106年年會論文摘要集

Agenda

Contents Floor Plan of Conference Rooms ........................................................................................... 2 Daily Program Schedule........................................................................................................... 5 Opening Remarks ...................................................................................................................... 7 Board of Directors ...................................................................................................................... 9 Sponsors ................................................................................................................................... 10 Agenda .......................................................................................................................................11 Abstract PLȈPlenary Lecture (1-4) ................................................................................................. 31 DAROC-TADEȈDAROC-TADE Joint Symposium....................................................... 35 SDȈSymposium-Diabetes (1-5) ........................................................................................ 38 SEȈSymposium-Endocrine (1-5) ..................................................................................... 58 WSȈWorking Group Symposium (1-2) ............................................................................ 73 MEȈMeet the Professor-Endocrine ................................................................................... 79 MDȈMeet the Professor-Diabetes ..................................................................................... 80 APȈ2017 Award ................................................................................................................ 82 YLȈYoung Investigator Research Lecture ........................................................................ 86 SSȈSpecial Session: ESROC-KES Joint Symposium ...................................................... 87 LSȈLunch Symposium (1-12) .......................................................................................... 90 OEȈOral Presentation-Endocrine (1-6) .......................................................................... 105 ODȈOral Presentation-Diabetes (1-6) ............................................................................ 112 PDȈPoster Presentation-Diabetes (1-25) ........................................................................ 120 PEȈPoster Presentation-Endocrine (1-21) ...................................................................... 150 BPȈኆ୧፤НᏪൣ৥ұ (1-10) ...................................................................................... 175 1

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The

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Floor Plan of Conference Rooms

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38

The

4

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Daily Program Schedule

Ϝ๽Җ୾ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬Ᏹཽ ಒ 13 ۪ಒ 2 ԪཽসτཽᄳᏱ೛ःଇཽ ࿾ҭߓ April 8, 2017 (Saturday) Room 201 600 ΢

Room 202 Room 203 80 ΢

Room 401

Room 402AB

Room 402CD

220 ΢

220 ΢

200 ΢

200 ΢

LS6 ᓷؔ‫ݎ‬

LS7 ߢල੬௧ւஷ

ȁȁȁȁȁDAROC-TADEȁ(Room 201) DAROC-TADE Joint Symposium лࡼ΢Ȉ؈ࡧ኉ȁᔝ‫ݎ‬঩ȁ೩ඐ㠈ȁе‫ݾ‬ϰ ᅌᗀ޲Ȉ෇ኋׄȁ೩‫ע‬Ԛȁ‫ݔ‬з៤

8:30-11:30

12:00-13:20

80 ΢

Room 301

LS1 ᗊᒜຆ

LS2 ᛴЫ

LS3 ԋල੏‫ٿ‬

LS4 ᙅ‫ٿ‬

LS5 ᒜ๽

Opening (Room 201) лࡼ΢Ȉ೩ඐ㠈ȁ෇߈।

13:30-13:45

ȁȁȁȁȁPL1ȁ(Room 201) лࡼ΢Ȉ೩ඐ㠈ȁᅌᗀ޲ȈHirofumi Makinoȁ

13:45-14:45

Breakȁ(poster presentation 4 ዃٗၿ ) PE лࡼ΢Ȉ֕ஏᆋȃងีྶȃߚ୊ઊȃ‫݁ݔ‬኉ PD лࡼ΢ : ؄҅ϰȃ؄࠶኉ȃ؄࡛ᑺȃе߹ᑺȃԨ‫ע‬Ꮫ

