes. The pathogenesis is very sophisticated, involving many unique albeit inter-correlated cell types and mechanisms. Despite the efforts and recent progress in treating diabetes, deterioration of renal function is still inevitable in certain patients. Such condition emphasizes the necessity of further investigation of this disease.

Prostaglandins (PGs) play important parts in the maintenance of homoeostasis and the pathogenesis of various diseases. Many studies have proposed the roles of different PGs in the pathogenesis of DKD. As the major renal metabolite, PGE2 seems to have both protective and hazardous effects on the kidney via different EP receptors. On the contrary, knowledge about the effect of metabolism of PGE2 on DKD is still very limited.

PGE 2 is a mediator with short half-life. It is catabolized by NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) into 15-keto-PGE2, followed by prostaglandin reductase 2 (PTGR2), which further catalyzes 15-keto-PGE2 into 13,14-dihydro-15-keto-PGE2. Little is known about the pathophysiological functions of these PGE2-catabolizing enzymes. One intriguing fact is that the metabolites of PG might have reno-protective potential. Thus, the aim of the present study is to elucidate the role of PGE2 metabolism in the pathogenesis of DKD. By manipulating the expression of PTGR2, its effects on various phenotypes of DKD are examined.

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MOLECULAR MECHANISM BY WHICH MATERNALLY INHERITED MITOCHONDRIAL DYSFUNCTION CAUSES INSULIN RESISTANCE YI-CHENG CHANG Department of Internal Medicine, National Taiwan University Hospital

Type 2 diabetes is a major threat to global health. The main pathophysiological feature of type 2 diabetes is insulin resistance. However, the underlying cause by which insulin resistance develops is still not fully elucidated. In past human studies, a strong correlation between mitochondrial dysfunction and insulin resistance has been observed. Nevertheless, the casual relationship and the molecular mechanism remained to be explored.

SUV3 is a conserved nuclear-encoded mitochondrial RNA helicase, a component of mitochondrial RNA degradesome. SUV3 is essential for mitochondrial RNA homeostasis. In mammalian cells, deficiency of SUV3 causes mitochondrial RNA accumulation, DNA instability, reduction of mitochondrial copy number, and lower respiration. Deficiency of SUV3 in mice cause accelerated mitochondrial DNA mutation, reduced mitochondrial DNA copy numbers, and mitochondrial dysfunction. These phenotypes could be maternally inherited.

We found that mice carrying defective mitochondrial through maternal inheritance developed glucose intolerance and insulin resistance, accompanied with elevated free fatty acid and exercise intolerance. Indirect calorimetry indicated lower fatty acid oxidation rate of these mice. Transcriptome analysis showed that pathways involved in DNA repair and insulin signaling is significantly reduced in skeletal muscle of these mice. These data strongly indicate that maternally inherited mitochondrial function reduces insulin signaling in skeletal muscle. Preliminary analysis of mitochondrial genome using next-generation sequencing showed a trend of increased mutation load as compared to controls.

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THE RELATIONSHIP OF AMYLIN AND NEW-ONET DIABETES MELLITUS AND OBESITY KANG-CHIH FAN Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan Unuversity Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan, ROC

Type 2 diabetes mellitus is one of the most common diseases in the world and could lead to multiple complications to the patients such as cardiovascular disease, neuropathy, nephropathy and retinopathy. As we know,insulin resistance is one of the major pathogenesis in type 2 diabetes mellitus. In addition to insulin, multiple hormones participate in glucose regulation and homeostasis including amylin. Amylin (IAPP, islet amyloid polypeptide) is a 37-amino acid peptide that is stored in pancreatic β-cells and is co-secreted with insulin. Amylin affects glucose control through several mechanisms, including slowed gastric emptying, regulation of postprandial glucagon, and reduction of food intake. Decreased amylin level in blood was observed in patients with type 2 diabetes and type 1 diabetes according to previously clinical study. However, islet amyloid poypeptide aggregates to form islet amyloid in type 2 diabetes. Islet amyloid formation contributes to β-cells dysfunction and death.

Studies in rat model transgenic for human-islet amyloid polypeptide revealed toxic effect onβ-cells apoptosis and insulin resistance. As a result, the role of amylin in the pathogenesis of diabetes is worth of studying based on our cohort study database.

Overweight is one of the common risk factors amoung patients of type 2 diabetes. The Adipose tissue in obesity patients would promote inflammatory mediators production including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-a and interleukin-6. These inflammatory response may contribute to the increased risk for type 2 diabetes and affect the expression of adipocytokines. As a result, the relationships between amylin and obesity is one of the important issues in the field of diabetes and obesity.

Therefore, in the present study, we will use a longitudinal cohort study to analyze the relationship between plasma amylin level and new-onset diabetes mellitus and obesity. Our cohort, named Taiwan Lifestyle Study, is a community-based study, which enrolled residents from the Yunlin County, Taiwan,aged over 18 years old, who did not report the presence of diabetesduring an interview, were invited to join this prospective study from 2006 to 2012. There were 3 visits forthis prospective study, separated by 1 to 3 years.Individuals receivedquestionnaire, physical examination including blood pressure, body weight, height, waist circumference, hip circumference by trained nurses. We also conducted blood examination for estimation of biochemical, metabolic and oral glucose tolerance test, TG, high and low density cholesterol, adiponectin, leptinand insulin resistance. Abdominal computed tomography exam was also performed during follow up visit to quantify the abdominal fat tissue.

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Abstract After follow up, about 60 people developed new-onset diabetes mellitus amoung 432 individuals.

Diagnosis of diabetes mellitus is according to the definition of American Diabetes Association (ADA), determined by using the history of medications and the result of oral glucose tolerance test. We will measure fasting and postprandial (2 hrs) plasma amylin concentration to clarity its relationship with new-onset diabetes mellitus. Pearson’s correlation coefficient will be applied to elucidate the relationship between plasma amylin concentration and clinical characteristics such as abdominal fat by computed tomography, plasma adiponectin and leptin level. The Cox proportional hazard model will be applied to analyze whether low plasma amylin concentration is one of the risk factors for new-onset diabetes mellitus by adjusting confounders, including age, sex, BMI, family history, fasting glucose, fasting insulin and insulin sensitivity.

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YL-4

THE LINKAGE BETWEEN FNDC5/IRISIN, INSULIN SECRETION AND BETA CELLS PROLIFERATION ON ISLET IN OBESITY AND HYPERGLYCEMIA CHUNG-ZE WU Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei, Medical University, Taipei, Taiwan, R.O.C

Irisin was recently identified as muscle-derived factor that release from muscle immediately after exercise. It is secreted from fibrinectin type III domain containing 5 (FNDC5) after the cleavage if its extracellular portion. A large bundle of studies showed irisin is associated with regulation of glucose homeostasis. In addition, irisin expression in islet was noted. However, there is few study explored the role of irisin on insulin secretion and development diabetes mellitus. In cell model, murine β cells, NIT-1 cells, were treated with normal glucose (7mM) or high glucose (25mM) for 24 or 48 hours.

Culture medium were collected and irisin levels were measured by irisin ELISA. Western blot was performed for assessing intracellular FNDC5 expression in β cells. Moreover, insulin secretion rate of NIT-1 cells in normal or high glucose stimulation were assessed with after silencing FNDC5 by siRNA. In mouse model, C57B6/J and BALB/c mice were fed with chow diet and high fat diet (40%) respectively. Immunohistochemical (IHC) stains of FNDC5 on islet in each group were assessed.

Irisin secretion of NIT-1 cells declined after treating with high glucose compared with normal glucose after adjust cellular proliferation. At the same time, FNDC5 intracellular expression also declined after treating with high glucose. After silencing FNDC5 by siRNA, insulin secretion rate of NIT-1 cells showed significant decelerated after treating with high glucose, but no significant difference in normal glucose. High glucose inhibits irisin excretion and FNDC5 intracellular expression on β cells.

Deficiency of FNDC5 impairs insulin secretion of β cells in high glucose challenge. In high fat diet mouse, expression of FNDC5 showed no significant difference from control mouse. However, FNDC5 expression on islet showed declination in diabetic mouse model. Accordingly, FNDC5 and irisin may play an important role on insulin secretion.

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THE HEPATIC PROTECTION EFFECTS OF HEPASSOCIN IN HYPERGLYCEMIC CRISIS HORNG-YIH OU Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Background: High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes and also exerts protective activity in liver injury.

However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown.

Objective: To investigate the possible hepatic protection effects of hepassocin in hyperglycemic crisis.

Methods: Plasma hepassocin concentrations and routine biochemistry were measured in 21 patients with hyperglycemic crisis before and after standard treatments. The effects of hepassocin on hepatic functions were evaluated in streptozotocin-induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the possible mechanisms regulating hepassocin expression.

Results: Plasma hepassocin concentrations decreased significantly in subjects with hyperglycemic crisis after standard treatment accompanied by improved hepatic functions. Correction of hyperglycemia in STZ mice also decreased the hepatic hepassocin expression. Injection of recombinant hepassocin improved hepatic functions and histologic changes and increased the expression of antioxidative stress proteins, including superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin expression through signal transducer and activator of transcription 3 and hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin increased SOD1 expression through an extracellular signal-regulated kinase 1/2 nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate-induced ROS production and improving cell viability.

Conclusions: Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes.

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AP-2

EFFICACY OF AN HSP90 INHIBITOR, GANETESPIB, IN PRECLINICAL THYROID CANCER MODELS 1

SHU-FU LIN, 1JEN-DER LIN, 2CHUEN HSUEH, 3,7TING-CHAO CHOU, 4CHUN-NAN YEH, 5MING-HUANG CHEN,6RICHARD J. WONG 1

Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

Department of Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 3Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 4Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 5Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 6Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 7Current address: PD Science, Inc., Paramus, NJ, USA 2

Heat shock protein 90 is a molecular chaperon that maintains the correct foldingand function of multiple client proteins. The inhibition of heat shock protein 90, whichleads to the simultaneous degradation of multiple proteins involved in oncogenicsignaling pathways, has revealed an innovative strategy to treat a variety of cancertypes. We evaluated the therapeutic effects of ganetespib, a heat shock protein 90inhibitor, in treating thyroid cancer. Ganetespib effectively inhibited cell proliferationin a dose-dependent manner in eight cell lines originating from four major histologictypes of thyroid cancer (papillary, follicular, anaplastic and medullary). Ganetespibdecreased cyclindependent kinase 1 and arrested cell cycle progression in G2/Mphase. The expression of proteins involved in RAS/RAF/ERK and PI3K/AKT/mTORsignaling pathways was also inhibited. The RET level was decreased in a medullarythyroid cancer cell line. Ganetespib increased Bim expression, activated caspase-3 andinduced apoptosis. In vivo, ganetespib retarded the tumor growth of anaplastic andmedullary thyroid cancer xenografts with acceptable safety profiles. These findingsindicate that ganetespib has potential in the treatment of patients with thyroid cancer

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Abstract AP-3

LOWER RISK OF DEMENTIA WITH PIOGLITAZONE,COMPARED WITH OTHER SECOND-LINE TREATMENTS,IN METFORMIN-BASED DUAL THERAPY:A POPULATION-BASED LONGITUDINAL STUDY 1,2,3

CHIEH-HSIANG LU,4CHEN-YI YANG, 5,6CHUNG-YI LI,7CHENG-YANG HSIEH, 4,8,9 HUANG-TZ OU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan. 2College of Chinese Medicine, China Medical University, Taichung, Taiwan. 3Department of Biotechnology, Asia University, Taichung, Taiwan. 4Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University. 5Department of Public Health, College of Medicine, National Cheng Kung University. 6Department of Public Health, China Medical University, Taichung, Taiwan. 7Department of Neurology, Tainan Sin Lau Hospital, Tainan. 8Department of Pharmacy, College of Medicine, National Cheng Kung University, Tainan. 9Department of Pharmacy, National Cheng Kung University Hospital, Tainan.

OBJECTIVE: The effect of pioglitazone was compared with that of other second-line glucoselowering drugs on the risk of dementia among individuals with type 2 diabetes receiving metforminbased dual therapy.

METHODS: A total of 204,323 individuals with type 2 diabetes aged ≥18 years who were stable metformin users and dementia-free before the initiation of second-line glucose-lowering medication were identified in the period 2000-2011 from Taiwan’s National Health Insurance Research Database and followed to the end of 2013. Primary analyses included 51,415 individuals aged ≥65 years without dementia events in the first year of second-line glucose-lowering treatment. Study subjects were classified into mutually exclusive groups according to various second-line glucose-lowering drugs to metformin. Cox proportional hazards models were applied to assess the time-to-event between propensity score-matched glucose-lowering treatment groups.

RESULTS: Individuals aged ≥ 65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors). Among individuals aged ≥18 years, there was also a decreased risk of dementia in those taking pioglitazone compared with those taking other second-line glucoselowering drugs. A lower incidence of dementia was found in users of metformin + pioglitazone compared with users of metformin + rosiglitazone.

CONCLUSION: Pioglitazone as a second-line treatment after metformin might provide a protective effect on dementia risk among individuals with type 2 diabetes.

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AP-4

USEFULNESS OF THE PLASMA GLUCOSE CONCENTRATIONTO-HBA1C RATIO IN PREDICTING CLINICAL OUTCOMES DURING ACUTE ILLNESS WITH EXTREME HYPERGLYCEMIA Y-W SUa, C-Y HSUb, Y-W GUOc, H-S CHENa a

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; b Division of Cardiology and Cardiovascular Research Center, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwna; c Department of Medicine, Taipei City Hospital, Zhongxing Branch, Taipei, Taiwan

Aims- To evaluate the correlation between the plasma glucose-to-glycated haemoglobin ratio(GAR) and clinical outcome during acute illness.

Methods- This retrospective observational cohort study enrolled 661 patients who visited the emergency department of our hospital between 1 July 2008 and 30 September 2010 with plasma glucose concentration > 500mg/dL. Systolic blood pressure, heart rate, white blood cells, neutrophils, haematocrit, blood urea nitrogen, serum creatinine, liver function and plasma glucose concentration were recorded at the initial presentation to the emergency department. Data on glycated haemoglobin over the preceding 6 months were reviewed from our hospital database. The glucose-to-HbA1c ratio (GAR)was calculated as the plasma glucose concentration divided by glycated haemoglobin.

Results- The GAR of those who died was significantly higher than that of the survivors (81.0 ± 25.9 vs. 67.6 ± 25.0; p < 0.001 ). There was a trend toward a higher 90-day mortality rate in patients with higher GARs (log-rank test p < 0.001 for trend). On multivariate Cox regression analysis, the GAR was significantly related to 90-day mortality (hazard ratio[HR] for 1 standard deviation [SD] change:1.41, 95% confidence interval [CI]:1.22-1.63; p < 0.001), but not to plasma glucose. Rates of intensive care unit admission and mechanical ventilator use were also higher in those with higher GARs. Conclusion- GAR independently predicted 90-day mortality, ICU admission and use of patient outcomes than plasma glucose alone in patients with extremely high glucose levels.

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Abstract OE-1

THE SYNERGISTIC EFFECT OF RENALASE AND CHRONIC KIDNEY DISEASE ON ENDOTHELIN-1 IN SUBJECTS WITH ESTABLISHED CORONARY ARTERY DISEASE ‒ A CROSS-SECTIONAL STUDY 1

YU-HSUAN LI, 1WAYNE HUEY-HERNG SHEU, 1WEN-JANE LEE, 1CHIA-PO FU, 1 KAE-WOEI LIANG, 1I-TE LEE Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan

Backgrounds. Endothelin-1 (ET-1), released from endothelium, is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 has been reported to be associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolize catecholamines and regulate blood pressure. Increase in circulating renalase has been reported in the subjects with chronic kidney disease (CKD) and to be associated with coronary artery disease (CAD). We hypothesize a synergistic effect of serum renalase and CKD on serum ET-1 in the subjects with CAD. Methods. A total of 342 non-diabetic subjects with established CAD were included in this study. ET-1 and renalase were measured in all subjects after an over-night fasting. Results. The subjects with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/mL, P < 0.001) and renalase (46.8 ± 17.1 vs. 33.9 ± 9.9 ng/mL, P < 0.001) than those without CKD. The subjects with both CKD and high renalase (> median of 36.2 ng/mL) showed highest serum ET-1 (P value for trend < 0.001). Using multivariate linear regression, high serum renalase with CKD is a significant risk for increase serum ET-1 (95%CI = 0.161‒0.645, P = 0.001). Conclusion. There is synergistic effect of high serum renalase and CKD on increase in ET-1 in the subjects with established CAD.

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OE-2

TREATMENT EFFICACY AND SAFETY OF ULTRASOUND-GUIDED PERCUTANEOUS RADIOFREQUENCY ABLATION FOR BENIGN THYROID NODULES: KCGMH EXPERIENCE 1

CHEN-KAI CHOU, 2SHENG-DEAN LUO, 2WEI-CHIH CHEN, 2YAN-YE SU, 3SHUN-YU CHI, 4WEI-CHE LIN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

OBJECTIVE: To evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) of benign thyroid nodules.

METHODS: From September 2016 to August 2017, we enrolled82patients (74 female, 8male, mean age 44.4 ± 12.3 years) with benign thyroid nodules for a single session of ultrasoundguided percutaneous RFA. The benign nature of all the nodules was confirmed by at least one- time ultrasound-guided core biopsy, and all the patients had normal thyroid functions. The symptomatic score, cosmetic scores and nodule volume of all the patients were recorded before treatment and during 1, 3 and 6 months follow-up.

RESULTS: The RFA procedures were completed with a mean time of 48.6 ± 24.2 min. The procedures were tolerated well in all the patients. Compared to the baseline condition, significant symptomatic and cosmetic score improvement was found in one month, 3 months and 6 months follow-up after RFA. Before RFA, the mean volume for thyroid nodules was 22.1 ± 21.5 cc. At the 1, 3 and 6-month follow-up, the nodule volume mean reduction ratios were 45%, 65% & 70% CONCLUSION: Ultrasound-guided percutaneous RFA seems to be an effective and safe method for the treatment of benign thyroid nodules. It may gain a wide use in clinical practice.

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Abstract OE-3

LOW-DOSE ADEFOVIR THERAPY RELATED OSTEOMALACIA MIMICKING MULTIPLE BONE METASTASIS - A CASE SERIES STUDY 1

SHIH-PENG LIU, 2HAO-CHIH CHANG, 3YI-CHUN LIN

1

Taipei Veterans General Hospital; 2 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital; 3 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital; 4Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

Low-dose adefovir induced osteomalacia is a rare drug adverse effect. It developed insidiously in patients with chronic hepatitis B treated with long term adevofir. As of 2017, no cases have been reported in Taiwan. In this study, we present three cases of low-dose adefovir therapy related osteomalacia, manifested with hypophospatemia and multiple bony fractures. The first case is a 66-year-old female presented with general bone pain and multiple fractures whose bone scan image showed multiple foci of increased uptake mimicked malignant metastasis. However, whole body PETCT reported no evidence of bone metastasis. She was a victim of choric hepatitis B and was taking antiviral therapy of adefovir 10 mg per day since April, 2008. Hyperphosphaturic hypophosphatemia with normal serum fibroblast growth factor-23 (FGF-23) level supported the diagnosis. Symptoms improved after cessation of adefovir and starting oral phosphate supplement. The second is a 76-yearold female with chornic hepatitis B and hepatoma s/p transarterial chemoembolization. She tooked adefovir 20 mg per day for 11 years who also manifested with hyperphosphaturic hypophosphatemia and general bone pain with multi-foci increased uptake on a bone scan image. The third patient is a 56year old male with chronic hepatitis B taking adefovir 10 mg per day for 10 years who sufferred from weight loss with general bone pain and bilateral femur fractures. Hyperphosphaturic hypophosphatemia was also noted while symptoms relieved after discontinuing adefovir and initiating oral phosphate supplement. Although it is rare, it is important that clinicians be aware of this uncommon adverse effect that developed insidiously after long-term adefovir therapy.

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OE-4

A NOVEL MISSENSE MUTATION OF THE MEN1 GENE IN CHINESE FAMILY WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 1

PO-CHIH LIANG, 1YI-HONG ZENG, 2CHEN-WANG CHANG, 1CHUN-CHUAN LEE, 3 PAO-SHU WU, 4CHIA-CHI TSAI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; 3Department of Pathology, MacKay Memorial Hospital and MacKay Medical College, Taipei, Taiwan 4Division of General surgery, Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder which associated with heterozygous germinal mutation of MEN1 tumor suppressor gene. It has a clinical picture of multiple neoplastic disease in at least two of the commonly affected organs : the parathyroid gland, pancreatic islets, pituitary, and adrenal cortex. MEN1 gene, which located on 11q13, comprising 10 exons and exon 2 through 10 encodes the 610-amino acid protein menin.

We report a MEN1 case presenting with pancreatic, adrenal and pituitary tumor, who has a novel missense mutation. Case Report: A 54-year-old female with Type 2 DM, hypertension had received regular follow-up in our hospital. She had complaint of abdominal fullness seven years ago and abdominal ultrasound showed an anechoic lesion about 5.1mm in the pancreatic body. Abdominal computed tomography showed several subcentimeter low densities are found at pancreatic head and body. Tumor markers showed CA-199 (0.25 U/mL) and CEA (1.42 ng/mL). During follow-up with abdominal ultrasound, cyst was gradually increasing in abdominal computed tomography. Endoscopic Ultrasound (EUS) showed multiple anechoic to hypoechoic nodules in the pancreas, size up to 1.3 cm. Fine needle aspiration revealed pancreatic neuroendocrine tumor. In addition, she also had primary hyperparathyroidism, one pituitary microadenoma (5mm) with elevated prolactin(45.58 ng/ mL) and right adrenal non-functioning adenoma. Thus, MEN 1 was diagnosed. Patient then received total pancreatectomy and pathological report showing neuroendocrine tumors, grade 1. Exon-wide sequencing analysis of the MEN1 gene revealed a novel missense mutation at codon 1270 in exon 9, where a guanine residue was exchanged for cytosine (GAG > CAG) and, consequently, glutamic acid for glutamine (p.Glu424Gln; c.1270G > C). The same mutation was identified in her mother.

We conclude that this mutation appeared to be responsible for MEN1 pathogenicity. Conclusion: Nowadays, a total of more than 1800 mutations were characterized. The incidence of neuroendocrine tumor (NET) has increased in the last four decades (from 1.09 to 5.25 per 100,000 individuals between 1973 and 2004) attributed to the improvement of diagnostic imaging, so clinicians should be aware of familial tumor syndrome. However, the lack of genotype-phenotype correlation results in difficulty for clinical investigation and mutational analysis in the diagnosis of MEN1. So we describe a novel missense mutation in the MEN1 gene that caused the MEN1 syndrome.

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Abstract OE-5

EXPERIENCE OF IODINE-131 METAIODOBENZYLGUANIDINE THERAPY OF MALIGNANT PHEOCHROMOCYTOMA IN CCH 1

SZU-HAN LIN, 1SHU-YI WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Metastatic spread is the only true indicator of malignant behavior. Traditional treatments were debulking operation, chemotherapy with CVD regiment (CVD: cyclophosphamide,vincristine and dacarbazine) and/or Iodine-131 Metaiodobenzylguanidine (I-131 MIBG). Tyrosine kinase inhibitor or immunotherapyare ongoing treatment. In our case, a 43-year-old man was diagnosed pheochromocytomas in 2014 with initial presentation of diabetic poor control, intermittent headache, palpitation, sweating and high blood pressure. Abdominal CT revealed a 9.1*5.2cm mass over the right side suprarenal region with mild heterogeneous contrast medium enhance and liver invasion. Function survey showed elevated serum dopamine, nonepinephrine, epinephrine and urine VMA. He accepted adrenalectomy and liver sectomy with adjavant radiotherapy in 2014. However, under regular outpatient department follow, elevated serum nonepinephrine and urine VMA were mentioned. Abdominal CT showed para-aortic lymph node metastases. Malignancy pheochromocytomas was impressed. Chemotherapy CVD regimen and operation of lymph Node dissection were prescribed. However, condition was still progression. He accepted I131-MIBG 150 mCi IV infusion on 2016-11-09 in our hospital. Before the I131-MIBG treatment, patient need accepted lower dose I-131 whole body scan, which could predict treatment response. Patient need to management of excess catecholamines by alpha blockade and protect thyroid by lugol’s solution. Admitted on Day -1 for routine lab data survey and antiemetic ondansetron was prescribed for 3days. During I131-MIBG injection, be care of malignancy hypertension via frequency blood pressure monitor by patient himself. Hydration and frequent voiding were encourage and patient safely discharged on Day3. Follow up whole body scan at Day 7 and lab data showed no neutropenia or thrombocytopenia. Malignancy pheochromocytomas need treatment by multimodality, multidisciplinary and individualized approach. I131-MIBG treatment could be prescribed, but whole course was cost lot. Not only conventional systemic therapies, but some new tyrosine kinase inhibitors (ex. Sunitinib, Cabozantinib) or immune therapy (Pembrolizumab) were ongoing. Need further study in the future.

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OE-6

GENETIC STUDY FOR COMBINED PITUITARY HORMONE DEFICIENCY IN TWO SIBLINGS 1

WEI-LUN WEN, 2WEI-WEN HUNG, 3WEI-CHUN HUNG, 4YI-CHUN TSAI, 1CHIA-WEI LAI, 2PI-JUNG HSIAO, 4SHANG-JYH HWANG 1

Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan, R.O.C; Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan, R.O.C; 3Department of Microbiology and Immunology, Kaohsiung Medical University, Taiwan, R.O.C; 4Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan, R.O.C. 2

Background: In adults, hypopituitarism can occur in women after giving birth as in the case of postpartum hypopituitarism (PPHP). PPHP is associated with intrapartum or postpartum hemorrhage due to coagulation abnormality. Besides, combined pituitary hormone deficiency (CPHD) due to genetic factors can also lead to hypopituitarism, although the onset of CPHD in adulthood is rare. Here we reported hypopituitarism in two siblings and studied for the possible genetic etiology.

Case report and method: Of the two siblings, the younger sister, at the age of 31, was the first to visit our hospital due to failure of lactation after delivering her first baby by Caesarean section.

Her pituitary function tests showed ACTH = 4.36pg/ml, cortisolT (upstream gene variant), c.59G > A (missense mutation) and c.109+3G >A (splice region variant). The last mutation, known to cause CPHD, alters the conserved region of intron 1, and is predicted to cause abnormal splicing of the transcription. In the remaining two genes POU1F1 and HESX1, no mutations were detected.

Discussion: We reported the two siblings diagnosed with postpartum hypopituitarism not related to any coagulation abnormality, but might be associated with genetic factors causing combined pituitary hormone deficiency. Further studies should be carried out in their family members without hypopituitarism to elucidate the mutation of PROP1 as the causative gene leading to hypopituitarism in the two siblings.

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Abstract OD-1

ADAM10 MODULATES CALCITRIOL-REGULATED RAGE IN CARDIOMYOCYTES 1,2

TING-WEI LEE, 1,3YU-HSUN KAO, 2,4TING-I LEE, 1,5YI-JEN CHEN

1

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C; Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C; 3Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C; 4Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C; 5Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C. 2

Background: Receptor for advanced glycation end products (RAGE) signaling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression.

This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes.

Materials and methods: Western blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N-terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL-1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor-κB (NF-κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 hours.

Results: Calcitriol (10 nM) significantly reduced RAGE protein expression and increased sRAGE concentrations in HL-1 cardiomyocytes compared with control cells. These changes were associated with increased protein expression and enzyme activity of ADAM10 and higher mRNA expression of esRAGE. In the presence of ADAM10 inhibitor, however, the suppressive effect of calcitriol on RAGE was diminished. Methylglyoxal (500 μM for 10 min)-mediated JNK phosphorylation was attenuated in the presence of calcitriol (10 nM). Moreover, control and NF-κB inhibitor-treated HL-1 cells had similar RAGE and sRAGE expression, suggesting that calcitriol-mediated RAGE modulation was independent of NF-κB signaling.

Conclusions: We showed that RAGE downregulation and increased sRAGE production by calcitriol was mediated through ADAM10 activation in cardiomyocytes. The results suggest that calcitriol has therapeutic potential in treating RAGE-mediated cardiovascular complications.

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OD-2

THE CHANGE OF THE BONE STRUCTURE AND MICROARCHITECTURE AFTER ORAL ANTIDIABETIC DRUG TREATMENT IN DIET-INDUCED OBESITY MICE 1

CHENG-FENG TSAO, 1JUNG-FU CHEN, 1CHIEN-HUNG KUO, 2SHAO-WEN WENG, 1 PEI-WEN WANG 1

Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Lee’s Endocrinology Clinic, Pingtung, Taiwan

Aims: The therapy of type 2 diabetes mellitus includes lifestyle modification, oral antidiabetic drug and insulin. Pioglitazone has been found associated with decreasing bone mineral density (BMD).

However, the relation between Metformin, sulfonylureas (SU), Empagliflozin and bone structure and microarchitecture remain unclear.

Methods: 1-month-old mice underwent 5 months of treatment course. Mice were fed chow diet (CD), high-fat high-sucrose diet (HFD intervention 2nd-6th month), HFD+Metformin (Metformin intervention 3rd-6th month), HFD+SU (Glimepiride intervention 3rd-6th month), HFD+Empagliflozin (Empagliflozin intervention 3rd-6th month). We compared the different of bone structure and microarchitecture of femoral bone and tibia bone when mice was 6-month-old. The bone structure and microarchitecture was measured by micro computed tomography.

Results: There is no significantly different about BMD of femoral and tibia bone between the CD and the HFD group. The trabecular number of tibia bone of the HFD group, as compared with the CD group, showed decreased. However, the trabecular bone pattern factors, structural model index and trabecular thickness of tibia bone was higher in the HFD group than the CD group. The HFD group showed significantly increased more bone volume/tissue volume, trabecular thickness in femoral bone than the SU group. The HFD group, as compared with Metformin group, had increased bone volume/ tissue volume and decreased total porosity and open porosity in femoral bone. The BMD was not significantly different between the HFD group, the SU group and the Metformin group. The BMD, bone volume, trabecular number, trabecular thickness of tibia bone decreased significantly in the SU group, as compared with the CD group. The open porosity, structure model index of tibia bone in SU group shows more increased significant than the CD group. Besides, the trabecular bone pattern factor decreased less in the SU group than the CD group. The trabecular bone pattern factor of the tibia bone in the Empagliflozin group was higher than the CD group but the trabecular thickness of tibia bone was lower in the Empagliflozin group. Conclusion: The bone microarchitecture of tibia bone decreased more in the HFD group than in the CD group. Interestingly, the trabecular bone microarchitecture, BMD of tibia bone decreased significantly in the SU group in diet-induced obesity mice.

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Abstract OD-3

CHANGES OF GUT MICROBIOTA IN NEWLY-DIAGNOSED TYPE 2 DIABETES TREATED WITH METFORMIN MONOTHERAPY 1

WEI-WEN HUNG, 2WEI-CHUN HUNG, 3YI-CHUN TSAI, 1WEI-LUN WEN, 1HE-JIUN JIANG, 1SHYI-JANG SHIN, 1PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan, R.O.C. 2Department of Microbiology and Immunology, Kaohsiung Medical University, Taiwan, R.O.C. 3Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan, R.O.C.

OBJECTIVE: Current treatment guidelines all over the world suggest metformin as the first-line therapy to treat type 2 diabetes. Despite its use for 60 years, the precise mechanisms of metformin are still not fully discovered. Traditionally, liver was thought to be the main target of metformin action.

More recently, gut has become the center of attention due to the increasing evidences suggesting that the antihypeglycemic effect of metformin is derived from the gut. We aim to evaluate the relation of antihypeglycemic effect and the changes of gut microbiota by metformin in newly-diagnosed and drug-naive type 2 diabetes.

MATERIALS AND METHODS: We recruited 22 patients with newly-diagnosed and drugnaive type 2 diabetes from the outpatient clinic in a university hospital in southern Taiwan. Before and after metformin monotherapy for three months, we collected the biochemical data and measured fecal microbiota by quantitative real-time PCR with 16S rRNA gene sequencing. At the end of three months, there were totally 14 patients continued on metformin monotherapy and completed the collection of stool samples. Wilcoxon signed rank test was used as statistical analysis.

RESULTS: Our results discovered that BMI (body-mass index), HbA1C, and fasting blood glucose decreased and HDL-C increased significantly after metformin monotherapy for three months.

There were no significant changes in cholesterol, triglyceride, LDL-C, HOMA-IR, and UACR (urine albumin/creatinine ratio). Using quantitative real-time PCR with 16S rRNA gene sequencing, we found that Akkermansia and Escherichia increased significantly. The phylum of Firmicutes and Bacteroidetes did not have significant changes after three-month metformin therapy.

DISCUSSION: We revealed that the antihyperglycemic effect of metformin associated with the changes of microbiota including Akkermansia and Escherichia. Understanding the interaction between metformin and gut microbiota in newly-diagnosed type 2 diabetes can help to identify important microbiota species related to the antihypeglycemic effect of metformin. In the future, gut microbiota has the potential to serve as a new therapeutic tool or target in treating type 2 diabetes.

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OD-4

LEVELS OF SERUM HIGH MOBILITY GROUP BOX 1 WERE INDEPENDENTLY ASSOCIATED WITH CARDIOVASCULAR RISK IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY 1

JUN-SING WANG, 1WAYNE H-H SHEU, 2WEN-JANE LEE, 1I-TE LEE, 1SHIH-YI LIN, 3 WEN-LIENG LEE, 3KAE-WOEI LIANG, 4SHING-JONG LIN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan; 4Department of Medical Research; Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The aim of this study was to examine the association of serum high mobility group box 1 (HMGB1) level with cardiovascular risk in patients undergoing coronary angiography with no history of diabetes. Materials and methods: We enrolled patients with no history of diabetes who had been admitted for coronary angiography due to suspected or known coronary artery disease (CAD). Two to four weeks after the patients were discharged from the hospital, an oral glucose tolerance test (OGTT) was conducted and a blood sample was collected for the measurements of glucose, insulin, lipids, and HMGB1. Patients’ glucose regulation status was determined with the results of OGTT. Patients’ 10-year coronary heart disease (CHD) risk was assessed using the Framingham Risk Scoring. Results: A total of 476 patients were included in the analysis (mean age 61 ± 12 years, male 81.9%, mean body mass index 26.1 ± 3.7 kg/m2, CAD 57.8%). Overall, mean serum HMGB1 level was 6.1 ± 1.3 pg/ml. Using linear regression analysis, high-density lipoprotein cholesterol was negatively associated with serum HMGB1 (β coefficient -0.033, 95% CI -0.063 to -0.003, p = 0.033) after adjustment for several confounders. With regard to cardiovascular risk, levels of serum HMGB1 were positively associated with 10-year CHD risk (β coefficient 0.506, 95% CI 0.030 to 0.983, p = 0.037), independent of patients’ undiagnosed abnormal glucose regulation. Conclusions: In patients undergoing coronary angiography with no history of diabetes, levels of serum HMGB1 were positively associated with 10-year CHD risk, independent of patients’ undiagnosed abnormal glucose regulation.

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Abstract OD-5

EVALUATION OF GLYCEMIC CONTROL AND SELF-EFFICACY AMONG PATIENTS RECEIVING CONTINUOUS GLUCOSE MONITORING WITH IMMEDIATE COUNSELING FEEDBACK COMPARED WITH DELAYED COUNSELING FEEDBACK 1,2

YE-FONG DU, 2CHING-JU CHIU, 1HORNG-YIH OU, 1HAO-CHANG HUNG, 1 MING-CHAO LEE 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 2Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Objective To explore the effect of immediate feedback or delayed feedback counseling using professional continuous glucose monitoring (CGM) feedback on glycemic control, self-efficacy, drug compliance, diabetes stress, depression, quality of life and life style among middle aged and older adults with poor controlled type 2 diabetes mellitus.

Method This study enrolled patients aged 45 years and older with HbA1c more than 7%. Participants were assigned into immediate feedback (n = 7) or delayed feedback (n = 10) groups using 4-block randomization design. The immediate feedback group received counseling using CGM graphs on the day of sensor removal. The delayed feedback group received CGM-based counseling 3 months later as usual care schedule. All outcome measures were evaluated at baseline, 3 months, and 6 months.

Results Participants received immediate feedback had lower depression scores (p = 0.024) and better selfefficacy score (p < .001) at 3 months, compared with delayed feedback group, and a better HbA1c level compared with baseline (p = 0.03). Participants at delayed feedback group had an improved MMAS-8 score after receiving CGM-based counseling (p = 0.05) and an improved diabetes stress at 6 months compared with baseline. There was no difference between groups, assessing change of all outcome measures at 3-months after CGM-based feedback counseling.

Conclusion Professional CGM had potential benefit in improving glycemic control, especially if feedback counseling was carried out immediately after sensor removal.

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OD-6

PREVALENCE, INCIDENCE, AND RISK FACTORS OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES - AN 8-YEAR PROSPECTIVE COHORT STUDY IN A COMMUNITY HOSPITAL 1

CHIH-CHENG HSU, 2JIUN-YIAN LIN, 2PI-YUAN WONG, 2I-CHUAN LIN, 2I-JU LIEN, 2 TONG-YUAN TAI 1

Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan ; 2Taipei Jen-Chi Hospital, Taipei, Taiwan

Background. Incidence of sight-threatening diabetic retinopathy (DR) in Taiwan in 2011 estimated by the National Health Insurance Database was 0.6 and 2.2 per 100 person-years for women and men with type 2 diabetes (T2D), respectively. However, the recent epidemiological patterns of ophthalmologist-diagnosed DR in Taiwan are still unknown. This study aimed at assessing DR prevalence, incidence and its attributable factors for community T2D patients.

Methods. We recruited 553 T2D patients from a community hospital in Taipei from 2006 to 2014 and followed them up through December 31, 2014. Pupil-dilated retinal condition was checked by a well-trained ophthalmologist annually. The incidence of DR was calculated by the corresponding events divided by person-years observed. Cox proportional hazards models were used to identify risk factors contributing to development of DR in the follow-up period.

Results. The prevalence of DR at recruitment was 10.7% (7.2% with non-proliferative DR [NPDR] and 3.4% with proliferative DR [PDR]). The incidence of overall DR was 2.25 per 100 person-years. The incidence of PDR for those with NPDR was 3.2 per 100 person-years. The DR incidence for T2D without and with nephropathy was 2.0 and 2.9 per 100 person-years, respectively.

Most significant risk factors contributing to DR were education < 6 years (HR = 2.36, 95% CI = 1.095.09), diabetes onset <45 years of age (HR = 3.62 [1.04-12.61]), diabetes duration ≥ 10 years (HR = 2.43, [1.06-5.56]), nephropathy with eGFR < 45 ml/min (HR = 2.82, [1.00-7.90]), and poor ABC control. Compared with those achieving at least two ABC control criteria (HbA1c < 7%, BP < 140/90 mmHg, and LDL < 100 mg/dL), HR for those with 0 or only 1 good control was 3.48 (1.24-9.76) and 3.76 (1.63-8.66), respectively.

Conclusion. The DR risks include lower education level, earlier diabetes onset and longer diabetes duration. Those with diabetic nephropathy at late stage were more likely to develop retinopathy. For DR prevention, it is essential to control all glucose, blood pressure and cholesterol at an optimal level.

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Abstract PE-1

REPETITIVE SEIZURE AS THE INITIAL PRESENTATION IN A PATIENT WITH PSEUDOHYPOPARATHYROIDISM: A CASE REPORT 1

NIEN-CHU YU, 1,2JIUN-LU LIN, 1,2CHUN-CHUAN LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.

Background: Pseudohypoparathyroidism (PHP) is characteristic by the resistance to parathyroid hormone (PTH) and the resultant hypocalcemia.Albright’s hereditary osteodystrophy (AHO) is anapparent physical feature in patients with PHP-Ia. PHP-Ibpatientspresent predominant renal PTH resistance but lack any features of AHO. Most of PHP patients have defects in GNAS(20q13.3), an imprinted gene locus with multiple transcriptional units.We report one case with repetitive seizures and multiple brain calcification as the presentation of PHP.The patient has typical AHO feature but negative GNAS1 gene test.