14:45-15:00

ȁȁȁȁȁPL2ȁ(Room 201) ‫ڑ‬ጓᅌᗀ (103Ԓലяଔᝧዪூл ) лࡼ΢Ȉᔝ‫ݎ‬঩ȁᅌᗀ޲ȈೆҴҖȁȁ

15:00-15:30 ME

OE

SD1

SD2

Adrenal and Pituitary Clinical Pearls

лࡼ΢ȈᑌϮಉ ȁȁȁȁе‫ݾ‬ϰ ȁȁȁȁ؄߫቉

Diabetes Neuropathy Guidelines

Diabetes Treatment

лࡼ΢Ȉᔝ‫ݎ‬঩ ȁȁȁȁեᐢ೾ ᅌᗀ޲Ȉ஼ቂ‫׊‬ ȁȁȁȁ৙ᆱϧ ȁȁȁȁе‫ݾ‬ϰ

15:30-16:45 лࡼ΢Ȉ‫׊ݔ‬ႁ ᅌᗀ޲Ȉ William F. Young, Jrȁ SE1

SE2

OD

Cushing’s Lectures

Immunity and Endocrine Diseases

лࡼ΢Ȉᗃ݃ঢ় ȁȁȁȁചఽֆ ȁȁȁȁࢺΛϧ

лࡼ΢Ȉ༂Љಉ 16:45-18:00 ᅌᗀ޲Ȉചో਷ ȁȁȁȁ஼‫׊‬྾

18:30-21:00

лࡼ΢Ȉചᄹᆌ ȁȁȁȁ྇୊ി ȁȁȁȁጿзᐪ ᅌᗀ޲Ȉᗃ݃ঢ় ȁȁȁȁ‫ݔ‬პᘅ ȁȁȁȁ྇ۤ⧣ ȁȁȁȁҥസϧ ȁȁȁȁ؄जУ Anne Dornhorst

лࡼ΢Ȉ‫ݔ‬ϧ኉ ȁȁȁȁጿջང ᅌᗀ޲Ȉ٫ഢ߈ ȁȁȁȁ‫ݔ‬ᐚᆌ ȁȁȁȁ‫ݔ‬ঢ়ቇ Welcome dinnerȁ(Room 101)

5

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 9, 2017 (Sunday) Room 201 600 ΢ 8:00

SE3

8:40

Genetics of Endocrine and Metabolic Diseases

Room 202 Room 203 80 ΢

220 ΢

220 ΢

200 ΢

200 ΢

WS1

MD

SS

؅݀

Ϝᗻһࢻ

лࡼ΢Ȉ೩ඐ㠈 ȁȁȁȁ༂࡛ᄀ лࡼ΢Ȉٛᓃይ ᅌᗀ޲Ȉ‫ݔ‬ਣ໌ ᅌᗀ޲Ȉ ȁȁȁȁ‫עؖ‬໩ ȁ Wasim Hanif ȁȁȁȁ྇ҘҔ

LS9

LS10

LS11

LS12

ᙅ‫ٿ‬

ᒜ‫ڸ‬ᒜ኉

Լ᡺‫ٺ‬

जමΩ

SD5

SD4 (Ρ)

ȁȁ ȁȁȁPL4ȁ(Room 201) лࡼ΢Ȉ஼ኋ‫܇‬ȁᅌᗀ޲Ȉ஼Љ໚ Breakȁ(poster presentation 4 ዃٗၿ )

14:15-14:30 SE4

AP

YL

Neuroendocrine Tumor

2017 Award Grant Award Lectures

Young Investigator Research Lecture

лࡼ΢Ȉ஼ኋ‫܇‬ ȁȁȁȁᙐም‫ع‬ ᅌᗀ޲Ȉ‫ڻ‬Н‫ڐ‬ ȁȁȁȁ೩ȁᘀ ȁȁȁȁ‫۾ؖ‬౿ ȁȁȁȁࢋ๣ᇉ

Treatment Diabetes Guidance for Complications Diabetes Foot Care in Taiwan лࡼ΢Ȉചఽֆ лࡼ΢Ȉ྇୊ി ᅌᗀ޲Ȉ྇ేᗻ ȁȁȁȁጿзᐪ лࡼ΢Ȉٛᓃይ лࡼ΢Ȉ೩ඐ㠈 ȁȁȁȁе‫ڄ‬Н ȁȁȁȁೆҴҖ ȁȁȁȁ؈ࡧ኉ SE5 ȁȁȁȁဩਐᖑ ᅌᗀ޲Ȉ؄҅ϰ ȁȁȁȁ༂ऊ൞ Debate and ᅌᗀ޲Ȉ֕‫Ⱝݴ‬ ȁȁȁȁೆҴҖ ᅌᗀ޲Ȉ༂ऊ൞ Consensus of ȁȁȁȁ؄जУ ȁȁȁȁ෇ᆱѓ Thyroid Tumor ȁȁȁȁ‫ڻ‬ਐസ ȁȁȁȁඈԚஷ Management in ȁȁȁȁࢺ㦬ᄕ Taiwan ȁȁȁȁചහӏ WS2 лࡼ΢Ȉ෇߈। Gestational ȁȁȁȁቔቄ࣏ Diabetes ᅌᗀ޲Ȉചࡧႁ ȁȁȁȁᒢᘅሊ лࡼ΢Ȉᗃ݃ঢ় ȁȁȁȁ֕ᘅ݈ ȁȁȁȁࢺΛϧ ȁȁȁȁ؄࡛ࠓ ᅌᗀ޲Ȉ؄࡛ࠓ ȁȁȁȁ഍߹՝ ȁȁȁȁ؄҅ϰ