Case Report: A 51 year-oldobese, short staturewoman got her body height fixed around 140cm since junior high school and jointspain easily when squatting since teenage. She received full denture due to severe calcification 20 years ago. She also has glaucoma. Her menstrual cycle duration was 4-5 days, interval 28 days, moderate amounts with some dysmenorrhea. She was pregnant three times but lost twice; intrauterine fetal death (IUFD) was diagnosed at her first and third fetus, but the second one grows well until now without any abnormality. She had hospitalization once for infection.

Her first seizure was attacked and treated at Hualien Tzu-Chi Hospital since 20 years ago.Brain CT and MRI showed bilateral globus pallidus, bilateral head of caudate and bilateral cerebellar dentate nucleus calcification. Bilateral hands X-rays found shortening of bilateral 1st, 4th& 5th and left 3rd metacarpal bones and multiple phalangeal bones with bony exostosis. Lab data showed hypocalcemia, hyperphosphatemia, and elevated iPTH level.Subclinical hypothyroidism also noted. GNAS1 gene test was performed due to pseudohypoparathyroidism (PHP) was highly suspected. Now patient under regular Ca supply and OPD follow up Ca &P level.

Discussion: PHP is an idiopathic and inherited form of PTH resistance. Its characteristics are short stature, rounded face, foreshortened fourth and other metacarpals, obesity, and subcutaneous calcification. There are four types of PHP: type 1a, 1b, 1c, and 2. Diagnosis of PHP is defined by the coexistence of hypocalcemia, hyperphosphatemia with elevated PTH levels in the presence of normal Vitamin D value and normal renal function and the absence of hypercalciuria. GNAS1 locus mutation or imprinting abnormalities responsible for PHP different types. The goal of therapy should maintain serum total and ionized Ca level, oral Ca and Vitamin D supply, and prevent morbidity.

Conclusion: We present a case of repetitive seizure as the initial presentation in a patient with pseudohypoparathyroidism. The patient has classic metacarpals and phalanges abnormalities and symptomatic hypocalemia. The diagnosis of PHP requires physician’skeen insight.

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PE-2

CATECHOLAMINE - INDUCED CARDIOMYOPATHY IN A 37 YEAR-OLD WOMAN WITH INITIAL PRESENTATION AS CARDIOGENIC SHOCK 1

YU-PEI LIN, 2CHUN-YAO HUANG, 1CHEN LING HUANG, 4YI-JEN LAI, 1,3 CHUNG-HUEI HSU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 3Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan 4 Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan

Introduction Pheochromocytoma may present as non-specific symptoms that may cause loss of medical alertness initially. In fact, the possibility of excess amount of catecholamine release spontaneously or under stress may lead to severe cardiovascular events or related complications. Case Report The 37 y/o woman he was sent to ER due to sudden onset of palpitation. She also had chest tightness with headache. After admission cardiac echo revealed mild to moderate hypokinesis of LV anterior and apical wall with LVEF =47 %. Thallium scan also revealed no evidence of myocardial ischemia. The patient had mild proptosis and thyroid function showed free T4: 4.24 ng/dl, TSH < 0.05 uIU/ml, TRAb 41.2 % with thyroid echo compatible with Graves’ disease. Methimazloe 10 mg TID with propranolol 10 mg TID were given for treatment. In addition, 24 hr urine cathecholamine and VMA were checked due to recurrent palpitation with dyspnea. However, the patient asked to discharged then. After two weeks later she was sent to ER again due to palpitation with dyspnea.

Her clinical condition get worsen with cold extremities and cyanosis appearance. HR was up to 160 bpm and CXR revealed pulmonary edema. Unstable hemodynamic status was noted then with desaturation and shock. CV doctor was consulted at ER and cardiac echo revealed severe generalized hypokinesis of LV with LVEF = 25 %. Lab data during last admission also revealed elevated 24 hr urine cathcholamine and VMA as: 24 hr urine Norepinephrine 2191.8 ug, 24 hr urine VMA 13.86 mg.

CT was arranged at ER which also showed a 4.5cm well defined heterogenous enhanced mass arised from left side adrenal gland, suspected pheochromocytoma. Under the impression of (1) Cardiogenic shock suspected catecholamine-induced cardiomyopathy related (2) A mass over left adrenal gland suspected pheochromocytoma (3) Graves’ disease under treatment the patient was admitted for further workup and treatment. After admission CVS doctor was consulted for ECMO insertion due to cardiogenic shock. The patient had recovery of consciousness one day later. Repeat cardiac echo in the next morning also showed improved LV contractility. ECMO was weaned after 40 hrs and medication as Doxazosin 1mg BID with Propranolol 10 mg QID given for treatment. The patient also had extubation then due to improved condition. With the impression of pheochromocytoma., urologist was consulted for op evaluation. The patient received left laparoscopic adrenalectomy and the pathology

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Abstract revealed pheochoromocytoma. Cardiac echo follow-up at OPD revealed normal LV chamber size with improving LV anterior wall motion. Conclusion : Patients with a cardiomyopathy, of non-specific origin, should ruled out pheochromocytoma. Catecholamines, especially norepinephrine, can cause a direct toxic effect on the myocardium just like the case above. The mechanism include increased concentration of calcium in the sarcoplasma and increased oxygen demand that induce cardiomyopathy with myocardial necrosis. However, the diagnosis of pheochromocytoma requires high clinical alertness due to variable clinical manifestations. In conclusion, early recognition of catecholamineinduced cardiomyopathy is important for patient with pheochromocytoma to minimize morbidity and mortality rate.

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PE-3

HYPOTHYROIDISM WITH HIGH LEVEL OF FT4 1

HELEN WEI, 1,2CHUN-LAN CHEN, 1,3CHING-CHIEH SU

1

Internal medicine, Cardinal Tien hospital; 2Division of Laboratory, Cardinal Tien hospital; 3Division of endocrinology and metabolism, internal medicine, Cardinal hospital. School of medicine and Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University

59 years old woman came to endocrinology OPD with compliant of goiter for more than one year. Physical examination revealed diffuse goiter with nodular surface and rubbery firm in texture.

Thyroid ultrasound showed diffused goiter with severely heterogeneous hypoechogenicity. Lab test reported free T4 (FT4) 2.08 ng/dl (0.7-1.9), TSH 114.596 mIU/L, anti-thyroglobulin antibody > 2500 (< 60) and thyroperoxidase antibody (TPOAb) >13000 (< 60). Syndrome of inappropriate secretion of TSH (SITSH) or thyrotoxicosis was considered as differential diagnosis. Low dose eltroxin (50 ug/ day) was given initially under the impression of hypothyroidism with unknown cause of high FT4.

Two months later, blood test reported FT4 2.61, T3 109.81ng/dl (80-180) with lower TSH 14.049 and weakly positive TSH receptor antibody 19% (< 10%). Clinical symptoms improved with smaller size of goiter. Eltroxin was added to 500 ug once a week. Follow up two months later, thyroid functional tests reported FT4 3.71, T3 113.91 and TSH 12.753. Eltroxin dosage was increase to 600ug weekly.

The 2-month follow up lab disclosed FT4 4.44, T4 11.3 ug/dl (4.6-12).

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Abstract PE-4

UNDERWEIGHT INCREASES THE RISK OF EARLY DEATH IN TUBERCULOSIS PATIENTS: A POPULATION-BASED STUDY 1

YUNG-FENG YEN, 2FU-I TUNG, 3YUN-JU LAI

1

Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan; 2Section of Orthopedics, Taipei City Hospital, Taipei City Government, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan

Background: Evidence regarding the association between body mass index (BMI) and mortality in tuberculosis (TB) patients is limited and inconsistent. We investigated the impact of BMI on TB-specific and non-TB-specific mortality with respect to different timing of death. Material and method: All Taiwanese adults with TB in Taipei were included in a retrospective cohort study in 2012–2014. Multinomial Cox proportional hazards regression was used to evaluate the associations between BMI, cause-specific mortality, and timing of death. Results: Of 2,410 eligible patients, 86.0% (2061) were successfully treated, and TB-specific and non-TB-specific mortality occurred for 2.2% (54) and 13.9% (335), respectively. After controlling for potential confounders, underweight was significantly associated with a higher risk of all-cause mortality [adjusted hazard ratio (AHR), 1.57; 95% confidence interval (CI), 1.26–1.95], while overweight was not. When cause-specific death was considered, underweight was associated with an increased risk of either TB-specific (AHR, 1.87; 95% CI, 1.04-3.37) or non-TB-specific death (AHR, 1.52; 95% CI, 1.19-1.94) during treatment. With joint consideration of cause-specific and timing of death, underweight only significantly increased the risk of TB-specific (AHR, 2.25; 95% CI, 1.09–4.63) and non-TB-specific mortality (AHR, 1.81; 95% CI, 1.29–2.55) within the first 8 weeks of treatment. Conclusion: This study suggests that underweight increases the risk of early death in TB patients during treatment.

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PE-5

A VERY RARE CASE OF PULMONARY LYMPHANGITIC CARCINOMATOSIS IN PATIENT WITH RECURRENT PAPILLARY THYROID CARCINOMA TSE-YING HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

Papillary thyroid carcinoma (PTC) has been defined as a malignant epithelial tumor showing evidence of follicular cell differentiation. Lung metastases are more frequent in young patients with PTC, and the lung is almost the only site of distant spread in children. Here we present a very rare case of pulmonary lymphangitic carcinomatosis in a 69-year-old man with recurrent papillary thyroid carcinoma. He had initial presentation with painless mass over left supraclavicular fossa, papillary thyroid carcinoma was then diagnosed and he received total thyroidectomy and lymph nodes dissection, with I-131 30mCi was prescribed initially after the first surgical intervention. Four years later, local recurrence was noted and lymph nodes dissection was carried out, without further adjuvant anti-cancer treatment. Two years later, severe cough with blood-tinged sputum developed. The follow up computed tomography (CT) showed recurrent tumor with pulmonary lymphangitic carcinomatosis.

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Abstract PE-6

PITUITARY PLURIHORMONAL ADENOMA SECRETING TSH AND LH –A CASE REPORT 1

YU-YI LIN, 1CHII-MIN HWU, 2WEI-HSIN WANG, 3YU-HUEI LI, 4TZONG-YOE LAI

1

Section of Endocrinology and Metabolism, Department of Internal Medicine,Taipei Veterans General Hospital, Taiwan; 2 Section of Neurosurgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan; 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; 4 Lai’s clinic, Hua-Lien, Taiwan

Background. TSH (Thyrotropin) secreting pituitary adenoma (TSHoma) account for less than 1% of all causes of hyperthyroidism and 1% of all functioning pituitary tumors. Definite diagnosis and treatment of TSHoma are clinical challenge in practice. We report laboratory data, imaging findings, endocrine dynamic test, and treatment outcomes in a 50-year-old Taiwanese man with pituitary adenoma secreting TSH and LH. Case presentation. The patient was initially diagnosed and treated as goiter with primary hyperthyroidism and diabetes mellitus by general clinic doctor in 2014. He received anti-thyroid drug and oral hypoglycemic agent. Two years later, he visited to Endocrinologist’s clinic for poor glycemic control. Central hyperthyroidism was diagnosed due to measurable TSH level in the prescence of increased serum thyroid hormone level. Sella MRI revealed left sided pituitary lesion. He was referred to Taipei Veteran General Hospital for further management.

There was no family history of thyroid disease. Physical examination was not remarkable except diffuse grade 3 goiter and tachycardia (heart rate: 100~115 beat per minute). Laboratory data showed TSH 4.89 uIU/ml, free T4: 3.05 ng/dl, T4: 16.02 μg/dl, T3: 249 ng/dl, free T3: 8.0 pg/ml, normal range of thyroid autoantibodies. Two times of TRH stimulation test showed blunted TSH response. Pituitary hormones level were within normal limit except mild elevation of testosterone 12.69 ng/ml. Sella MRI showed macroadenoma (size 10x10x7.6 mm) at left pituitary gland. Thyroid sonography revealed heterogenous echogenicity with increased size and vascularity of both lobes. I-131 uptake was homogenous uptake (94%). Surgery was performed after one year of definite diagnosis due to personal reason. TSH level returned to normal ranges (0.799 uIU/ml) in 1st post operative day. Histologically, the pituitary mass was compatible with plurihormonal adenoma and immunohistochemistry showed positivity for TSH (4+) and LH (3+). Antithyroid agents were discontinued and good glycemic control was noted after operation. Conclusion. A biochemical hallmark of TSHoma is an escape of TSH from the feedback loop that is detectable TSH levels in the prescence of increased serum thyroid hormone level. Diagnosis of TSHoma was frequently unrecognized and thus much delayed despite its relatively straightforward. Physician should keep in mind that the importance interpretation of simple laboratory tests to avoid delay diagnosis and unnessary treatments.

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PE-7

PARATHYROID ADENOMA PRESENTED WITH HYPOCALCEMIA IN A PATIENT WITHOUT CHRONIC RENAL INSUFFICIENCY 1

HSUAN-WEI LIN, 1,2CHIN-SUNG KUO

1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan

Elevated serum parathyroid hormone level together with hypocalcemia usually suggests secondary hyperparathyroidism. Parathyroid adenoma commonly co-exists with hypercalcemia, or with normocalcemia in some case reports. We report a case of parathyroid adenoma associated with hypocalcemia in a patient without chronic renal insufficiency. The patient was successfully treated by left inferior parathyroidectomy that was preceded and followed by intensive calcium and vitamin D supplementation. To our knowledge, there is only one previously reported case of parathyroid adenoma associated with hypocalcemia and metabolic bone disease in a patient with chronic kidney disease.

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Abstract PE-8

THYROID MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA IN A 63-YEAR-OLD WOMAN: A CASE REPORT 1

HSIN-WEI WANG, 1EDY KORNELIUS, 1YI-SUN YANG, 1SHIH-CHANG LO, 1CHIENNING HUANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C

Introduction: Primary thyroid lymphoma is rare but still a possible differential diagnosis of thyroid nodule. The major symptom is a rapid growing thyroid nodule. Preexisting autoimmune thyroiditis is a known risk factor. We report a case with thyroid mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) Case: A 63-year-old female suffered from a progressive growing nodule over pre-trachea area in recent 3 months. Physical examination showed a painless, movable, and hard nodule over pre-trachea area. She had history of Hashimoto’s thyroiditis, and thyroid function was euthyroid status under Eltroxin treatment. Thyroid echo showed a 19.0 x 15.9 x 6.6 mm regular hypoechoic nodule over isthmus area. Fine needle aspiration showed atypical cell and polymorphous lymphocytes. Isthmusectomy was arranged by the surgeon and pathology revealed architectural effacement by monocytoid atypical lymphocytes. Mucosa-associated lymphoid tissue lymphoma was diagnosed. Further tumor survey with Positron Emission Tomography showed no residual tumor or distal metastasis. Ann Arbor staging was stage IE (Extranodal). Panendoscopy was arranged which revealed acute gastric ulcer and gastroesophageal reflux disease. Test for Helicobacter pylori infection showed positive. No gastric MALT lymphoma was found. Hematologist was consulted for further treatment, and gastric Helicobacter pylori eradication was suggested followed by chemotherapy or closely monitor.

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PE-9

131I ABLATION THERAPY IN PATIENT WITH THYROID CANCER AND ESRD ON HEMODIALYSIS: CASE REPORT 1

CHIH-JEN WANG, 1SHU-YI WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan, R.O.C

Radioiodine ablation (131I) is primarily administered postoperatively as a ablation or adjuvant treatment after thyroidectomy for well differentiated thyroid cancers. 131I dosage recommendation and benefits of postoperative RAI administration are different according to the three American Thyroid Association (ATA) risk categories (low, low-to-intermediate and high risk). For a patient with a normal renal function, iodine is mainly eliminated by the kidney, and majority of iodine is absorbed by the thyroid gland. Therefore, the administered dosage of 131I and the timing of hemodialysis are critical issues in a patient with end-stage renal disease (ESRD) on hemodialysis. Here we presents a case with thyroid papillary carcinoma and ESRD on hemodialysis, who received approximately 50% of a typical empirical dose of 131I for a patient with ATA low-to-intermediate risk. From the review of previous literatures, few publications have prescribed the recommendations for management of thyroid cancer in patients with ESRD. Therefore, we focused on three important questions in patients with ESRD on hemodialysis, including: (1) recommendation of modified 131I dose; (2) when to perform hemodialysis after the 131I administration in order to maximize treatment benefit while minimizing the risk to the patient and the treating medical personnel; and (3) safety concerns regarding radioiodine activity during hemodialysis. In this paper, we will review previous literatures concerning these critical questions, and we hope to share our management experience and literature review may help other clinical physicians to face the similar clinical scenario in future.

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Abstract PE-10

BILATERAL ADRENAL GLAND HEMORRHAGE: A CASE REPORT AND REVIEW OF THE LITERATURE 1

YUNG-NIEN CHEN, 1CHEN-KAI CHOU, 1JUNG-FU CHEN, 2HAN-MING LAI

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.; 2Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.

Background. Adrenal hemorrhage is an uncommon condition with variable presentation that may lead to acute adrenal crisis, shock and mortality. Methods. We report clinical features and imaging findings of a middle-aged female with acute bilateral adrenal gland hemorrhage. Results.

A 66-year-old woman presented with a 1-week history of epigastric pain. Eosinophilia was noted and computerized tomography of abdomen showed bilateral adrenal hemorrhage and mesenteric vasculitis, suspect autoimmune disease related. The raised titers of anti-beta2 GPI and anti-cardiolipin IgG antibodies were considered to strongly suggest an underlying diagnosis of the antiphospholipid syndrome. Elevated serum IgG4 was also noted. The patient’s symptoms of adrenal failure resolved after administration of intravenous corticosteroids in an appropriate dose and eventually discharged home. Conclusion. Adrenal hemorrhage is a rare condition and may be associated with stress, sepsis and autoimmune diseases. Bilateral adrenal hemorrhage commonly leads to acute adrenal insufficiency, adrenal crisis, and death, unless it is recognized and treated promptly.

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PE-11

DECIPHERING THE REGULATORY CODE OF THE RELATIONSHIP BETWEEN THE CHOLINE TRIMETHYLAMINE LYASE (CUTC) AND CARDIOVASCULAR DISEASES 1

MING-CHAN LEE, 2YEH CHEN, 3SHIH-TING TSENG

1

Department of Nephrology, Da-Chien General Hospital; 2Department of Department of Biotechnology, Hungkuang University; 3Department of Metabolism and Endocrinology, Kuang-Tien General Hospital

Cardiovascular disease (CVD) is composed of numerous heart and vessel problems, especially a process called atherosclerosis. In our dietary intake, like choline, phosphatidylcholine (PC), carnitine, can be converted to trimethylamine (TMA) by some unique gut microbiota. The generation of TMA is followed by the production of trimethylamine N-oxide (TMAO) converted by host flavin-containing monooxygenase 3 (FMO3). Eventually, the elevated TMAO are associated with atherosclerosis and cause the cardiovascular disease. In this project, we had focused on the gut-bacterial enzyme named Choline/TMO-lyase CutC, which is a key enzyme involved in the choline-TMA conversion pathway. To dissect the CutC enzyme, we had designed a series of the in vitro experiments, that is, the expression and purification of the recombinant CutC enzyme. This project will lay a foundation of unraveling the biological function of CutC and the therapeutic design of gut-microbiota-target enzyme based on the structural biology.

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Abstract PE-12

LONG-TERM THERAPEUTIC OUTCOME OF PAPILLARY THYROID CARCINOMA WITH HYPERPARATHYROIDISM: A CASE-CONTROL STUDY 1

CHIH-YIU TSAI, 1SZU-TAH CHEN, 2CHUEN HSUEH, 3YANN-SHENG LIN, 1JEN-DER LIN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.; 2Department of Pathology, Chang Gung Memorial Hospital, Taiwan, R.O.C.; 3Department of General Surgery, Chang Gung Memorial Hospital, Taiwan, R.O.C.

Objective. This study is aimed to evaluate the long term prognosis of papillary thyroid carcinoma patients with hyperparathyroidism following multimodality treatment. Subjects and methods.

We performed a case-control study from a thyroid cancer database of a medical center prospective collected during 1980 to 2013. The study cohort was patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patient matching with propensity score method was conducted for enrollment of control group who had no hyperparathyroidism. The treatment outcomes of cancer were compared. Result. A total of 27 study subjects were identified from 4,062 consecutive thyroid cancer patients. There were 10 primary and 17 renal hyperparathyroidism. We found 3 disease nonremission and 4 mortality events in the study cohort during a mean 7.7 years of follow-up. The risk of non-remission showed no difference compared with control group but the overall mortality was significantly increased (hazard ratio = 4.43 [95% confidence interval = 1.11 – 17.75], P value = 0.035).

All mortality was non-thyroid cancer related, including two cardiovascular events with in-hospital deaths. Conclusion. Papillary thyroid carcinoma patients with hyperparathyroidism were usually diagnosed in early stages with compatible therapeutic outcomes. However, the effect of underlying comorbidity should be carefully evaluated.

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PE-13

CASE REPORT: HYPERTROPHIC OSTEOARTHROPATHY IN 21 YEARS OLD YOUNG MAN 1

WEI-LIN CHEN, 1CHIA-PO FU, 1I-TE LEE

The Division of Endocrinology and Metabolism, Department of Internal medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.

Hypertrophic osteoarthropathy presents either thickened scalp, clubbing digits or both. The primary type is a rare genetic disorder resulted by failure of prostaglandin metabolism. We present a case with incomplete type primary hypertrophic osteoarthropathy.

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Abstract PE-14

ACROMESOMELIC DYSPLASIA MAROTEAUX TYPE WITH VITAMIN D DEFICIENCY -A CASE REPORT 1,3

YU-YI LIN, 1HONG-DA LIN, 1HARN-SHEN CHEN, 2DAU-MING NIU, 3 KUANG-KUO WANG 1

Section of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan; 2Department of Pediatrics, Taipei Veterans General Hospital, Taiwan; 3Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan

Background. Acromesomelic dysplasia Maroteaux type (AMDM) is an extremely rare autosomal recessive osteochondrodysplasia belonging to the group of acromesomelic dysplasia and first described in 1971 by P. Maroteaux. It is caused by mutations in the NPR2 (neuropilin 2) gene located on chromosome 9p21-p12 which encoding the natriuretic peptide receptor B( NPR-B).

NPR-B acts as the transmembrane receptor for cartilage natriuretic peptide (CNP). Both CNP and NPR-B are important for regulation of longitudinal growth. Clinical features are severe dwarfism with height below 120 cm, shortening of middle and distal segment of limbs, dolichocephalic skull with shortness of the trunk, reduced vertebral height without any associated facial or mental abnormalities.

Radiological features showed short broad fingers, shortening of long bones with bowed radius, and vertebral abnormalities. We report laboratory data and imaging findings of a 40-year-old Taiwanese woman with typical acromesomelic dysplasia Maroteaux type. Case presentation. A 40-year old woman visited to our endocrine clinic due to painless goiter for one week. Due to specific general appearance, detail history taking and physical examination were done. Her parents are close relative marriage (consanguinity). Patient was married with delivered one normal appearance child in 2012.

Pre-pregnancy screening of the patient revealed grossly unremarkable uterus, ovaries, and fallopian tubes. Her body height was 123 cm, body weight was 32 kg and BMI was 21.15. General examination revealed short stature with specific fingers pattern. Clear mentality without neurological deficit were found. Thyroid nodule work-up showed cystic fluid only. Endocrine hormonal studies were within normal limits except low vitamin-D level (25-OH Vit-D: 19.99 ng/ml). Bilateral forearm and hands x-rays (Figure:1~2) showed short metacarpal and phalangeal bones, pointing appearance of distal ulna.

Tripple film of spine (Figure:3) showed no significant evidence of scoliosis more than ten degree in Cobb’s angle. Bone mineral density of L-spine (Figure: 4) showed osteopenia (T-score: -1.0~-1.6). She was clinically diagnosed as acromesomelic dysplasia, Maroteaux type (AMDM) due to consanguinity marriage with specific x-rays findings. Conclusion Acromesomelic dysplasia Maroteaux type is a rare, inherited, skeletal disorder that results in a particular form of short stature, acromelia and mesomelia.

World literature described around 40 to 50 cases of AMDM till now. Genetic counseling is of benefit for affected individuals and their families. As genetic evaluation was not possible in all these patients, AMDM was diagnosed on clinical ground.

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PE-15

HUGE PARATHYROID MASS WITH HYPERCALCEMIC CRISIS: A CASE REPORT 1

PAO-LUNG HSIEH, 1WEI-FU HUANG, 1PO-CHENG CHEN, 1KAI-JEN TIEN, 1NAICHENG YEH, 1SHANG-GYU LEE, 1CHWEN-YI YANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

Background: Hypercalcemic crisis represents a life-threatening emergency. The most common cause is hypercalcemia of malignancy. Previous undetected primary hyperparathyroidism, medicationinduced hypercalcemia, and a few rarer causes may result in this endocrine emergency as well. Primary hyperparathyroidism is a disorder of one or more of the parathyroid glands. Mostly caused by solitary parathyroid adenoma (85%). Parathyroid adenocarcinoma is even rare (< 1 %).

Material and Methods: A 47 years old lady went to our rheumatology OPD due to general soreness for 2 months, and lab data showed hypercalcemia (serum Ca 16.2 mg/dL) and high iPTH (1453 pg/mL). After admission to our Meta ward, thyroid echo showed a lobulated heterogeneous hypoechoic mass inferior to left thyroid gland, about 4.6x3.5cm, with esophagus deviation to right side, suspicious of parathyroid origin. Sella MRI revealed a 3 mm pituitary microadenoma. Pancreatitis and peptic ulcer disease were also diagnosed. Serum level of Gastrin, Chromogranin A and calcitonin were checked. For r/o MEN 1, pancreas MRI was performed, but no definite lesion was detected.

We persuaded the patient to check MEN gene, but she refused. Parathyroid scan and bone scan were arranged and it showed bilateral high intake at lower thyroid lesion.

Results: Subtotal parathyroidectomy was performed. Four normal size of parathyroid glands and one huge mass was seen. Left lower parathyroid gland and this huge mass were removed. However, high iPTH and hypercalcemia persisted. Following chest CT showed a suspicious tumor lesion or hematoma at superior mediastinum. Pathology revealed atypical parathyroid cell for that huge mass and normal parathyroid cell for left lower parathyroid gland.

Conclusion: Primary hyperparathyroidism is rarely due to parathyroid adenocarcinoma or MEN. This unusual case showed atypical parathyroid cell and pituitary microadenoma. Moreover, it is unusual that high iPTH and hypercalcemia persisted after Subtotal parathyroidectomy. Further study and management still be needed.

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Abstract PE-16

LITHIUM-INDUCED HYPOTHYROIDISM: A CASE REPORT 1

CHIN-CHOU YANG

1

Tsaotun Psychiatric Center, Ministry of Health and Welfare

Abstract: Lithium is widely used as a mood stabilizer in managing mental illness, mainly mania and bipolar disorder. In this article, we report a 38 years old woman admitted for mania. Lithiuminduced hypothyroidism was found. It is strongly recommended to evaluate thyroid function before starting to treat psychic patients with Lithium. If hypothyroidism develops, treatment should be carried out according to guidelines, and it does not require withdrawal of lithium.

Case report: A 38 years old woman without systemic disease was admitted to our psychiatric ward in May 2016, under the diagnosis of mania disorder. The routine laboratory study revealed normal thyroid function at first. (TSH: 2.56 uIU/ml, FT4: 0.66 ng/dl) Her medication included Carbamazepine, Estazolam, Trihexyphenidyl, Haloperidol, and Lithium. In September 2017, abnormal thyroid function was found. (TSH < 0 uIU/ml, FT4 1.18 ng/dl) On January 2018, we rechecked thyroid function again, together with adrenal function and thyroid antibodies. The data revealed: TSH 17.39 uIU/ml, FT4 0.32 ng/dl, T3 0.77 ng/ml, AM Cortisol 10.19 ug/dl, TSHR Ab 9%, Anti-TPO Ab > 13000 IU/mL. The tentative diagnosis was Lithium-induced hypothyroidism. Levothyroxine was prescribed for hypothyroidism treatment.

Discussion: The thyroid axis is prone to interactions with many drugs, and hypothyroidism is the most common condition of drug-induced thyroid dysfunction (1). Drugs can induce hypothyroidism through different mechanisms, including inhibition of synthesis and/or release of thyroid hormones, inhibition of TSH synthesis, and other immune mechanisms. Lithium is the first-line treatment for bipolar disorder. However, it can cause hypothyroidism by inhibition of thyroid hormone secretion (2,3). Besides, it can also cause goiter and hyperthyroidism (4,5). The prevalence of hypothyroidism induced by Lithium ranged from 6 to 52 percent according to several series (1), and it usually occurs during the first two years of lithium therapy (3). When hypothyroidism develops, it should be treated with thyroxin according to guidelines. Usually, there is no need to discontinue Lithium treatment, especially without consultation with the patient’s psychiatrist first.

References: 1. RIZZO, Leonardo FL; MANA, Daniela L.; SERRA, Héctor A. Drug-induced hypothyroidism.

Medicina (Buenos Aires), 2017, 77.5: 394-404.

2. MCKNIGHT, Rebecca F., et al. Lithium toxicity profile: a systematic review and metaanalysis. The Lancet, 2012, 379.9817: 721-728.

3. LAZARUS, John H. Lithium and thyroid. Best practice & research Clinical endocrinology & metabolism, 2009, 23.6: 723-733.

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4. BARCLAY, Murray L., et al. Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence. Clinical endocrinology, 1994, 40.6: 759-764.

5. MILLER, Karen K.; DANIELS, Gilbert H. Association between lithium use and thyrotoxicosis caused by silent thyroiditis. Clinical endocrinology, 2001, 55.4: 501-508.

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Abstract PE-17

COMPUTER-AIDED DIAGNOSTIC TECHNIQUE IN FDG POSITIVE THYROID NODULE– A CLINICAL EXPERIENCE OF 73 NON-THYROID CANCER PATIENTS 1

YI-HSUAN LIN, 1SZU-TAH CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Aim: The aim of this study was to characterize ultrasonography (US) features by a computeraided diagnosis (CAD) technique together with PET characters of 18-FDG-avid benign thyroid nodules to help clinical decision making.

Patients: From August 2008 to October 2016, a total of 81 incidentally found FDG-avid thyroid nodules were found in 73 non-thyroid cancer patients (32 males and 41 females, aged from 38.7 to 84.6 years) at Chang-Gung memorial hospital (CGMH). Another 38 non-FDG-avid nodules were found in these patients after US examination. Eventually16 of these patient received thyroidectomy.

Diagnosis: US were retrospectively analyzed by expert endocrinologists according to the Thyroid Image Reporting and Data System (TIRADS) and the CAD software (AmCAD-UT; AmCad BioMed, Taiwan), respectively. The CAD parameters include anechoic area, hyper- and hypo- echogenicity, heterogeneity, margin, taller than wide, eccentric area and the lesion size was measured at the greatest dimension of the nodule. The final diagnosis was confirmed by either FNA cytology and/or pathological report. 45 benign, 5 indeterminate and 19 (8 thyroid and 11 metastatic) malignant lesions were reported in 69 FDG avid nodules by FNA or operation. In contrast, 16 benign, 1 indeterminate and 1 thyroid cancer were reported in 18 non-FDG-avid nodules by FNA. Result: No significant difference of lesion size or individual CAD parameters was found between benign, indeterminate and malignant groups in FDG-avid nodules. Linear regression was then applied to correlate the CAD parameter with the standardized uptake value (SUV) in FDG-avid nodules, which showed one-unit elevation of SUV decreased 0.48 units of eccentric area value (p < 0.05). A taller than wide CAD character was found significantly different between thyroid originated cancer and metastatic lesions (0.30 vs 0.16, P < 0.05). In patients with simultaneous FDG-avid and non-avid nodules, a larger size (2.21 vs 1.68, p < 0.05) was found in the FDG-avid nodules without significant difference among CAD parameters and TIRADS score. To determine the cut-off value of the CAD parameters, 0-7 points were given for the sum-up of each parameter positive for malignant tendency.

The best discrimination point for the prediction of malignancy was 1 with a sensitivity of 100% and a specificity of 33.3%. The area under the ROC curve (AUC) was 0.657 with 95% confidence interval (95% CI) within 0.544-0.759; p < 0.05. The AUC increased to 0.728 with 95% CI within 0.618-0.821 and a 0.0705 difference between areas, p < 0.05 when the PET score was combined.

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Conclusion: We concluded that FDG-avid thyroid nodules with irregular shape of solid component and greater than 15% cystic part may represent benign nodules. Moreover, PET improves the diagnosis of thyroid malignancy by AmCAD.

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Abstract PE-18

PARAGANGLIOMA AT CAROTID BIFURCATION PRESENTING AS CAROTID BODY TUMOR, COEXISTENCE WITH PAPILLARY THYROID CARCINOMA: A DIAGNOSIS DILEMMA 1

FAN CHOU, 1CHIH-YUAN WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, ROC.

PURPOSE To establish the difficulty of differentiating the neck mass between carotid body paraganglioma and recurrent papillary thyroid carcinoma.

METHOD We present a case report of a 66-year-old woman with previous history of papillary thyroid carcinoma, presumed a left carotid body tumor, as was expected from clinical and MRI findings.

RESULT Repeated cytology examination showed carcinoma, metastasis. Lab revealed normal thyroid function, low level of thyroglobulin, and the patient had no sign of malignancy. Biopsy examination revealed non-functional paraganglioma at carotid bifurcation.

CONCLUSION Carotid body tumors are rare tumors but highly related with neck paraganglioma, which mostly benign tumor, might related with germline of SDHx, SDHAF2, MAX and TMEM127 mutations. Differential diagnosis is crucial not only for planning surgery, but also for the postoperative treatment. The vascular structure and relationship with the adjacent vascular structures of the tumor should be detected by noninvasive diagnostic methods such as MRI and magnetic resonance angiography. Thus, surgical complications can be significantly reduced. Radiotherapy is recommend for giant and recurrent carotid body paragangliomas, advanced and unresectable, multiple tumors, and with malignant carotid body paragangliomas metastatic to the regional lymph nodes.

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PE-19

GRAVES’ DISEASE COMPLICATED WITH HASHIMOTO ENCEPHALOPATHY: A CASE REPORT AND REVIEW OF LITERATURE 1

SHIH-CHE HUA, 2CHIEN-CHUNG CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.; 2Division of Neurology, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.

Hashimoto encephalopathy (HE) is known as a steroid-responsive encephalopathy associated with high titers of antithyroid antibodies. The prevalence is rare and estimated to be 2.1/100 000 subjects.

HE is predominantly diagnosed in the adult population and the mean age is around fifty. We reported a pediatric case of Graves’ disease complicated with HE. A 15-year-old girl was brought by her parents to visit our endocrine clinic because of weight loss of 8 kg, behavioral changes, confusion, psychosis, and sleep disturbances over 3 weeks. Neurologist was consulted simultaneously and neurologic examinations were normal except confused mental status. Two months ago, she was diagnosed with Graves’ disease in another hospital and treated by methimazole 20mg per day. According to her parents’ statement, her thyrotoxic symptoms and thyroid function tests improved after initial medical treatment. However, her mental status dramatically altered 3 weeks before, associated with weight loss. Lab tests results showed no leukocytosis and thyrotoxicosis with marked high antithyroid antibodies: TSH 0.008 uIU/mL (normal 0.270-4.200), free T4 > 7.77 ng/dL (normal 0.93-1.70), T3 620.3 ng/dL (normal 84.6-201.8), TSH receptor Ab 83% (< 14%), thyroglobulin Ab 3443 IU/mL (< 115), anti-TPO Ab >13000 IU/mL (< 60). Head CT was performed and showed mild brain edema (Fig.1). HE was highly suspected and empirical steroid therapy given with intravenous Dexamethasone 4mg stat followed by daily Dexamethasone 3mg per day orally. The patient’s mental status dramatically improved and returned to the baseline after steroid treatment. After one month of antithyroid and steroid therapy with methimazole 30mg/day and Dexamethasone 3mg/day, her thyroid function much improved (TSH 0.009 uIU/mL, free T4 0.36ng/ dL, T3 620.3 ng/dL) and mental status stayed normal. Follow-up head CT revealed improved brain edema (more clear cortical sulci) (Fig.2).

The diagnosis of HE is based on neuropsychiatric symptoms, increased titers of antithyroid antibodies, and exclusion of other possible diseases. The most important presenting symptom of HE is altered mental status. Cognitive dysfunction, such as memory dysfunction and speech disturbance, is reported in 80% of patients, and behavioral changes are reported in 90%-100% of patients1,2. In most cases of HE, routine blood laboratory tests are normal. Hypothyroidism was observed in 52% of the reported pediatric patients, and 48% were euthyroid3. Comparison with our case, hyperthyroidism with HE is not frequent though with marked high anti-TPO Ab. Almost all reported cases of HE were 146

Abstract responsive to high doses of steroids4,5. It is usually administered by prednisolone at a dose of 1 g/d over 3 to 5 days. Clinical recovery usually occurs in the first 4 to 6 weeks of treatment, with varying treatment durations from 4 months to 10 years6. Plasmapheresis may be considered if the patient does not respond to the conventional treatment, such as steroids. Comparison with our case, she is good responsive to steroid and clinical recovery happened very soon. In the literature, most HE patients have a good prognosis, although there are no data on the long-term outcome of the disorder7.

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PE-20

THYROID CANCER PRESENTED WITH AN INTERRUPTED PERIPHERAL CALCIFICATION IN SONOGRAPHY —A CASE REPORT 1

WEI-HSIN HSU, 1I-MIN PAN, 2SHIH-MING HUANG, 3SHU-LING PENG, 4HAWCHIAO YANG, 5CHIANG-CHIN TSAI 1

Department of Internal Medicine, 4Department of Radiology, 5Department of Surgery, Tainan Sin-Lau Hospital, Tainan, Taiwan; 2Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan, 3 Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan

Peripheral calcification sometimes has been considered as an indicator of a benign nodule. We report a case of thyroid papillary carcinoma presenting with disrupted peripheral calcification in gray-scale sonography. A 39-year-old female complained of dizziness with whirling sensation for 4 months. On physical examination, blood pressure 104/71 mmHg, heart rate 87/min, mild thyroid enlargement. Thyroid function was within normal limits. Thyroid sonogram demonstrated an illdefined hypoechoic nodule with interrupted peripheral calcifications in left lobe, about 2.4cm in size and one tiny right thyroid cyst about 3mm. Fine needle aspiration did not disclose malignant findings.

Total thyroidectomy proved to be a thyroid papillary carcinoma in left lobe.

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Abstract PE-21

A CASE REPORT OF CUSHING DISEASE RELATED MULTI-SYSTEM FAILURE. 1

SHEAU-FANG PAN, 2HARN SHEN CHEN

1

Depeartment of Internal Medicine, Taipei City Hospital: Yang-Ming Branch, Taipei, Taiwan, R.O.C.; 2Section of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C

Cushing’s disease is caused by pituitary corticotropin (ACTH)-secreting tumors which lead to hypercortisolism. Patients present with high serum ACTH, serum cortisol, and urinary cortisol and 17-hydroxycorticosteroid. This patients with Cushing’s disease became immunocompromised and soon developed pneumonia and ARDS, cardiac myopathy with heart failure, GI bleeding, and renal failure.

Patient received ECMO, machine ventilation, CCVH, and later hemodialysis as well as antibiotics, antifugal, inotropic support, and multiple blood transfusion. Patient improved and received endoscopic transsphenoidal surgery successfully.