6

SD4 (Κ) Diabetes Complications

ཽসτཽȁлࡼ΢Ȉ೩ඐ㠈 ෇߈।ȁ(Room 201) LS8

13:30-14:15

17:00-17:15

SD3 Diabetes Registry

лࡼ΢Ȉ෇߈।ȁᅌᗀ޲ȈWilliam F. Young, Jr

10:30-12:00

15:45-17:00

Room 402CD

ȁȁȁȁȁȁPL3ȁ(Room 201)

9:30-10:30

15:30-15:45

Room 402AB

Breakȁ(poster presentation 4 ዃٗၿ )

9:15-9:30

14:30

Room 401

Basic Research Osteoporosis of Endocrinology and Metabolism лࡼ΢Ȉ؈ࡧ኉ ȁȁȁȁചᄹᆌ лࡼ΢Ȉ༂࡛ᄀ ᅌᗀ޲Ȉ഍ϧ൳ ȁȁȁȁ‫ݔ‬ϧ኉ ȁȁȁȁ༂ӑύ ȁȁȁȁեᐢ೾ ᅌᗀ޲Ȉೆ৩ㅉ ȁȁȁȁചࡧႁ ȁȁȁȁ஼п‫ܜ‬

лࡼ΢Ȉ஼Љ໚ ȁȁȁȁе‫ڄ‬Н ᅌᗀ޲Ȉ྇୊ി ȁȁȁȁဩਐᖑ ȁȁȁȁച‫ؙ‬໫

12:00-13:20

80 ΢

Room 301

Closingȁ(Room 201) лࡼ΢Ȉ೩ඐ㠈ȁ෇߈।ȁ

Opening Remarks

౪‫ߞٲ‬यມ ө՞ཽসυςȃӒҢ்ԂȈ ᠎ߕө՞ཽসυςӒҢ‫ٿ‬୥ђϜ๽Җ୾ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬Ᏹཽಒ 13 ۪ಒ 2 Ԫཽসτ ཽȊഇႇԒཽᆡீ‫ޠ‬ᅌᗀᇅϸ‫ٵ‬Ȃп෉ཽস૗ᕖூ‫؂‬Ӽ‫ޠུ؂‬ᚃᕜ‫ޤ‬ᜌІ‫׭‬೛Ȃᔗң‫ژ‬ ᖞ‫੿ט‬΢ྲៗȂ‫ٯ‬ᘘ৥୾ርຝഐȄ ҐᏱཽ࣐୾ርᑦ‫੿׎‬ᖓ࿘ (IDF) ‫ཽޠ‬স୾ϟΚȂᑗ྄୥ᇅ୾ርࣁ୞Ȃ‫ٯ‬ණЁѯᢋӶ ୾ር‫ޠ‬ኈ៫ΩȂ‫ש‬উᇅᑦ‫੿׎‬ፐఁᏱཽӶџ (2016) Ԓ 10 У 28-30 Сܼѯі୾ርཽឋϜ ЗȂӔӤᖟᒳ 11th IDF-WPR Congress & 8th $$6' 6FLHQWL¿F 0HHWLQJȂ֝ЖΠ 50 ঐ୾ঢ়Ӕ ॏ 3,185 ՞ᑦ‫੿׎‬ᚃᕜࣻᜱ஠ঢ়୥ᇅȂᖃ‫׺‬ጉ጖኶࣐ 642 ጖Ȃ‫ཽܼٯ‬ϜึߓΠ 566 ጖ः ‫ف‬Ԛ‫ݏ‬Ȃᗝ፝ 203 ՞୾ϲѵ஠ঢ়Ᏹ޲Ȃໍ՘ 254 ൠᅌᗀȂєࢃ୾ር‫ޤ‬ӫᏱ޲ Prof. Takashi KadowakiȃProf. Paul ZimmetȃProf. Mark McCarthyȃProf. Victor J. DzauȃProf. Rury R. HolmanȃProf. Yutaka