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PE-22

THE EFFECT OF THYROXINE SUPPRESSION THERAPY ON GOITER SIZE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN CHIUNGYA CHEN, FENG-HSUAN LIU Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

Background: The prevalence of thyroid nodules was high in general population, especially in elderly and women. Suppressive thyroxine treatment in reducing the growth of nodules had been used for a long time but its efficacy and possible bone loss in postmenopausal women were still on debate. The aim of this study is to evaluate the effect of suppressive thyroxine treatment in the clinical management of thyroid nodules and the change of bone mineral density (BMD) in postmenopausal women during treatment. Methods: Ninety-four postmenopausal women diagnosed with nodular goiter or multinodular goiter at the Chang Gung Memorial Hospital (CGMH) between February 2001 and December 2017 were analyzed retrospectively. Forty-five patients receiving suppressive thyroxine treatment were defined as LT-4 group and 49 patients without thyroxine treatment were defined as control group. In LT-4 group, BMD of each subjects in LT-4 group were further measured. Results: The volume of nodules reduced during 2 years follow-up in both LT-4 group and control group, but there’s no significant difference in nodule size between these two groups. In the LT-4 group, the volume of nodule was decreased significantly in the initial 2 years (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, P = 0.033), but there is no difference in the control group (from 3.48 ± 4.36 to 3.09 ± 2.88 mL, P = 0.239). However, when compared to baseline, the volume increased insignificantly later during 7 years follow-up (4.91 ± 5.40 mL, P = 0.711) and 9 years follow-up (6.06 ± 7.03 mL, P = 0.208) in LT4 group. The best cut-off value of nodule volume to be treated is 2.6mL (AUC=0.740, sensitivity: 0.750, specificity:0.733, P = 0.010) and the diminished thyroid volume in 21 patients (84%) was observed in LT-4 group during 2 years follow-up. During the thyroxine suppressive treatment, BMD had no significant change in lumbar spine (from 0.989 ± 0.134 to 0.981 ± 0.135 g/cm2, P=0.460), hip (from 0.806 ± 0.091 to 0.810 ± 0.094 g/cm2, P = 0.474) and femoral neck (from 0.742 ± 0.090 to 0.750 ± 0.083 g/cm2, P = 0.204) in 2 years. Conclusions: The volume of thyroid nodules reduced significantly in initial 2-years of suppressive thyroxine treatment in postmenopausal women and larger nodule (> 2.6 mL) had higher rate for volume reduction. Thyroxine suppressive treatment resulted in minimal effect in bone mineral density. But longer than 2 years of suppressive thyroxine treatment may not be benefit in nodule size control.

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Abstract PE-23

STEMNESS ACTIVATION IN ADRENAL CORTICOMEDULLARY MIXED TUMOR STUDIED BY WHOLE EXOME SEQUENCING 1

HSIN-YING CHIOU, 1HE-JIUN JIANG, 2SHEAU-FANG YANG, 1WEI-WEN HUNG, 1PIJUNG HSIAO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C; 2Department of Pathology, Kaohsiung Medical University, Taiwan, R.O.C

Background: Mixed corticomedullary tumor (MCT) is a single adrenal tumor containing both cortical and medullary cells intermixed throughout the entire neoplasm. It is extremely rare to be regarded as a new disease entity. Genetic mutation for the tumor formation is still unclear.

We ever reported a 32-year-old female patient who has been diagnosed with a huge adrenal MCT. She was clinically manifested with typical Cushing’s syndrome. And mixed cortical adenoma and pheochromocytoma was documented both by biochemical and immunohistochemical evidences. This study aims to elucidate the etiology of MCT through decipher of the genetic mutations. Methods: Genomic DNA was extracted for whole exome sequencing (WES) using the high throughput next generation sequencing performed with Illumina HiSeq system. Before analysis, the tumor tissue was isolated as pheochomocytoma part (PHEO) and adrenal cortical adenoma (ACA) parts by pathologist.

And patient’s blood was referred as a non-tumor control. Identified mutations were further validated

by Sanger sequencing, and the related aberrant pathways were examined by immunohistochemistry.

Results: There were 5,562 and 2,126 variants identified in ACA and PHEO parts respectively. Among these mutations, neither the known gene mutations of ACA (including GNAS,CTNNB1, PRKAR1A, PRKACA, PDE11A, PDE8B), nor that of PHEO (including RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, EGLN1(PHD2), EPAS1(HIF2A), KIF1B, MET, and FH) were identified from this tumor. However, there were 1,559 variants co-existent in both ACA and PHEO parts. For all of the variants, 1,338 variants (85.8%) also occurred in blood sample. For further functional/pathway analysis, these mutated genes were associated with dominant enrichment of cell stemness regulation. The stemness expression, examined by immunohistochemical markers SOX2 and CD44, was significantly present both in ACA and PHEO parts. At the same time, this mixed tumor was also demonstrated with the aberrant MAPK signaling in PHEO part and extracellular matrix (ECM)-receptor interaction/Focal adhesion in ACA part by the pathway analysis from these PHEO/ ACA-specific mutation genes. Discussion and conclusion: From our result, adrenal MCT is actually a diverse disease entity different to pheochromocytoma or adrenal Cushing adenoma. This is the pilot study to provide molecular evidences to explore the etiology of adrenal MCT. From the significant expression of stemness markers in this case, it is speculated that germline mutations in stemness regulation may trigger the first hit for tumor formation. And the aberrant MAPK signaling and ECMreceptor interaction may stimulate further tumor proliferation and adhesion to intermix together.

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PE-24

CLINICAL SIGNIFICANCE OF HEPATIC I-131 UPTAKE IN THYROID CANCER 1

YI YIN LEE, 1SZU TAH CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Objective: The purpose of this retrospective study was to determine the clinical importance of hepatic uptake of radioactive iodine after I131 ablative therapy in patients with thyroid cancer and if there is correlation between hepatic uptake and distant metastasis. Method: A total of five hundreds seventy six I-131 whole body scans performed (223 diagnostic scans and 353 post-therapy scans) on 40 patients with thyroid cancer (35 papillary, 3 follicular, 2 poorly differentiated) found to have once or more incidence of hepatic uptake were reviewed retrospectively from May1997 to Jan 2017 at Chang Gung Memorial Hospital (Taiwan). All patients received I-131 ablation therapy after bilateral total thyroidectomy. Thyroxine were discontinued around four weeks earlier or received thyrogen injection and had elevation of thyroid stimulating hormone level (TSH > 30 IU/ml) before radioactive iodine scan. Local uptake and diagnostic scan (2-10mCi) was performed at 24 hours and within 72 hours, respectively (early scan). The therapeutic scan (30-200 mCi) was performed and measured within 6-12 days (Late scan). Data including age, gender, histopathology and TNM stage were collected and divided into groups with or without distant metastasis. Serum thyroglobulin (Tg), TSH, serum Tg-Ab, serum ALT level and serum AST level were also obtained. Diffuse or focal hepatic uptake was visualized by well-experienced nuclear medicine physician that grading from 0: no uptake; 1: equivocal uptake; 2: faint or mild uptake; 3. Moderate or focal uptake; 4. Intense or diffuse uptake.

For serum TSH, serum Tg, ALT and AST levels, the Mann-Whitney U test was used to measure the statistical significance between distant metastasis group and no distant metastasis group. The Pearson Chi-square test was used to analyze categorical variables. Results: The median age was 43.38 [33.60; 55.75] years and most of patients are females (N = 31; 77.5%). Among seven patients with distant metastasis, two patients showed diffuse hepatic uptake on the early scan. Four patients showed focal hepatic uptake and three patients revealed diffuse hepatic uptake. The serum levels of ALT, AST and serum Tg-Ab showed no significant difference between the two groups. Serum Tg showed higher level in distant metastasis group than no distant metastasis group (18.30 vs 0; p = 0.016). Conclusion: In our study, seven of forty hepatic uptake in I-131 whole body scan were found to have distant metastases.

There was no significant difference of ALT, AST and serum Tg-Ab level between groups with or without distant metastasis group. Serum Tg seemed to be the only marker to predict distant metastasis in patients with hepatic uptake.

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Abstract PE-25

FALSELY HIGH RESULTS IN MULTIPLE HORMONE IMMUNOASSAYS – A CASE REPORT 1

HUI-CHUAN HSU, 2YA-CHIEH FANG, 3CHING-LING LIN, 4YI-HSUAN LI, 5LI-WEI YEH

1

Divison of Endocrinology and Metabolism, Sijhih Cathay General Hospital, Taiwan, R.O.C.; 2Department of Endocrinology, and Radioimmunoassay Laboratory, Cathay General Hospital, Taiwan, R.O.C.; 3Division of Endocrinology and Metabolism, Cathay General Hospital, Taiwan, R.O.C.; 4Department of Laboratory Medicine, Sijhih Cathay General Hospital, Taiwan, R.O.C.; 5Chiu Hospital, Taiwan, R.O.C.

Abstract Objective: Immunoassay methods have been widely used in many important areas of health care for decades. These methods rely on the assay antibody detecting target analyte that could be an inherent drawback. With the advance of immunoassay technique, clinically significant interferences are uncommon. Here we share a case with endogenous antibody interfering with multiple hormone immunoassays. Methods: We present a case clinical history, laboratory data and methods to investigate immunoassay interference.

Results: A 61-year-old woman was referred to our outpatient department for an elevated thyroid-stimulating hormone (TSH) level of > 100 uIU/mL in her health checkup reports. After six months of levothyroxine replacement, TSH level remained high despite her free thyroxine level had reached above normal range. Pituitary image was a negative finding. Multiple hormone levels were unexpectedly high, including prolactin, luteinizing hormone, follicle-stimulating hormone and estradiol. Reanalysis with different platforms yielded discrepant results and was suggestive of immunoassay interference. Further investigation showed that the patient had a high level of rheumatoid factor. Patient sample treatment with heterophilic blocking tube could reduce falsely positive results in the same brand platform as well as the level of rheumatoid factor.

Conclusions: Base on a serial investigation, we believe this case with erroneously high results in many hormone tests caused by endogenous antibody interference. Clinicians need to be aware of them and alter to the mismatch of clinical feature and laboratory data. Early recognition would prevent inappropriate treatment.

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PE-26

CLINICOPATHOLOGICAL FEATURES OF PAPILLARY THYROID CARCINOMA PATIENTS WITH POSITIVE BRAF V600E MUTATION: SINGLE CENTER EXPERIENCE IN TAIWAN 1

HE-JIUN JIANG, 1CHIA-WEI LAI, 1WEI-LUN WEN,

1

NAI-WEI SHEU, 1SHU-HENG HUANG, 1PI-JUNG HSIAO Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 1

Background: BRAF V600E point mutation is the most common genetic event in papillary thyroid carcinoma (PTC) worldwide. Theoretically, it may alter the MAP kinase/ERK signaling pathway to promote cancer cell growth and progression. However, the association between BRAF mutation and clinicopathologic significance of aggressiveness and recurrence remained controversial and was not fully documented in Taiwan population.

Methods: This was a retrospective cohort study to enroll total of 300 PTC patients, mean aged 45.4 (± 12.5) years, from January 1985 to December 2017. All of them were treated by total thyroidectomy and empiric radioiodine therapy and were kept continuous follow-up at our hospital for 40.1 (± 38.2) months. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor or lymph nodes specimens in tissue bank for BRAF mutation identification. The chi-square test was used to compare the significant difference of the clinicopathologic features between groups of V600E mutation and the wild type of BRAF gene.

Results: The frequency of BRAF V600E mutation was 51.7% (155/300) of PTC patients. Patient with BRAF V600E mutation significantly had bigger main tumor size (2.07 ± 1.21 cm vs 1.64± 1.33, p = 0.004 ), significant higher risk of extrathyroid extension (67.1% vs 46.2%, p < 0.001 ), especially gross extrathyroid invasion (9.0% vs 2.8%, p = 0.022), greater risk of harboring lymphovascular invasion ( 39.4% vs 24.1%, p = 0.005) and capsule invasion (29.7% vs 14.5%, p = 0.002 ) versus patients with wild type. Initially, there was no difference of lymph node metastasis (80.0% vs 76.6%, p = 0.469) and distant metastasis (2.6% v.s. 4.1%, p = 0.674) in both groups.

However, the cohort revealed higher tumor recurrence over lymph nodes (27.1% v.s. 16.6%, p = 0.028) and higher I131 accumulated dosage (165.6 ± 90.6 vs 143.8 ± 94.3 mCi) in group of BRAF V600E mutation than wild type group. Within this period, two cases positive of BRAF V600E mutation died but not any mortality in cases of wild type.

Conclusion: BRAF V600E point mutation was identified in more than half of PTC patients in our study. Carriers with BRAF V600E mutation significantly harbored more aggressive pathologic behavior, including extrathyroid extension, lymphovascular and capsule invasion, which could highly implicate the risk of disease recurrence. So, we strongly recommend to screen BRAF V600E mutation for PTC patients to determine proper treatment strategy and work-up for follow.

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Abstract PE-27

METASTATIC POORLY DIFFERENTIATED THYROID CARCINOMA ARISING IN STRUMA OVARII WITH COEXISTENCE OF GRAVES` DISEASE AND MICROPAPILLARY THYROID CARCINOMA 1

YA-MEI HSIEH, 1I-TEE LEE, 1YU-HSUAN LI

1

Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taiwan, R.O.C

Background: Poorly differentiated thyroid cancer originated from struma ovarii was rare cancer.

There was limited evidence and treatment option in this group Case presentation: A 23 year old woman presented with urinary frequency and low abdominal mass. She underwent left side ovarian cystectomy. The cystic mass showed evidence of struma ovarii with poor differentiated transformation.

There was no evidence of residual tumor or metastasis after patient received LSO+LN+omentum and Tc 99m scan. There was no evidence of recurrent tumor in the following two years. However, patient was bothered by anterior chest pain. Chest x-ray and CT disclosed multiple lung nodules and mediastinum lymphadenopathy. Metastasis from malignant struma ovarii was suspected according to cytology from sternal bone and histology of lung nodule. Micro-papillary carcinoma was found accidentally after total thyroidectomy. whole body scan showed partially uptake after 150mCi of radioactive iodine. Patient was under target therapy. Conclusions: Due to relatively higher possibility of metastasis and worse prognosis, Treatment protocol and follow up program should be build up in this group.

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PE-28

SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR PREDICTING REDUCTION IN PULSE PRESSURE AFTER A ONE-HOUR REST IN NURSES WORKING NIGHT SHIFTS 1

I-TE LEE, 1WAYNE HUEY-HERNG SHEU

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital

Night shift work is associated with cardiovascular disease and central nervous system disorders in female nurses. Brain-derived neurotrophic factor (BDNF) exerts protective effects on neural and endothelial functions. This study examined the association between serum BDNF levels and pulse pressure after rest in female nurses working night shifts. In this study, blood samples were collected for BDNF measurement after a night shift when nurses had been working night shifts for three continuous weeks. Blood pressure was assessed before and after a one-hour morning rest within a week of resuming the night shift after one month without any night shift work. The pulse pressure of nurses (n = 48, age 29 ± 5 years) was significantly reduced (from 43 ± 7 to 41 ± 6 mmHg, P = 0.003) after rest, and serum BDNF were significantly and inversely correlated with pulse pressure changes (r = -0.435, P = 0.002). Higher serum BDNF was an independent factor for greater reduction in pulse pressure (95%CI = -0.609 ‒ -0.174, P = 0.001). Using a receiver operating characteristic curve analysis, serum BDNF > 20.6 ng/mL predicted a pulse pressure reduction after a one-hour rest (sensitivity 66.7%, specificity 77.8%). In conclusion, higher serum BDNF predicted greater recovery of pulse pressure after a one-hour rest in female nurses after night shift work.

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Abstract PE-29

HEPATOTOXICITY OF PROPYLTHIOURACIL (PTU) IN A BOY WITH GRAVES DISEASE 1,2,3,4,5

YANN-JINN LEE, 1,4,6WEI-HSIN TING, 1,4,6CHI-YU HUANG, 7WAI-TAO CHAN, 1 YA-TING CHIANG 1

Department of Pediatric Endocrinology,MacKay Children’s Hospital; 2Department of Medical Research,MacKay Memorial Hospital Tamsui District; 3Department of Pediatrics,School of Medicine,College of Medicine,Taipei Medical University; 4Department of Medicine,Mackay Medical College; 5Institute of Biomedical Sciences, Mackay Medical College; 6MacKay Junior College of Medicine,Nursingand Management; 7Department of Pediatric Gastroenterology,MacKay Children’s Hospital

Thionamides including propylthiouracil (PTU), methimazole, and carbimazole are used to treat hyperthyroidism. The side effects include skin rash, granulocytopenia, abnormal liver function, and systemic vasculitis. PTU hepatotoxicity appears more often in children than adults. Therefore Nelson Textbook of Pediatrics recommends that PTU should not be used in children since 2011. However the caveat has not been noticed by all doctors. Children with hyperthyroidism are still exposed to the danger. We reported a boy with Graves disease treated with PTU had abnormal liver functionin about 2 months.

Patient report A 7 7/12-year-old boy had a goiter and excessive appetite, heat intolerance, palpitation, and irritability. He was brought to a local hospital. His free T4 was 7.77 (ref 0.89-1.79) ng/dl and ALT was 53 (ref 12-27 IU/l). PTU (50 mg) twice daily was prescribed. His thyrotoxicosis improved and PTU was decreased to once daily 10 days later. A follow-up Free T4 was 1.91 ng/dl and TSH 0.01 µIU/ml at the 55th day of PTU treatment. At the 62nd day, he complained of fatigability, weakness, and anorexia.

His ALT was 713 IU/Land AST499 (21-39) IU/L.PTUwas discontinued. Workups on infectious hepatitis or autoimmune hepatitis were negative. A follow-up ALT was 340 IU/Land AST140IU/Lbut T4 was 24.9 (ref 4.5-12.5) µg/dland T3 651 (ref 100-190) ng/dl 7 days later. He became severely thyrotoxic. Therefore carbimazole 0.5 tablet daily was started and then increased to 1 tablet daily in a day because free T4 was 7.76 ng/dl. His free T4 was 2.76 ng/dl, TSH < 0.03 µIU/ml, ALT 64 IU/l, and AST 50 IU/l in another 11 days. He was active with good appetite. His thyroid was 5 x 2 x 1 cm each side. His anti-TPO Ab was 727.8, anti-Thyroglobulin Ab 223 and antiTSH receptor Ab 68.85%.

Conclusion PTU was hepatotoxic in a boy. The boy's liver gradually recovered afterthe discontinuation of PTU. PTUmust be avoided in children.

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PD-1

MATERNAL AND FETAL OUTCOMES OF PREGNANT WOMEN WITH TYPE 1 DIABETES, A NATIONAL POPULATION STUDY 1

SHU-FU LIN, 2CHANG-FU KUO, 3MENG-JIUN CHIOU, 4SHANG-HUNG CHANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 2Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Office for Big Data Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan;4 Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Purpose: Pregnancy in women with type 1 diabetes is associated with poor maternal and neonatal outcomes. However, the risk of these outcomes has never been evaluated in an Asian national population. In this work, we report the maternal and fetal outcomes of pregnant women with type 1 diabetes in Taiwan.

Experimental Design and Results: A total of 2,350,339 pregnancy records created between 2001 and 2012 were obtained from the National Health Insurance database and analyzed. Here, 630 pregnancy records were identified in women having type 1 diabetes. Compared with pregnant women without type 1 diabetes, pregnant women with the disease showed increased risk of multiple adverse outcomes, including preeclampsia, eclampsia, cesarean delivery, adult respiratory distress syndrome, pulmonary edema, sepsis, chorioamnionitis, pregnancy-related hypertension, puerperal cerebrovascular disorders, acute renal failure, and shock. Fetuses of type 1 diabetic mothers were at increased risk of stillbirth, premature birth, large for gestational age, low birth weight, and low Apgar score. Of the studied endpoints, only preeclampsia showed an improvement in the late period (2011–2012) when compared with the early period (2001–2010).

Conclusion: These findings reveal that pregnant women with type 1 diabetes are at significantly increased risk of developing many adverse maternal and fetal outcomes. Therefore, pregnancy outcomes in women with type 1 diabetes should be improved.

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Abstract PD-2

TPL2 (THERAPEUTIC TARGETING TUMOR PROGRESSION LOCUS-2) / ATF4 (ACTIVATING TRANSCRIPTION FACTOR-4) / SDF1Α (CHEMOKINE STROMAL CELL-DERIVED FACTOR-Α) AXIS SUPPRESSES DIABETIC RETINOPATHY 1

DE-WEI LAI, 2KENG-HUNG LIN, 3WAYNE HUEY-HERNG SHEU, 1,4MEEI-LING SHEU

1

Institute of Biomedical Sciences, National Chung Hsing University, Taiwan; 2 Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan; 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan Rationale: Diabetic retinopathy is characterized by vasopermeability, vascular leakage,

inflammation, blood–retinal barrier breakdown, capillary degeneration, and neovascularization.