SeinoȃProf. Hong-Kyu LeeȃProf. Masato KasugaȃProf. Kishio Nanjo Ȍ๊ȂIDF ౫Ӊлৱᇅറ՞лৱ Prof. Shaukat M. SadikotȃProf. Nam H. Cho ηഎΚ‫ڂ‬୥ђȂ ᡲᇅཽ‫୾ޠ‬ር΢ς੽ί౐‫ڔ‬ӠຬȂ‫ࡠ෉ٯ‬ґ‫ٿ‬ԥᐡཽӕԪᇎᖞȶѯᢋȷȄӶԫη्དᗃ ‫ܛ‬ԥ୥ᇅІ‫ڟ‬ֆ‫ޠ‬౪ᆀ‫ٲ‬ȃཽসȃϏձ΢সȂ໸ւ‫׈‬ԚΚൠԚѓ‫୾ޠ‬ርཽឋȄ Ӷཽଡ଼௱৥Р८ȈᏱཽଓଡ଼ၽձᛨۢȂ‫ש‬উϑܼҖ୾ 104 ԒӶѯіҀᛅᄀຘᗋຶᏱ ཽ​ཽ֮ȇཽস΢኶ᛨۢԚߞ ( ҭࠊཽস 1044 ՞ȃ஠ऌᚃ৲ 685 ՞ )ȇۢ෉ѣ໡౪ᆀ‫ཽٲ‬ Іө‫ې‬সཽឋȇණЁϲϸ‫ུݫ‬ചхᗃ஠ऌଌጜᚃଲࠣ፵Ȃۢ෉ᖟᒳ஠ऌଌጜᚃଲຠᠧȇ ᖟᒳःଇཽණ‫ཽٽ‬সᇅөᚃᕜ΢স୥ᇅ᝸៊ఁ‫ࣻي‬ᜱ፟โȇჃᓿԒሇཽস௄‫ٲ‬ᖞ‫ט‬ः‫ف‬Ȃ ᒳ౪ᑦ‫੿׎‬ः‫ف‬ॏฬዪᓿІ ADA ፤Нึߓ၅ֆȇۢ෉‫ޏ׾‬ȶᑦ‫੿׎‬ᖞ‫ྲט‬ៗࡿЖȷᡲᑦ ‫੿׎‬ᚃᕜ΢সԥ२्Іਣ‫ޠ‬୥ՄࡿዀȇණЁҖಁ൸ᚃࠣ፵࡛ဋୋߴҨ᙮਱ӈዂ‫ޏ‬ȃ௱୞ ᑦ‫ี੿׎‬ᓄॏฬȇ୥ᇅ࢈‫ۻ‬ᐡᜱ‫ڐܗ‬уყᡞࣁ୞ཿଡ଼ȇࡈᏳᑦ‫ྲ੿׎‬ៗϵઊࣁ୞ȶᖓӬ ୾зࣩᑦ‫੿׎‬СȷȄґ‫෉ٿ‬೩Ȃࡼ៊ᖞ‫ྲט‬ៗఁ‫ي‬ȃᏱ೛ः‫ف‬ᇅ΢সଌጜ݉ଡ଼ȂණЁᑦ ‫ࠣ੿׎‬፵ྲៗᇅһࢻȂᐍӬᑦ‫੿׎‬ϟၯყ໦ྲៗȂණЁᏱཽ୾ር૗ُ࡚Ȅ ϭԒԒཽϜȂ‫ש‬উ੬րҦུԚҴः‫࣐ف‬ҭ‫ޠޠ‬өȶWorking group ȷᐍӬᑦ‫੿׎‬ө ስ஀‫ޠ‬ሰؒȂηԋ௷Κ‫ق‬ӗᆡீ࿾ҭȈȶDM Neuropathy guidelinesȃDM treatmentȃDM registryȃDM complicationsȃConsensus for DM foot care in TaiwanȃConsensus of thyroid tumor management in TaiwanȃBasic research in endocrinology and metabolismȃGDMȷ ෉ ࡠ ᇅཽ​ཽসউ૗ᕖઊًӼȄӤਣӶϭԒ஡яё‫ ޠ‬2 ҐࡿЖȶѯᢋᑦ‫ڻ੿׎‬ᜟઢစ੿ᡑᖞ‫ט‬ ྲៗࡿЖȷȃȶѯᢋᑦ‫ྲ٘੿׎‬ៗࡿЖȷη஡୉࣐ᚃᕜ΢সᖞ‫ྲט‬ៗ୥ՄȄҐԒ࡚Ԓཽ ፤Н‫׺‬ጉӔॏԥ 58 ጖Ȃπᓟൣ֚ 12 ጖ȃᏪൣ৥ұ 46 ጖ȂөԥຠЩІዪᓿȄ དᗃ‫ܛ‬ԥཽসυςӒҢпІີᇾ୥ђҐᏱཽᇅϲϸ‫ݫ‬ᏱཽϟԒ࡚౿ཽȄણτঢ়ٙᡞ ୋஷȂτཽ༬ᅗԚѓȄ ަყ‫ݳ‬΢Ϝ๽Җ୾ᑦ‫੿׎‬Ᏹཽ ౪‫ߞٲ‬ȁȁȁȁȁȁȁȁᙲα ȁȁȁȁȁȁ