However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. Objective: TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of Nε(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples.

Methods and Results: Serum Nε-(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy.

Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between Nε-(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell–derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4).

Conclusions: This study demonstrates that inhibiting the Nε-(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus–mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema. ( Circ Res. 2017;121:e37-e52. DOI: 10.1161/ CIRCRESAHA.117.311066.)

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PD-3

HIGH GLUCOSE VARIABILITY INCREASES RE-ADMISSION RATES WITHIN 30 DAYS OF DISCHARGE IN DEPARTMENT OF SURGERY CHING JUNG HSIEH Department of Internal Medicine, Paochien Hospital, Ping Tung, Taiwan, R.O.C.

Objectives: Glucose variability is common among hospitalized patients with type 2 diabetes mellitus (DM). We investigated to assess the variability of glucosein patient with type 2 DMaccounts for in-hospital readmission rates in department of surgery.

Methods: We retrospectively analyzed 196 patients with type 2 DM, who was admitted to our hospital for surgical interventions and re-admitted for the same disease (including wound infection) within 30days since January 2007 to December 2016. We also enrolled 610age and sex matched patients with type 2 DM, who received the same types of surgery at the same year as control. Outcome measure from electronic medical record included average and standard deviation (SD) of blood glucose during admission,glycated hemoglobin (HbA1c) within 1 month before and after admission, length of stay (LOS), medication for DM and co-morbidity Results: Patients who had re-admission within 30 days of admission had higher SD of blood glucose levels than control ( 84.7 ± 53.5 mg/dL vs. 46.2 ± 42.8 mg/dL, p < 0.001) but not average of blood glucose levels (165.7 ± 27.5 mg/dL vs. 158.3 ± 27.2 mg/dL, p < 0.088). Comparing to control group, the study group also had higher HbA1c ( 8.4 ± 1.3% vs. 7.7 ± 1.1%, p < 0.015). There were no group differences in body weight, blood pressure, lipid profile, LOS, medication and co-morbidity. SD of blood glucose was highly correlated with average blood glucose levels and HbA1cs (r = 0.350; 3.48 respectively, all p < 0.001).The independent predictors ofSD of blood glucose levels during admission and recent HbA1c levels.

Conclusion: Decreasing glucose variability during admission and well blood glucose control before surgery are important for patients with type 2 DM to decreasing re-admission rates.

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Abstract PD-4

EFFECT OF GLP-1 RECEPTOR AGONIST ON PATIENTS WITH TYPE 2 DIABETES IN REAL PRACTICE: EXPERIENCE FROM A REGIONAL HOSPITAL WEI KYANT WANG, CHING-CHIEH SU 1

Internal medicine, Cardinal Tien hospital; 2 Division of endocrinology and metabolism, internal medicine, Cardinal hospital. School of medicine and Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University and

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) is a new injectable antidiabetic medicine. It can lower blood glucose and also result in a neutral or lowered body weight.

However, the interaction of changes in blood glucose and body weight is not clear. Method: This study is a retrospective chart review study. Patients with type 2 diabetes who initiated liraglutide therapy from 1, Sep. 2016 to 30 Nov. 2016 were enrolled. We assessed the change in blood glucose and body weight after liraglutide treatment. Result: The study found that most patients had lower A1C and body weight simultaneously but no relationship between body weight and blood glucose change was found. Univariate correlations revealed baseline A1C was negatively correlated to the change of A1C. Age, gender, duration of diabetes, numbers of oral antidiabetic drugs, baseline body weight and BMI are not correlated to change of A1C. In terms of the change of body weight, younger patients lost more body weight. Numbers of antidiabetic drugs was borderline correlated to body weight change.

In multivariable linear regression models,varibles such as male, diabetes duration, and baseline A1C are all positively correlated and numbers of antidiabetic drugs is negatively correlated to the change of A1C. Age is positively correlated and the number of antidiabetic drugs is negatively correlated to body weight change. As a conclusion, we found that liraglutide could decrease body weight and blood glucose. However, there is no relationship between the glucose reduction and body weight lowering effects. In respect of glucose reduction, male patients with longer diabetes durations, using less oral antidiabetic drugs or higher baseline A1C are good candidates for liraglutide treatment. In respect of body weight reduction, younger patients with less antidiabetic drugs are less likely to lose their body weight.

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PD-5

EMPAGLIFLOZIN REPLACEMENT FOR DIPEPTIDYL PEPTIDASE-4 INHIBITORS IMPROVES GLYCATED HEMOGLOBIN IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES CHUNG-HUEI HUANG, YU-YAO HUANG, BREND RAY-SEA HSU Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

Aims/Introduction: To evaluate the efficacy of empagliflozin replacement for dipeptidyl peptidase-4 inhibitors (DPP4is) in patients with poorly controlled type 2 diabetes.

Methods: This study retrospectively reviewed the data of 197 patients with type 2 diabetes. Their DPP4is were switched to Empagliflozin. Twenty-four patients with upper-titrated other anti-diabetic agents were excluded. Data of the remaining 173 patients with no change of other anti-diabetic agents for 6 months were collected. The body weight (BW) and glycated hemoglobin (HbA1c) values at baseline, and 3 and 6 months after the switch were analyzed.

Results: Sixty-six percent of patients had benefit of glucose-lowering following the switch (9.2% to 8.1% at 3 months and to 7.9% at 6 months, both p < 0.001). The baseline HbA1c level is the only factor that predicts the responsiveness. Negative correlations were found between baseline HbA1c and delta HbA1c after the switch (3 months: ρ = -0.512, p < 0.001; 6 months: ρ = -0.637, p < 0.001).

When baseline HbA1c values were equally sub-grouped into tertiles, glucose-lowering at both 3 and 6 months were found in patients of the second and third tertiles, but not in the first tertile (the lowest HbA1c tertile). A cutoff value of baseline HbA1c 8.4% showed benefit of the switch therapy (74.6% sensitivity and 67.8% specificity). The BW of the patients in all tertiles decreased significantly after the switch.

Conclusions: Empagliflozin replacement for DPP4is showed additional glucose-lowering effects for patients with higher baseline HbA1c and weight reduction effects regardless of baseline HbA1c.

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Abstract PD-6

ASSOCIATION BETWEEN SERUM BILIRUBIN LEVELS AND PROGRESSION OF ALBUMINURIA IN TAIWANESE WITH TYPE 2 DIABETES MELLITUS 1

WAI KIN CHAN, 1SUNG-SHENG TSAI, 1YAN-RONG LI, 1WEI-YU CHOU, 2HSIAOLIEN CHEN, 1SZU-TAH CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan City, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of internal medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Ilan county, Taiwan

Background To investigate the association between serum bilirubin levels and the progression of albuminuria in type 2 diabetic Taiwanese. Methods Longitudinal data from January 2001 to June 2015 were retrospectively reviewed from Chang Gung Memorial Hospital (CGMH). A total of 2788 type 2 diabetic patients with normal total serum bilirubin (BIL) levels were divided into four groups according to BIL quartiles, with the highest BIL in the fourth quartile. The trend and progression of urinary albumin/creatinine ratio (UACR), as well as other laboratory measurements, were compared among the four groups. The cumulative incidence and Cox proportional hazard model analysis were used to examine the relationship between BIL and the risk of albuminuria progression (AUPr), i.e., progression of the stage and/or persistent macroalbuminuria. Results The mean duration of followup was 1.5 years (± 1.37 years). The mean patient age, glycosylated hemoglobin level, and duration of diabetes were 62.52 years, 7.89%, and 3.98 years, respectively. A significant correlation was observed between BIL and both the UACR at baseline (P < 0.001) and the cumulative incidence of AUPr (log– rank test, P = 0.022). In hazard ratio (HR) analysis, patients in the fourth BIL quartile were shown to have the lowest HR among the four groups (adjusted HR = 0.69; 95% CI = 0.53–0.88, P < 0.05).

Conclusions Higher serum BIL levels are associated with a lower risk of albuminuria progression in type 2 diabetes patients in Taiwan.

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PD-7

A CASE REPORT OF ACUTE PANCREATITIS RELATED TO GLP-1 RECEPTOR AGONIST LI JUI-HSIANG, LO SU-HUEY Division of Endocrinology and Metabolism, Department of Internal Medicine Tao-Yuan General Hospital,

Introduction In animal experiment studies, pancreas related to acute or chronic disease was described as sideeffect of GLP-1 receptor agonist. Clinical studies failed to demonstrated a correlation in humans. But we reported a case with pancreatitis history related to hypertriglyceridemia recurred after liraglutide therapy for 3 months.

Case report A 33 year-old male had diabetes for 2 years and acute pancreatitis history due to hyperlipidemia.

Chronic treatment was conducted with novomix 52u bid for diabetes, Sevikar 1# PO BID for hypertension and vytorin 1#qd+fenofibrate 1# qd for hypertriglycemia. The GLP-1 receptor agonist, liraglutide 1.8mg was started 3 months prior to presentation.

This time, he suffered from severe left abdomen and flank pain for one day with vomiting and nausea. He visited our ER for help. Biological exams showed high lipase level 459 U/L-normal range<60u/L), high amylasemia (220U/L, normal range < 100u/), Lactic acid 2.8 mmol/L, elevation creatinine ratio 1.4 mg/dl, CRP 0.124mg/dl , normal hemoglobin level(13.0mg/dl), leukocytosis WBC=12990/ul without left shift and a total Ca level of 8.4mg/dl. Also glycemia was high 200mg/ dl. Ultrasonography scan showed heterogenous echotexture of pancreas, no gallbladder stone or intra/ extrahepatic biliary ducts dilatation and fatty liver. The case was interpreted as acute pancreatitis.

The other laboratory finding was total cholesterol 121 mg/dl, triglyceride=356 mg/dl, LDL=74mg/dl, LDL=136/mg/dl. HbA1c=10.2%. After the exclusion of all other possible causes for acute pancreatitis, the pathology was related to liraglutide treatment. The treatment was interrupted.

Discussion The exact mechanism for this potential adverse effect is not clear; it may be related to the development of antibodies. Liraglutide treatment was studied by pharmaceuticals companies and only 8 cases of acute pancreatitis (all as mild forms) in over 6000 patients treated were reported. A clear causal relationship is difficult to establish. Clinicians should use liraglutide cautiously in patients with history of pancreatitis particularly with disease of hypertriglycemia, alcohol use or cholelithiasis. If pancreatitis is confirmed, liraglutide should be discontinued.

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Abstract PD-8

A CASE OF KLEBSIELLA PNEUMONIA LIVER ABSCESS WITH MULTIPLE SEPTIC METASTATIC INFECTIONS LI JUI-HSIANG, LO SU-HUEY Division of Endocrinology and Metabolism, Department of Internal Medicine Tao-Yuan General Hospital

Introduction Liver abscess is highly prevalent among diabetic patients. In this report, we described a rare case of klebsiella pneumonia liver abscess with multiple metastatic infections to perinephric abscess, perirectal abscess, prostate abscess, posterior pelvic cavity and presacral space.

Case report A 52-year-old male admitted to the emergency room for acute conscious change with irritable behavior. On examination, no significant weakness or numbness was found on neurologic examination. Finger sugar showed Hi. Laboratory analyses produced the following results: sugar = 1675 mg/dl, BUN = 38 mg/dl, Cr = 1.9 mg/dl, AST/ALT = 54/60 IU/L, Na = 109 mg/dl, K = 3.6mg/ dl, Osmolarity = 343 mosm/L,PCT = 11.74 ng/ml, WBC = 28550 /mm3, seg = 92.3%, band = 3.9%, Hb = 10.7g/dl. Therefore, Under the impression of 1.HHS, 2.AKI, 3.Sepsis. He was admitted to our ICU for further evaluation and treatment. The patient was treated with third-generation antibiotics (ceftriaxone) and IV insulin. Abdominal echo revealed cirrhosis of the liver, hepatic tumor suspected abscess. Abdominal CT showed a 2.6 cm lobulated cystic lesion at S7 of liver, favor liver abscess, left perirectal abscess and prostate abscess formation, bilateral acute pyelonephritis, suspected perinephric abscess. The cultured blood and urine were positive for klebsiella pneumonia sensitive to cefazolin and ampicillin. Repeated abdominal CT still showed bilateral sides abscess formation of posterior pelvic cavity and presacral space, hepatic abscess Due to his condition not improving, the patient left the hospital seeking second opinion to Linkou Chang Gung Memory Hospital. Discussion: In patients with diabetes, liver abscess caused by Klebsiella pnuemonia is a known risk factor for embolic complications such as endophamitis, renal abscess, septic pulmonary emboli, chest wall abscess and meningitis. The pathogenic mechanism of primary Klebsiella pneumoniae liver abscess complicated with metastatic infection remains unclear. Fang et al. reported that mag A is an important virulence gene in invasive Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. Physicians should be aware of Klebsiella pneumonia liver abscess and should identify early signs of septic embolic because on the time management remains critical for a good outcome.

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PD-9

ELEVATED SERUM CYTOKERATIN-18 LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE YU-HUNG CHANG, 2HSIEN-CHANG LIN, 1DER-WEI HWU, 1DAO-MING CHANG, 1 KUN-CHEN LIN, 1YAU-JIUNN LEE 1

1

Lee’s Endocrinology Clinic, 2LiTzung Biotechnology, Inc

Background: Cytokeratin-18 (CK-18) is a caspase-cleaved fragment released by injured hepatocytes, and serum levels of CK-18 were believed to be a marker of hepatic cell damage such as inflammation. Patients with type 2 diabetes (T2DM) were well known to have a high prevalence of the fatty liver condition. However, rare studies had been reported the serum CK-18 level in patients with T2DM and investigated the association between the levels with metabolic biomarkers.

Material and Methods: Healthy participants and T2DM patients who followed in the specialized diabetes polyclinic were enrolled. Physical and metabolic factors were collected, and NAFLD was screened by abdominal ultrasound and fatty liver index. Cytokeratin 18 level was detected by commercially available immunoassay (M30 and M65 ELISA kit, Previa AB, Sweden).

Results: There were 22.8% (29/127) and 35.9% (42/117) participants were diagnosed with NAFLD in the non-DM group and T2DM group, respectively. Both serum levels of CK-18 M30 and CK-18 M65 were significantly higher in patients with T2DM as compared with those of the non-DM group. Patients with non-alcoholic fatty liver disease (NAFLD) had higher serum CK-18 M30 level whatever with T2DM (205.8 ± 135.1 vs. 108.4 ± 66.19 U/L; P < 0.001) or without (177.69 ± 70.53 vs.

87.07 ± 34.57 U/L; P < 0.001). Similarly, serum CK-18 M65 was also higher in patients with NAFLD in the T2DM group (513.9 ± 271.2 vs. 285.4 ± 115.3 U/L; P < 0.001) and in the non-DM group (353.5 ± 162.4 vs. 248.51 ± 111.3 U/L; P < 0.001). Multi-variate regression analyses demonstrated that fasting plasma glucose was independently and significantly associated with CK-18 M30 (β coefficient: 0.002; P = 0.011)) and CK-18 M65 (β coefficient: 0.003; P < 0.001). These results suggested that CK-18 level was closely connected with diabetes mellitus.

Conclusions: Independent of NAFLD, our result suggests that CK-18 level was closely associated with the hyperglycemic milieu. The association between serum CK-18 and T2DM may worth for further investigation.

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Abstract PD-10

THE EARLY CHANGES IN AXONAL NEUROPHYSIOLOGY OF AXON IN PRE-DIABETES 1

NGUYEN THI THU TRANG, 4,5TING-I LEE, 2TSUI-SAN CHANG, 2,3JIA-YING SUNG

1

International Master Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 2Department of Neurology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C.; 3 Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 4Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C.; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taiwan, R.O.C

Introduction The sensory neuropathy in diabetes patients has been reported in previous studies.

Sometimes the sensory symptoms have complained at the beginning of diagnosis of diabetes. The possible pathogenesis of neuropathy might start since hyperglycemia stage. Therefore it is supposed that the nerve axonal dysfunction in the pre-diabetes stages. Methodology 95 subjects were enrolled in this study; 72 subjects are pre-diabetic patients with/without neurological symptom and 23 are healthy subjects. All subjects received blood test, standard neurological examination and neuropathy scorereduced (TNSr), nerve conduction study (NCS) and sensory nerve excitability testing (NET). All subjects have their blood test checked one year later to make sure that the blood sugar is persistently higher than normal or not. We excluded the blood sugar is lower Results In compared to healthy control (HCs) cohort, pre-diabetes group had higher fasting glucose (P0.05). Conclusion These results revealed that the electrophysiological changes in peripheral sensory nerves might occur prior to diagnosis of diabetes. According to NET, the changes of superexcitability indices indicated the dysfunction of fast potassium channels which contribute to the stable of membrane potential in the paranodal region of sensory nerve axons. Our results also suggest that the possible pathogenesis in prediabetes might start from the paranodal, which might due to the pumping dysfunction.

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PD-11

PROTECTIVE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKERS ON DIABETIC NEPHROPATHY 1

WU MING-HSIEN, 1CHEN SZU-TAH, 2,3LIN CHIA-NI, 3,4,5CHIU DANIEL TSUN-YEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 2Department of Laboratory Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan, Taiwan; 3Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 4Healthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan; 5Department of Pediatric Hematology/ Oncology, Chang Gung Memorial Hospital, Lin-Kou, Taiwan

Objectives: Diabetic nephropathy (DN) is diagnosed on the presence of micro- or macroalbuminuria (mau or MAU) with or without deteriorated eGFR. Through direct or indirect mechanisms, the renin-angiotensin-aldosterone system plays critical roles in renal disease progression.

Aside from their anti-hypertensive effect, a group of angiotensin receptor blockers (ARB) has been proposed to have reno-protective effect, we thus attempted to determine the effect of ARB on the progression of MAU and eGFR in DN. Patients and Methods: We performed a prospective analysis in 46 type 2 diabetic patients (aged 41-75 y/o) with at least stage 3 CKD (eGFR< 60 ml/min/1.73 m2). In patients with newly diagnosed or pre-existed DN, ARB was prescribed or re-prescribed after a drug holiday for 2-4 weeks with careful adjustment for their blood pressure control. Blood and urinary biomarkers including Cr, eGFR, UACR, HbA1c and lipid profile were recorded before and 1-3 months after ARB treatment.

Results: ARB treatment significantly decreased UACR from 1157.4 ± 1565.0 mg/g (471.0, [159.0, 1864.0], median, [Q1, Q3]) to 1105.1 ± 1518.5 mg/g (328.0, [89.5, 1762.5]) (p = 0.001), especially in patients with MAU (MAU 1844.9 vs 1099.6 mg/L, p = 0.004; mau 184.9 vs 139.7 mg/ L, p = 0.123). Meanwhile, patients with better blood sugar control (HbA1c < 8.0) showed lower MAU; ARB treatment significantly improved UACR in this group but not in the poor controlled group (UACR 1801.3 vs 1683.6, p = 0.128 in HbA1c ≥ 8.0, UACR 795.9 vs 756.3, p = 0.016 in HbA1c < 8.0). LDL level also showed significant improvement (118.2 ± 31.1 vs 104.4±26.4 mg/dl, p = 0.020) after ARB treatment, especially in better sugar controlled group but was not associated with poor controlled group or status of UACR (HbA1c ≥ 8, LDL 131 vs 112, p = 0.293, HbA1c < 8, LDL 114.7 vs 99.7, p = 0.037; mau 94.2 vs 115, p = 0.432, MAU 114.2 vs 98.3, p = 0.056). None of the serum Cr, eGFR, HbA1c, HDL, triglyceride and blood pressure showed significant difference before and after ARB treatment.

Conclusion: ARB remarkably reduces macroalbuminuria and LDL cholesterol, which may reflect a proportional reno-protective effect. Although Cr and eGFR was not changed in this short-term study, the long-term effect of ARB on renal perfusion requires further study.