7

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

౪‫ߞٲ‬यມ ᠎ߕө՞ཽস୥ђ 106 Ԓ‫ޠ‬ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬ᏱཽԒཽІᏱ೛ःଇཽȄҐԒ࡚τཽҦ ᑦ‫੿׎‬ᏱཽлᒳȂϲৡ೤დᙵ൳‫׈‬ᐍȄӶϲϸ‫ޠݫ‬፟โР८Ȃ‫ש‬উᗝ፝Π୾ር‫ޤ‬ӫ‫ޠ‬ Professor Williams Young п Endocrine Hypertensionȃ Adrenal and Pituitary Clinical Pearls ୉ Plenary lecture І meet-expert ‫ޠ‬лᚡȇ‫ש‬উηᗝ፝஼Љ໚ఁ௳пҧ‫ޒ‬သಂ੿ᡑ࣐лᚡ ձ Plenary lectureȂ‫ڎ‬՞ఁ௳‫ޠ‬Ᏹ೛ోᎵІᖞ‫ט‬စᡜᙵ൳Ȃࣻ߭‫ܛ‬ԥཽসѠпҦуউ‫ޠ‬ ᅌᗀϜԥ࡟Ԃ‫ޠ‬ᏱಭȄϲϸ‫ݫ‬Ᏹཽԋ௷‫ޠ‬஠ᚡःଇԥ Cushing’s lecturesȃImmunity and endocrine diseasesȃGenetics of endocrine and metabolic diseasesȃNeuroendocrine tumorȃ Debate and consensus of thyroid tumor management in Taiwan ๊ϥঐлᚡȂ‫ܛ‬ᗝ፝ᅌᗀ޲ Ілࡼ΢എ࢑ॷۨΚࡿ‫ޠ‬஠ঢ়ȂϲৡᆡீѠ෉ȄѫѵȂτཽϜ‫ޠ‬፤НዪூዪᅌᗀпІ ཽস‫ޠ‬πᓟ‫ܗ‬Ꮺൣ፤Нൣ๊֚Ȃ҇૗ᡲ୥ђ‫ཽޠ‬সഎ૗஋ԞᛧᅗᅗȄ ᙲણ τཽԚѓȂ‫ܛ‬ԥ‫ཽޠ‬সٙᡞୋஷȂ࿳‫ٲ‬ԄཏȄ