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Abstract PD-12

FACTITIOUS HYPOGLYCEMIA IN TYPE 2 DIABETES PATIENT-A CASE REPORT 1,2

YU-YI LIN, 1YI-CHUN LIN

1

Section of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan; 2Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan

Hypoglycemia is one of the major and dangerous complication of diabetes mellitus (DM) which may lead to permanent brain damage. There are numerous causes of hypoglycemia in DM patients including poor drugs and dietary compliance, organic causes (autonomic neuropathy, malabsorption, primary adrenal failure, hypopituitarism, gluten-sensitive enteropathy, Addison’s disease) and psychological issues (depression, malingering, factitious disorders). Levels of plasma insulin and c-peptide in the occurrence of hypoglycemia are essential for differential diagnosis.

Factitious hypoglycemia, although difficult to document and only few case series were reported in the literature, is more common in patients with DM than normal population, which occurs secondary to the surreptitious use of insulin or insulin secretagogues (sulfonylureas, meglitinides). It is most common among young women or medical auxiliary and typically associated with a higher incidence of suicide, depression, and personality disorders. Clinical and biochemical findings are similar to those of insulinoma. High plasma insulin with suppressed plasma c-peptide and proinsulin concentrations indicates factitious hypoglycemia due to exogenous insulin injection. Prompt and accurate diagnosis is important to avoid severe hypoglycemic complications, unnecessary multiple extensive and expensive investigations, and surgical intervention for insulinoma. Psychotherapy is the cornerstone once confirmed diagnosis. Here we reported a case of insulin-induced factitious hypoglycemia in a chronic type 2 diabetes mellitus female patient who was initially misdiagnosed as dumping syndrome after subtotal gastrectomy.

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PD-13

A CASE REPORT OF IMMUNE CHECK-POINT INHIBITOR INDUCED AUTOIMMUNE DIABETES MELLITUS 1

YU-PING HUANG, 2SHANG-YIN WU, 1HORNG-YIH OU

1

Division of Endocrinology and Metabolism, 2Division of Oncology and Hematology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

Immunotherapy is effective in multiple malignancies refractory to standard chemotherapies.

With the increasing use of immunotherapy, more and more autoimmune side effects are noted. Here, we describe a case with metastatic lung cancer who developed autoimmune diabetes after an immune checkpoint inhibitor, nivolumab, treatment. This patient is a 67-year-old woman with metastatic non-small cell lung cancer treated with nivolumab as the third line setting after disease progression despite a standard chemotherapy. She had no personal or family history of diabetes. Three weeks after receiving two doses of nivolumab, she developed diabetic ketoacidosis with hyperosmolality, complicated with altered mental status. Autoimmune diabetes was diagnosed on the basis of undetected C-peptide levels (C-peptide New onset autoimmune diabetes mellitus associated with immune checkpoint inhibitor treatment is extremely rare, occurring in less than 1% of patients. Time from drug administration to diabetes onset spanned 1 week to 12 months. The autoimmune diabetes mellitus is caused by destruction of pancreatic beta cells by autoreactive T-cells. Most patients exhibited inappropriately low or undetectable C-peptide. Current management includes traditional treatment strategies for diabetes ketoacidosis. Almost all of the patients remained insulin-dependent for glucose control. With the increasing use of immune checkpoint inhibitors, the incidence of autoimmune side effects associated with these agents is expected to rise. New onset autoimmune diabetes mellitus associated with nivolumab is rare but critical. Early recognition is important to prevent serious morbidity and mortality.

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Abstract PD-14

HISTONE DEACETYLASE INHIBITION OF CARDIAC AUTOPHAGY IN RATS ON A HIGH-FAT DIET WITH LOW DOSE STREPTOZOTOCININDUCED TYPE 2 DIABETES MELLITUS 1,2

TING‑I LEE, 3YAO‑CHANG CHEN, 2,4TING‑WEI LEE, 4,5CHENG‑CHIH CHUNG, 6 SHIN‑YI TSAO, 4,7YU‑HSUN KAO 1

Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taiwan, R.O.C.; 3Department of Biomedical Engineering, National Defense Medical Center, Taiwan, R.O.C.; 4 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C.; 5 Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taiwan, R.O.C.; 6 Division of Endocrinology and Metabolism, Department of Internal Medicine, Sijhih Cathay General Hospital, Taiwan, R.O.C.; 7Department of Medical Education and Research, Wan Fang Hospital, Taiwan, R.O.C.

Objective: Autophagy serves a role in preserving cellular homeostasis. Diabetes mellitus (DM) impairs cardiac autophagy and is associated with an accumulation of cytotoxic proteins that may provoke apoptosis and damage cardiomyocytes. Histone deacetylase (HDAC) inhibitors attenuate cardiac fibrosis and inflammation, and improve cardiomyopathy resulting from DM. However, the effect of HDAC inhibition on autophagy in DM cardiomyopathy has not been investigated.

The purpose of the present study was to evaluate whether histone deacetylase (HDAC) inhibition modulates cardiac autophagy and to investigate the potential mechanisms in type 2 DM (T2DM) hearts. Methods: Electrocardiography was used to evaluate cardiac function and western blotting was used to evaluate protein expression in autophagy, the serine/threonine protein kinase mTOR (mTOR) signaling pathway, poly adenosine diphosphate ribose polymerase 1 (PARP1), insulin signaling, advanced glycosylation end product-specific receptor (RAGE), and proinflammatory cytokines in control rats and in rats treated with a high-fat diet (60% fat) and low-dose streptozotocin (35 mg/ kg) in order to induce T2DM, with or without an HDAC inhibitor (MPT0E014; 50 mg/kg/rat daily for 7 days). Results: Compared with the control rats, T2DM and T2DM rats treated with MPT0E014 exhibited elevated blood glucose levels and similar body weights. However, T2DM rats treated with MPT0E014 and control rats had a smaller left ventricular end-diastolic diameter compared with the T2DM rats. The control and T2DM rats treated with MPT0E014 had greater protein expression of cardiac phosphorylated (p)-5’adenosine monophosphate - activated protein kinase α 2, light chain 3-II, Beclin-1, glucose transporter 4, p-protein kinase B, and insulin receptor substrate-1 (Ser 307) compared with T2DM rats. In addition, control and T2DM rats treated with MPT0E014 had decreased cardiac protein expression of cleaved PARP1, p-mTOR-S2448, p-P70S6K-Thr-389, RAGE, tumor necrosis factor-α, and interleukin-6 compared with T2DM rats. Conclusion: The present study demonstrated that MPT0E014 may improve cardiac function in T2DM rats by modulating myocardial autophagy, inflammation and insulin signaling.

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PD-15

DECREASED RISK OF GINGIVITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS USING CALCIUM CHANNEL BLOCKERS HSIN-HUNG CHEN Nantou Christian Hospital

Abstract Objective: To evaluate the association between gingivitis and the use of calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus (DM). Methods: We used a nationwide health insurance claims database to select patients with type 2 DM and aged 20 years or older as the study population who received CCBs or without received CCBs between 2000 and 2008.

Cox proportional hazards regression analysis was used to calculate the hazard ratio of gingivitis in these 2 groups. Results: The incidence density rates of gingivitis were 16.7 and 10.7 per 1000 personyears for the non-CCB and CCB groups, respectively. After adjustments for sex, age, comorbidity, and medications, the risk of gingivitis in patients with type 2 DM using CCBs decreased by approximately 25% compared with that of those without using CCBs. The male patients with type 2 DM using CCBs had a 0.72-fold lower risk of gingivitis than did those not using CCBs. Diabetic patients with CCBs was significantly associated with a declined risk of gingivitis than those without CCBs in both study group without any comorbidity. Conclusions: Data analyses revealed that CCBs can reduce the risk of gingivitis in patients with type 2 DM. Further survey is required for validating the association between CCB usage and risk of gingivitis among patients with type 2 DM.

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Abstract PD-16

FIRST LINE THERAPY WITH METFORMIN AND PEMETREXED IN TYPE 2 DIABETES WITH ADVANCED LUNG ADENOCARCINOMA 1

YI-TING TSAI, 2JIUN-LONG WANG, 3SHIH-NI CHANG, 3CHING-HENG LIN, 4,5 CHUAN-MU CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital 2Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital 3 Department of Medical Research, Taichung Veterans General Hospital 4Department of Life Sciences, National Chung Hsing University, Taichung 5Rong-Hsing Translational Medicine Center, iEGG Center5, National Chung Hsing University, Taichung.

Introduction and Objective: In Taiwan, first line therapy for advanced lung adenocarcinoma (wild type) consider chemotherapy with platin based chemotherapy with Pemetrexed. Among Type 2 Diabetes patients, the Metformim bears the anti-tumor effect. When combination of Metformin and Pemetrexed in first ling therapy in advanced lung adenocarcinoma, the efficacy is unclear. The aim of our study is to try to illustrate the synergistic effect of Metfomrin with Pemetrexed.

Methods: We retrospectively analyzed the National Health Insurance Registered Database (NHIRD) since 2004 to 2013 and figure out the effect of Metformin on overall survival for those type 2 Diabetes with advanced lung adenocarcinoma.

Result: Initially 88,467 patients were enrolled into the study and finally total 495 patients met the criteria. The mean age was about 67.4 ± 9.5 years old and Male predominant. We analyzed the antiDM medication respectively and found Metformin provided the survival benefit for those patients, the hazard ratio (HR) was around 0.61 (P value < 0.001).

Conclusion: In our study, we found preliminary result of Metformin on survival benefit for type 2 Diabetes with advanced lung adenocarcinoma received first line chemotherapy with Pemetrexed.

Further Validation needs prospective randomized control studies.

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PD-17

AUTOIMMUNE POLYENDOCRINE SYNDROMES TYPE 3 PRESENTING WITH SLOWLY PROGRESSIVE TYPE 1 DIABETES MELLITUS, PERNICIOUS ANEMIA AND AUTOIMMUNE THYROID DISEASE : TWO CASE REPORT 2

KAO-MING HSU, 1SZU-HAN LIN, 1DONG-HWA TSAI, 1PEI-YUNG LIAO

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan, R.O.C.;2Department of Internal Medicine, Changhua Christian Hospital, Taiwan, R.O.C.

Background: Autoimmune polyendocrine syndrome (APS) is a rare form of autoimmune disorder involving at least two glandular autoimmune-mediated diseases. APS type 3 is defined as the association between autoimmune thyroid disease and an additional autoimmune disease other than Addison’s disease. Only 3% to 5% of patients with isolated autoimmune thyroid disease have pancreatic islet autoimmunity and/or clinical type 1 diabetes. Autoimmune gastritis clusters with the autoimmune endocrinopathies that include autoimmune thyroiditis and type 1 diabetes mellitus.

Methods: We reports two cases with coexistence of slowly progressive type 1 diabetes mellitus, pernicious anemia and autoimmune thyroid disease.

Results: The first patient is a 78-year-old male diabetic patient presented with recurrent diabetic ketoacidosis, macrocytic anemia, vitiligo vulgaris and autoimmune thyroid disease. The second case is a 64-year-old female diabetic patient present with frequent hypoglycemia, macrocytic anemia with jaudice and thrombocytopenia, Alopecia and autoimmune thyroid disease. Both of them have an initial non-insulin-dependent stages and delay in the diagnosis of latent autoimmune diabetes of adult, pernicious anemia related to autoimmune gastritis and occult autoimmune thyroid disease. They were treated with intensive insulin therapy as well as intramuscular vitamin B12 injection; therefore, glycemic control became stable and anemia was alleviated.

Conclusions: In cases of concomitant diabetes and macrocytic anemia, the potential existence of latent autoimmune diabetes of adult and other associated autoimmune disease should be taken into account in daily practice. As both pernicious anemia and autoimmune thyroiditis tend to appear long after the onset of diabetes, particular attention must be paid to them.

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Abstract PD-18

HYPERDENSE BASAL GANGLIA IN NONKETOTIC HYPERGLYCEMIA WITH STROKE-LIKE PRESENTATION 1

SHIH-CHE HUA, 2PO-YEN YEH

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.; 2Division of Neurology, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.

The imaging finding of lateralizing/asymmetric basal ganglia lesions (hyperdense on computed tomography) with clinical finding of hemichorea-hemiballism is highly suggestive of nonketotic hyperglycemia. We presented an unusual case of a patient with vague stroke-like complaints, not typical chorea, and imaging findings notable for lateralizing basal ganglia lesions. A 64 year-old gentleman with past medical histories of hypertension and dyslipidemia presented to the emergency department with a one week history of progressively worsening general weakness, especially left side. The patient’s neurologic exam revealed mild left upper and lower limb muscle power deficits (4+). The remainder of the neurological exam was unremarkable. Due to concern for acute ischemia, a non-contrast head computed tomography exam was performed which demonstrated hyperdensity in right basal ganglia (Fig. 1). Laboratory evaluation was notable for serum glucose of 1128 mg/dL and osmolarity of 339 mOsm/kg (normal 275-295). The patient was admitted later with impression of newly diagnosed diabetes mellitus with nonketotic hyperosmolar hyperglycemia.

His symptoms improved and his neurologic exam returned to baseline with insulin administration and the normalization of his serum glucose level. Therefore, the presumed etiology for his initial neurologic symptoms was a global neurologic dysfunction secondary to hyperglycemia. After a four day hospitalization, the patient was discharged in his usual state of health and instructed to follow-up as an outpatient. There have been not a few case reports of chorea or another movement disorder in association with this pathognomonic imaging appearance of the basal ganglia. Here we presented a rare case of subjective sensation of generalized weakness and mild left hemiparesis on neurologic exam, initially concerning for a new ischemic insult. Hyperdense basal ganglia in nonketotic hyperglycemia may present as mimicking storke-like signs, instead as hemichorea-hemiballism.

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PD-19

RISK OF MORTALITY INCREASES IN DIABETIC NEPHROPATHY IN UREMIA WITHOUT TREATMENT OF ANTI-DIABETIC AGENTS OR INSULIN 1

CHUNG-ZE WU, 2JIN-SHUEN CHEN, 3LI-CHIEN CHANG, 4YUH-FENG LIN, 1JIUNNDIANN LIN, 5DEE PEI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital; 4Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 2Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital; 3 School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, R.O.C.; 5 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, R.O.C.

Background: The suggestion “diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs” from our group has been published.

However, the retrospective cohort study was between 2002 and 2007. In the period, in Taiwan, oral anti-diabetic agents (OADs) was sulfonylurea, alpha-glucosidase inhibitors, meglitinide, and thiazolidinedione. New OADs were market in Taiwan after that period. A new longitudinal 5-year (2011 – 2015) observational study was conducted to investigate whether the use of anti-diabetic medications, including new OADs, affected survival rates of diabetic dialysis patients or not.

Methods: A retrospective cohort study by data sample of 2 million patients from Taiwan’s National Health Insurance Database surveyed patients with diabetes who began dialysis between 2011 and 2015. The population were divided using and non-using anti-diabetes medicine. Furthermore, the populations in non-using anti-diabetes medicine were sub-divided to only insulin, only oral antidiabetes agent (OAD), and combination of insulin and OADs. Survival prognosis, causes of death, and effects on survival prognosis of different classes of anti-diabetic medicine (sulfonylurea, a-glucosidase inhibitors, meglitinide, thiazolidinedione, DPPIV inhibitor, GLP-1 receptor agonist) were analyzed.

Results: There were 1,887 patients with diabetic nephropathy in uremia enrolled and followed up for 5 years or to date of death. Of 882 patients died in the period, those non-using anti-diabetic medicine (62.36 %) had a higher mortality rate than those using anti-diabetic medicine (41.98%). After the multivariate analysis, group of combination of insulin and OADs had the lowest risk of death (HR 0.59, 95 % CI 0.57–0.61), followed by OADs alone (HR 0.68, 95 % CI 0.52–0.70) and then insulin alone (HR 0.781, 95 % CI 0.72–0.83). Furthermore, there were no significant differences in survival prognosis for the six classes of anti-diabetes medicine.

Conclusion: This 5-year observational study results suggested that diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs. Despite insulin therapy, appropriate OADs should play an important role in treating these patients.

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Abstract PD-20

BASELINE HBA1C LEVEL AND BODY MASS INDEX PREDICT EFFICACY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS IN TAIWANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS 1

YI-HSIN LIN

1

Division of endocrinology and Metabolism, department of internal Medicine, Taiwan Adventist Hospital

Background/Purpose: Dipeptidyl peptidase-4(DPP-4) inhibitors are the most popular oralantidiabetic drugs (OADs) in recent 20 years because of low hypoglycemic risk, intermediate efficacy (HbA1c): 0.5-0.9%, neutral effect on body weight change, convenience for usage (mostly once daily) and rare major side effects. The purpose of the study was to find out the important predictors for efficacy of naïve use of DPP-4 inhibitors in Taiwanese patients with type 2 diabetes mellitus (T2D).

Methods: It was a retrospective observational study. 193 T2D patients (122 males) were naïve DPP-4 inhibitor users at the age 58.0 ± 12.6 years with disease duration 5.4 ± 4.7 years, body mass index (BMI) 26.1 ± 4.3 kg/m2 and eGFR 95.9 ± 27.0 (mL/min/1.73 m2) were assessed for HbA1c in 6 months.

Results: 193 T2D patients used DPP-4 inhibitors as 2nd or 3rd line of OADs (2.8 ± 0.7 kind of OADs). The efficacy was HbA1c: 1.1 ± 1.2% in average. 138(71.5%) patients were effective (HbA1c ≥ 0.5%) with mean HbA1c(1.5 ± 1.1%, compared with non-effective (HbA1c < 0.5%) group, 0.0 ± 0.4%, p < 0.001). The efficacy was significantly better in statistic in the BMI < 25 group than the BMI ≥ 25 group (HbA1c(%) (1.4 ± 1.4 vs. 0.9 ± 0.9, p = 0.012). The higher baseline HbA1c (%) level group (< 7.5 vs. 7.5-9.0 vs. > 9.0) had significantly better efficacy (HbA1c (%) (0.4 ± 0.5 vs. 0.9 ± 0.8 vs. 2.3 ± 1.5, p < 0.001), compatible with positive association in single regression analysis. Finally, gender, age, duration of T2D, number of kinds of OADs and eGFR level played no role in efficacy.

Conclusion: Using DPP-4 inhibitors as 2nd or 3rd line of OADs, the study predicted higher baseline HbA1c level and lower BMI as important factors for efficacy of DPP-4 Inhibitors in Taiwanese diabetic patients.

Keywords: dipeptidyl peptidase-4 inhibitor, type 2 diabetes, HbA1c, predictor of efficacy

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PD-21

REVIEW OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS INDUCED EU-GLYCEMIC DIABETIC KETOACIDOSIS : POSSIBLE PATHOPHYSIOLOGY AND CONTRIBUTING FACTORS 1

YI-HSIN LIN

1

Division of endocrinology and Metabolism, department of internal Medicine, Taiwan Adventist Hospital

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the newest class of oral antidiabetic drugs (OADs), approved to be a second-line OAD for type 2 diabetes in Taiwan since 2016. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had both released statements associating the use of SGLT-2 inhibitors may increase the risk of eu-glycemic diabetic ketoacidosis(euDKA). This review reveals the possible pathophysiology with a chain of metabolic adaptions to decrease plasma glucose and increase plasma ketone bodies through pancreas, kidney, liver and adipose tissue. Moreover, euDKA is a potential and rare complication of treatment with SGLT-2 inhibitors when coexisting with triggering factors. It is an emerging challenge for clinical physicians and patients treated with SGLT-2 inhibitors. Therefore, literature review of possible pathophysiology and contributing factors is presented in order to make more attentions in public.

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Abstract PD-22

CASE REPORT: THE SAFETY AND EFFICACY OF LIRAGLUTIDE IN PATIENT WITH MITOCHONDRIA DIABETES AND PSORIASIS IN SHORT-TERM USE JIN-WEI HUANG Lohas Clinics

A 31-year-old female with normal body weight, mitochondrial diabetes, asthma, and psoriasis was under basal-bolus insulin therapy for more than 10 years. Her mother was diagnosed of mitochondrial diabetes with 3,243 nucleotide pair (NP) mutation about 30 years ago. Due to the progress of insulin control in past 3 to 6 months even under intensive diet control and self-monitor blood glucose, the glucagon-like peptide-1 receptor (GLP1) agonist liraglutide was added for better sugar controlled.

The patient experienced marked improved in her psoriasis after 2 to 3 months of treatment course.

The severity of Itching and the area of psoriasis was improving. The Hba1c and rates of hypoglycemia was also improving. However, the body weight did not been changed. The treatment of liraglutide was shifted to empagliflozin. Psoriasis progress again with large area of psoriasis and itching progress.