ަყ‫ݳ‬΢Ϝ๽Җ୾ϲϸ‫ݫ‬Ᏹཽ

ሯ␐ⴹ

౪‫ߞٲ‬ȁȁȁȁȁȁȁȁ

8

Board of Directors

Board of Directors

Ȟ‫ۘྲٸ‬Ы์დ௷‫ז‬ȟ

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

෇߈। Fen-Yu Tseng

Standing Executive Board

е‫ڄ‬Н Pei-Wen Wang

ጿջང Keh-Sung Tsai

Executive Board

е‫ݾ‬ϰ Chih-Yuan Wang ؄߫቉ Annie Lee ஼ኋ‫ ܇‬Ching-Chung Chang ചࡧႁ Szu-Tah Chen

ചో਷ Harn-Shen Chen ༂Љಉ Tien-Shang Huang ဩਐᖑ Tjin-Shing Jap ᙐም‫ ع‬Ming-Nan Chien

Standing Control Board

‫ݔ‬ϧ኉ Jen-Der Lin

Control Board

‫׊ݔ‬ႁ Hong-Da Lin

Secretary General

ቔቄ࣏ Feng Hsuan Liu

Deputy Secretary General

֕ஏᆋ Wan-Chen Wu ងีྶ Deng Huang Su

஼Љ໚ Tien-Chun Chang

ߚ୊ઊ Wei-Yih Chiu

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

೩ඐ㠈 Wayne Huey-Herng Sheu

Standing Executive Board

ٛᓃይ Shyi-Jang Shin

ചᄹᆌ Jung-Fu Chen

Executive Board

؈ࡧ኉ Shih-Te Tu ༂ऊ൞ Yu-Yao Huang ചఽֆ Ching-Chu Chen ጿзᐪ Shih-Tzer Tsai

ᗃ݃ঢ় Ming-Chia Hsieh ࢺΛϧ Yi-Jen Hung ྇୊ി Wei-Shiung Yang ༂࡛ᄀ Chien-Ning Huang

Standing Control Board

ೆҴҖ Lee-Ming Chuang

Control Board

եᐢ೾ Low-Tone Ho

Secretary General

‫ݔ‬ਣ໌ Shih-Yi Lin

Secretary

؄҅ϰ Hung-Yuan Li ؄࠶኉ I-Te Lee ؄࡛ᑺ Chien-Hsing Lee

ᔝ‫ݎ‬঩ Tong-Yuan Tai

е߹ᑺ Jun-Sing Wang Ԩ‫ע‬Ꮫ Chih-Hsun Chu ‫݁ݔ‬኉ Kun-Der Lin 9

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan) Would Like to Recognize the Following for Their Support of the 38th Annual Meeting Ȟ‫์ྲٸ‬დ௷‫ז‬ȟ Ωτშਫԥ४ϵѨ

The Leader Book Company Ltd.

Ѕ๽Ң‫׭‬ᚃ᛿޷ӌԥ४ϵѨ

Orient EuroPharma Co., Ltd.

ѯҥ᛿ࠣ޷ӌԥ४ϵѨ

Taiwan Tanabe Seiyaku Co., Ltd

ѯᢋԋල੏‫ٿ‬ᇨ᛿޷ӌԥ४ϵѨ

Astellas Pharma Taiwan, Inc.

ѯᢋԼ᡺‫੉ٺ‬ੀᑲ޷ӌԥ४ϵѨ

Boehringer Ingelheim Taiwan Limited

ѯᢋ‫ݢ‬ҥ᛿ࠣϏཿ޷ӌԥ४ϵѨ

Takeda Pharmaceuticals Taiwan , Ltd.

ѯᢋߢල੬௧ւஷ޷ӌԥ४ϵѨ

AstraZeneca Taiwan Limited

ѯᢋࡷՇ޷ӌԥ४ϵѨ

Bayer Taiwan Co., Ltd.

ѯᢋᒜ‫ڸ‬ᒜ኉᛿ࠣ޷ӌԥ४ϵѨ

Novo Nordisk Pharma (Taiwan) Ltd.

ѯᢋᒜ๽޷ӌԥ४ϵѨ

Novartis (Taiwan) Co., Ltd.

ѯᢋᙅ‫޷ٿ‬ӌԥ४ϵѨ

Eli Lilly and Company(Taiwan), Inc.