The empagliflozin was shifted back to liraglutide. After 2 months of re-add liraglutide, the severity of itching and the area of psoriasis was improving again. The HbA1C and rates of hypoglycemia was improving again. However, the body weight was kept stationary. Except of mild nausea sensation, no adverse effect was observed during this treatment course. There are few study focus on obesity patient with diabetes and psoriasis received the treatment of liraglutide. There reports disclosed the benefit of liraglutide treatment for both diabetes and psoriasis. However, this is the first case of patient with mitochondrial diabetes and psoriasis received the liraglutide therapy. This case report disclosed the safety and efficacy of liraglutide for patient with mitochondria diabetes and psoriasis in short-term use.

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PD-23

CASE REPORT: THE SAFETY AND EFFICACY OF SGLT2 INHIBITOR EMPAGLIFLOZIN IN PATIENT WITH MITOCHONDRIAL DIABETES. 1

JIN-WEI HUANG, 2HUI-CHUN HSU

1

Lohas Clinics; 2 Po Sin Clinc

A 34-year-old male with overweight and mitochondrial diabetes received basal-bolus insulin therapy for more than 10 years. His mother was diagnosed of mitochondrial diabetes with 3,243 nucleotide pair (NP) mutation about 30 years ago. Due to progress of diabetes control, he agreed of SGLT2 inhibitor empagliflozin therapy. After 3 months of therapy, the hba1c(6.0% → 5.6%) and the body weight (69.6kg → 61kg) was improving. The total daily dose of insulin was also decreased during the treatment (92U → 81U). No diabetes ketoacidosis nor lactate acidosis was noted during this treatment course. There are few case report disclosed the efficacy and safety of SGLT2 inhibitor in patient with mitochondrial diabetes. This is the first case report in Taiwan disclosed the safety and efficacy of SGLT inhibitor in patient with mitochondrial diabetes. Most patient with mitochondrial diabetes failure of oral anti-diabetes medication and need insulin for long-term treatment. In this case report, it disclosed that SGLT2 inhibitor for patient with mitochondrial diabetes had similar effect on HbA1C, total daily insulin dose and body weight compared with the effect on patient with type 2 diabetes. There is also no adverse effect observed during this short-term treatment However, there is no muscle power test nor ejection fraction test was done during the treatment course. In conclusion, SGLT2 inhibitor empagliflozin is safe and effect for patient with mitochondria diabetes during shortterm used.

180

Abstract PD-24

A CASE REPORT: ADVANCED PANCREATIC NEUROENDOCRINE TUMOR WITH PRESENTATION OF EPISODIC HYPOGLYCEMIA 1

I-CHEN CHEN, 1YI-HONG ZENG, 1,2CHUN-CHUAN LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

Background: Hypoglycemia is an uncommon clinical problem in patients not being treated for diabetes mellitus. The causes are variable, encompassing drugs, critical illnesses, hormone deficiency, nonislet cell tumor and endogenous hyperinsulinism. Here, we present a young female of episodic hypoglycemia, which was subsequently diagnosed as advanced pancreatic neuroendocrine tumor (PanNET).

Case report: A 35 year-old G1P1 female presented to Mackay Memorial Hospital with episodic consciousness change caused by hypoglycemia since Oct-2015. There was no significant medical disease and contributory family history. Her high was 158 cm and weighted 45 kg with the BMI of 18 kg/m2. She also complained of poor appetite and loss of weight 10kg within 1years. The family stated she can’t be awakened in the morning for several times and serum glucose showed 37mg/dL in emergent department. Her consciousness improved after glucose supplement. Laboratory tests revealed ALT 67 IU/L, Creatinine 0.6 mg/dL, CEA 1.45 ng/ml, AFP 8.63 ng/ml, CA-125 21.65 U/ml, CA-153 10.03 U/ml, CA-199 0.01 U/ml, Chromogranin A (CgA) 997.2 ng/ml, Gastrin 289.00 pg/ml, Prolactin 13.16 ng/ml, Calcium 8.6 mg/dL, intact-PTH 21.34 pg/ml. Prolonged fasting test revealed insulin 14.1 uIU/mL, C-peptide 3.82 ng/mL, serum glucose 47 mg/dL, ACTH 29.95 pg/mL, Cortisol 6.48 ug/dL, IGF-1 220 ng/mL. MRI in July-2016 demonstrated a space occupying lesion abutting the pancreatic tail and metastatic lesions in both lobes of liver. Endoscopic ultrasound guided fine needle aspiration of pancreas tumor and echo-guided biopsy of liver reported neuroendocrine tumor grade 2. Somatostatin analogue (SSA) had been instituted for hypoglycemia and then she received Everolimus treatment.

Discussion: The incidence of neuroendocrine tumor is rising because of the improvement of image investigation. It is categorized as functioning and non-functioning subtype. An insulinproducing Pan-NET causing episodic hypoglycemia is considered to be an insulinoma. Unique features of insulinoma are 90% benign, 90% solitary, 90% intrapancreatic and 90% small (< 2 cm).

The laboratory workup of insulinoma is directed to hyperinsulinism, comprising tests of insulin, C-peptide and proinsulin. In addition to primary imaging as US, CT and MRI, nuclear medicine imaging and invasive study such as EUS (endoscopic ultrasonography) and ASVS (arterial stimulation venous sampling) are often warranted for diagnosis of insulinoma. Once diagnosed, insulinoma is classified into locoregional and metastatic disease. For locoregional insulinoma, there is great chance to cure with surgery. For metastatic disease, the first step of treatment is to manage hypoglycemia 181

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with medications, of which diazoxide and somatostatin analogs (SSA) are most commonly used. The next step is surgery for resectable liver metastasis and systemic antitumor therapy, including SSA, chemotherapy, targeted therapy and peptide receptor radionuclide therapy (PRRT). SSA and targeted therapy have been shown to improve progression-free survival. Although neuroendocrine tumor is not rapid progression, metastatic tumor would cause mortality and morbidity. Early detection and intervention will improve patient’s life quality and survival.

182

Abstract PD-25

ASSOCIATION OF DIABETIC KETOACIDOSIS AND GLYCEMIC CONTROL AMONG TYPE 1 DIABETES WITH PREMIX VS BASAL BOLUS INSULIN THERAPY 1

WEI-YU CHOU, 1SZU-TAH CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

OBJECT: To determine the rate difference of diabetic ketoacidosis (DKA) among children, adolescents and young adults with type 1 diabetes receiving basal bolus or premixed insulin therapy.

RESEARCH DESIGN AND METHODS: 9597 type 1 diabetic patients were retrospectively studied from Chang Gung Research Database (CGRD) between 2001 and 2016, the incidence of DKA requiring hospitalization was analyzed. Exclusion criteria include use of different regimen during the follow-up period, missing data, DKA episode before confirmed diagnosis and insulin exposure and Age > 20. Propensity score with inverse probability of treatment weighting analyses with age, sex and glycated hemoglobin(A1C) as covariates were used to account for relevant confounders.

MAIN OUTCOMES AND MEASURES: Primary outcome was event rate of DKA during the follow-up treatment year. Secondary outcome aims on metabolic indicators control such as glycated hemoglobin levels, triglyceride, LDL and HDL. RESULTS: Of 825 patients (mean age, 12.2 ± 4.31 years; 55%male), 273 used premixed regimen (mean duration, 9.02 years) and 552 used basal bolus regimen (mean duration, 7.82 years). Among those patients, 226 patient using premixed regimen were matched to identical number of patients using basal bolus regimen. In the entire cohort, premixed regimen comparing with basal bolus regimen was associated with higher rates of DKA (4.53 vs 10.62 per 100 patients; P < 0.001). The trend was also found in matched cohort. (HR 2.0, P = 0.0371). In the cox regression hazard model, the glycated hemoglobin level showed significant influences on the incidence of DKA. (HR 1.354, P < 0.001) The influences were not significant if the A1C level lower than 7.5%. In the secondary outcome, A1C levels were lower with basal bolus regimen than with premixed regimen (8.87 ± 1.62% vs 10.02 ± 2.03%; P < 0.001). Triglyceride level were lower for basal bolus regimen compared with premixed regimen (88.32 vs 109.1; P = 0.015). There was no significant difference in HDL and LDL level between both treatment regimens.

CONCLUSIONS: Patients used premixed insulin regimen may increase DKA event rate comparing to basal bolus regimen in T1D children, adolescents and young adults.

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PD-26

REGUATION OF THE GUT–LIVER AXIS BY GLP-1 RECEPTOR AGONIST TO ATTENUATE THE FATTY LIVER 1

HSIN-YING CHIOU, 1HE-JIUN JIANG, 2KUN-BOW TSAI, 1WEI-WEN HUNG, 1 PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University,Taiwan, R.O.C.; 2Department of Pathology, Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, R.O.C.

Background: Prevalence of the non-alcoholic fatty liver disease (NAFLD) is estimated 20-30% in Western countries and up to 18% in Asia with an increasing trend in the whole world. Diabetes and aging could deteriorate and fasten the progression from NAFLD to steatohepatitis and end-stage liver diseases. Until now, it is still lack of effective medicine to treat NAFLD. The gut-liver axis is balanced by the homeostasis of gut microbiome, intestinal and liver immunity to response the dietary nutrition.

The “Leaky Gut” theory evidenced the potential mechanism for the development and progression of the NAFLD and type 2 diabetes. Derangement of gut barrier may lead to translocation of bacteria/ bacteria product into portal circulation, and activate inflammation and NAFLD progression. GLP1 is a gut hormone to amplify the insulin secretion by -cell in a glucose independent pathway. GLP1 receptor agonist (GLP-1 RA) has been proved to have hepato-protective effect in animal and human studies. But the molecular mechanism remains unclear. This study aims to investigate whether GLP1 RA ameliorate hepatic steatosis through gut-liver axis. Methods: Based on a high fat diet (HFD) induced NAFLD model, C57BL/6 mice were divided into 3 groups and fed with chow diet, HFD, HFD combined with weekly s.c. injected GLP-1 RA for 16 weeks. Parameters of body weight, insulin resistance (HOMA-IR), hepatic steatosis and proinflammatory surrogate markers were measured and compared among groups. Protein expressions of the gut barriers integrity, including (1) physical barrier: tight junction (occludin and zona occluden (ZO-1)) and mucus thickness, (2) biological barrier: compositions of fecal microbiota, (3) immunological barrier: macrophage infiltration, were all examined to determine the effect of GLP-1 RA in the regulation of gut-liver axis. Results: The HFD related body weight increment, insulin resistance, and hepatic steatosis were significantly ameliorated

by GLP-1 RA administration. Hepatic expressions of lipogenesis (FASN, ACC, and SREBP-1) and proinflammatory proteins (NLRP3, pNFkB, and IL-1) were also reduced by GLP-1 RA by western blot. The metagenomic analysis of fecal microbiota with16S rRNA sequencing revealed a structural and diversity changes of the intestinal microbiota with the use of GLP-1 RA. Integrity of the gut barriers was apparently impaired by HFD, evidenced by the decreased expression of occludin, ZO-1, mucus thickness, and more macrophage infiltration. However, the above protein expressions all were reversed and attenuated by using GLP-1 RA even in HFD. Discussion and Conclusion: From our 184

Abstract biochemical and histological evidences, GLP-1 RA could regulate the gut-liver axis through improving leaky gut, diminishing the gut inflammation, and modulating the gut microbiota, which may contribute to the attenuation of hepatic steatosis and inflammation. It may also provide the molecular evidence to support the clinical indication of treating NAFLD by GLP-1 RA.

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th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-27

THE GLUCOSE PATTERN CHANGES BETWEEN PREMIXED AND BASAL-BASED INSULIN THERAPIES IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES MELLITUS HSUEH-HUA CHIU, SZU-TAH CHEN, BREND RAY-SEA HSU, WEN-CHUN LU, CHIA-HUNG LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo, Taiwan

Aims/Introduction: The premixed insulin is widely used in patients with type 2 diabetes mellitus (T2DM) in Taiwan even with fluctuated glucose control. The shifting to basal-based regimen is suggested but the comprehensive comparison of glucose patterns between different insulin therapies in patients with poorly controlled T2DM is controversial. The use of recently launched U-300 glargine insulin is supposed to have prolonged action and moderate glucose excursion. The objective of this study is to access glucose pattern changes among patients with shifting insulin therapies by continuous glucose monitoring (CGM).

Material and methods: Outpatient subjects received professional non-real time CGM before and after the insulin change while maintaining their usual diet and daily activities. The relationship of the mean amplitude of glucose excursion (MAGE), different glucose distribution, hyperglycemia, hypoglycemia risk, and estimated A1C among the changes of anti-diabetic therapy were then analyzed.

Results: There were 13 outpatient subjects (age = 61.3 ± 13.9 years; HbA1c = 8.2 ± 1.5%) with poorly controlled T2D enrolled. The pre-change CGM showed frequent lack of awareness of hypoglycemic events as recorded by CGM (3.6 % duration at a day time and 12.9% at night period with hypoglycemia). By comparison between pre- and post-insulin change glucose sensor data, the pre-mixed insulin revealed a higher nocturnal hypoglycemia rate than basal insulin-based therapy (4% vs. 2% duration of a day and 12% vs. 4.3% duration at night, P <0.05).

Conclusions: Hypoglycemia unawareness is not rare in poorly controlled diabetes patients in premixed therapy. The decreased risk of hypoglycemia unawareness may be achieved in these patients after shifting to basal insulin based therapy.

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Abstract BP-1

COMPARABLE GLYCEMIC CONTROL WITH ONCE WEEKLY DULAGLUTIDE VERSUS INSULIN GLARGINE, BOTH COMBINED WITH LISPRO, IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (AWARD-7) 1

THOMAS LEW (PRESENTER ONLY), 2KATHERINE R. TUTTLE, 3MARK C. LAKSHMANAN, 4BRIAN RAYNER, 5ROBERT S. BUSCH, 3D. BRADLEY WOODWARD, 3ALAN G. ZIMMERMANN, 3FADY T. BOTROS 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA;2Providence Health Care, University of Washington, Spokane, WA, USA;3Eli Lilly and Company, Indianapolis, IN, USA;4Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa;5Albany Medical Center Division of Community Endocrinology, Albany, NY, USA

Background: This phase 3 study compared once-weekly dulaglutide (DU) to titrated daily insulin glargine (IG), both combined with insulin lispro, in type 2 diabetes (T2D) patients with moderate-tosevere chronic kidney disease (CKD) stages 3-4.

Methods: Participants were randomised (1:1:1) to DU 1.5mg or DU 0.75mg or IG. Objective: To demonstrate DU noninferiority for A1c change from baseline at 26 weeks.

Results: Baseline characteristics (N = 576) included: [mean ± SD] age 64.6 ± 8.6years, A1c 8.6 ± 1.0%, eGFR 38.3 ± 12.8mL/min/1.73m2, BMI 32.5 ± 5.2kg/m2, daily insulin dose 58.2 ± 31.8 units.

DU was non-inferior to IG for A1c change from baseline at 26 weeks (LSM (SE); -1.2 (0.1)% DU 1.5mg and -1.1 (0.1)% DU 0.75mg, versus -1.1 (0.1)% IG; 1-sided p < 0.001 for both DU doses versus IG); similar results were observed at 52 weeks. Body weight decreased with DU and increased with IG (at 52 weeks: -2.7 (0.5)kg DU 1.5mg and -1.7 (0.4)kg DU 0.75mg, versus +1.6 (0.4)kg IG, 2-sided p < 0.001). The hypoglycaemia rate (glucose ≤ 70 mg/dL) was lower with DU 1.5mg and 0.75mg versus IG (at 52 weeks: 5.8, 7.6 versus 14.4 events/participant/year; p < 0.001, p = 0.004, respectively).

Severe hypoglycaemia was less in DU 1.5mg compared to IG (0 in DU 1.5mg, 5 [2.6%] in DU 0.75mg, and 13 [6.7%] in IG). Nausea, vomiting and diarrhea were more common with DU 1.5mg (19.8%, 13.5%, 17.2%) and 0.75mg (14.2%, 8.4%, 15.8%) versus IG (4.6%, 4.6%, 7.2%).

Conclusions: DU produced comparable glycaemic control, greater weight loss, and lower hypoglycaemia rate versus IG in T2D patients with CKD stage 3-4, with the anticipated gastrointestinal side effects.

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th Annual Meeting of March 10-11, 2018 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

BP-2

DULAGLUTDE TREATMENT IS ASSOCIATED WITH LESS EGFR DECLINE AND GREATER REDUCTION IN ALBUMINURIA IN TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE STAGE 3-4 (AWARD-7) 1

THOMAS LEW (PRESENTER ONLY), 2KATHERINE R. TUTTLE, 3MARK C. LAKSHMANAN, 4BRIAN RAYNER, 5ROBERT S. BUSCH, 3BRAD WOODWARD, 3 ALAN G. ZIMMERMANN, 3FADY T. BOTROS 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Providence Health Care, University of Washington, Spokane, WA, USA; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa; 5Albany Medical Center Division of Community Endocrinology, Albany, NY, USA

Introduction: In short-term studies, dulaglutide (DU) reduced albuminuria and did not change estimated glomerular filtration rate (eGFR) in type 2 diabetes (T2D) patients with normal kidney function. Methods: The AWARD-7 phase 3 trial compared weekly DU (1.5 or 0.75 mg) to daily insulin glargine (IG), both with insulin lispro, in participants with T2D and chronic kidney disease (CKD) stages 3-4. Results: Baseline (BL) characteristics (N = 576) were: eGFR CKD-Epidemiology Collaboration: 38 ± 13 mL/min/1.73 m2 (mean ± SD), urine albumin/creatinine ratio (UACR, mean [median]): 847.2 mg/g (209.3 mg/g), age: 65 ± 9 years, A1c: 8.6 ± 1.0%, duration of T2D: 18 ± 9 years. After 52 weeks, glycemic control was similar for the three treatment arms, both doses of DU proving noninferior to IG for the change in A1c. Mean eGFR (mL/min/1.73 m2 [95% confidence interval]) was not statistically different from BL with DU 1.5 mg (-1.1 [-2.04, 0.2]), while it decreased with DU 0.75 mg (-1.5 [-2.08, -0.2], 2-sided p300 mg/g (N = 258). Conclusion: In participants with T2D and CKD stages 3-4, overall effects on eGFR and UACR were mainly driven by lesser eGFR decline and greater UACR reduction in the DU 1.5 mg group vs IG in participants with UACR > 300 mg/g.

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Abstract BP-3

STEADY STATE BLOOD GLUCOSE CONTROL FOR ONCE WEEKLY DULAGLUTIDE DURING PEAK AND TROUGH CONCENTRATION DAYS 1

THOMAS LEW (PRESENTER ONLY), 2HIREN PATEL

1

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Lilly USA, LLC; Indianapolis, IN, USA; Eli Lilly and Company, Indianapolis, IN, USA; 4Lilly-NUS Centre for Clinical Pharmacology, Singapore

3

Background Dulaglutide (DU), a GLP-1 receptor agonist with a half-life of ~5 days, is administered once weekly in patients with type 2 diabetes. In this post hoc analysis of AWARD-3, the sustainability of DU glycemic effect over a 7-day interval at steady state (attained between 2-4 weeks of dosing) was assessed. AWARD-3 was considered for this analysis as it was the only monotherapy study of DU. Methods Within 1 week prior to the Week 26 visit, patients were asked to collect 8-point self-monitored blood glucose (SMBG) profiles on any 2 non-consecutive days. All evaluable SMBG profiles with valid dosing dates were segregated according to Days 1-7 of a dosing interval. SMBG data on DU peak (Day 2/3) and trough (Day 6/7) plasma concentration days were tested for equivalence. A mixed effect model with random intercept and the time of SMBG collection (peak/trough) as a single covariate, was fitted for statistical analysis. Results Mean daily SMBG concentrations were found to be equivalent between DU peak and trough days for both doses (Table).

Model-predicted DU concentrations (90% prediction interval) also remained above the minimum effective concentration throughout the 7-day period. Conclusion Throughout the weekly dosing interval at steady state, DU has a similar effect on blood glucose control during peak and trough plasma concentration days, as assessed by the change in mean daily SMBG concentrations.

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