ѯᢋᛴЫᚃᕜຩᘟ೪റ޷ӌԥ४ϵѨ

Roche Diagnostics Ltd., Taiwan

ԋջҢᚃ޷ӌԥ४ϵѨ

AmCad BioMed Corporation

؅݀ᚃ᛿ऌ‫޷׭‬ӌԥ४ϵѨ

Conmed Pharmaceutical & Bio-Medical Corporation

ऌ‫ݔ‬቉Ꮳ޷ӌԥ४ϵѨ

Clinico Inc.

जՕւᅮୋஷ޷ӌԥ४ϵѨ

Alere

ज୧ᓷؔ‫޷ݎ‬ӌԥ४ϵѨѯᢋϸϵѨ

Merck Sharp & Dohme (I.A.) Corp. Taiwan Branch

जමΩᚃᕜ౱ࠣ޷ӌԥ४ϵѨ

Medtronic (Taiwan) Ltd.

ീ໩ऌ‫׭‬ԥ४ϵѨ

Boyang Medical Technology Co,Ltd

პ኉᛿ࠣӍཿ޷ӌԥ४ϵѨ

CharDeh Drugs Enterprise Co., Ltd.

ᇄᢋԋὺ߭ԥ४ϵѨ

Ascensia Diabetes Care Taiwan, Ltd.

ᎄ࿆τ᛿ኆ޷ӌԥ४ϵѨ

3¿]HU /LPLWHG

ᗊᒜຆ޷ӌԥ४ϵѨ

6DQR¿ 7DLZDQ &R /WG

10

Agenda

Ϝ๽Җ୾ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬Ᏹཽ ಒ 13 ۪ಒ 2 ԪཽসτཽᄳᏱ೛ःଇཽ С෉ȈҖ୾ 106 Ԓ 4 У 8-9 С ӵᘉ : ѯτᚃଲ୾ርཽឋϜЗ

April 8, 2017 Ȫ201 Roomȫ

PL1

PL1: Plenary Lecture 1

Time

Topic

13:30-13:45

Opening

13:45-14:45 Progression Mechanism and Treatment of Diabetic Nephropathy Update

Speaker

೩ඐ㠈 ෇߈। Hirofumi Makino

April 8, 2017

PL2: Plenary Lecture 2

Ȫ201 Roomȫ

‫ڑ‬ጓᅌᗀ (103Ԓലяଔᝧዪூл )

Time PL2 15:00-15:30

April 9, 2017 Ȫ201 Roomȫ Time PL3

9:30-10:30

April 9, 2017 Ȫ201 Roomȫ Time PL4

Topic Understanding biology of diabetes and related metabolic disorders

Moderator

೩ඐ㠈

Speaker

Moderator

ೆҴҖ

ᔝ‫ݎ‬঩

PL3: Plenary Lecture 3 Topic Endocrine Hypertension

Speaker

Moderator

William F. Young, Jr

෇߈।

PL4: Plenary Lecture 4 Topic

13:30-14:15 Graves’ orbitopathy: An important issue for ophthalmologist and endocrinologist

Speaker

Moderator

஼Љ໚

஼ኋ‫܇‬ 11

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DAROC-TADE Joint Symposium

April 8, 2017 Ȫ201 Roomȫ

ᑦ‫ྲ੿׎‬ៗࠣ፵Ӷѯᢋ‫ུޠ‬ძࣩ Time

Topic

Speaker

Moderator

08:30-09:00 ൣ‫ژ‬ ؈ࡧ኉

09:00-09:10 Opening Remark DAROC-TADE-1

09:10-09:45 ߞ෉ଢᙺΚঐᇄᢋᑦ‫੿׎‬зхϟԬκ ᗎ༗ᇅϸ‫ݚ‬

෇ኋׄ

ᔝ‫ݎ‬঩

DAROC-TADE-2

09:45-10:20 ѯᢋಒ 2 ࠯ᑦ‫੿੿׎‬΢З՗ᆔ੾੿‫ޠ‬ ྲៗԚਞ

೩‫ע‬Ԛ

೩ඐ㠈

‫ݔ‬з៤

е‫ݾ‬ϰ

10:20-10:30 Ӆਁ DAROC-TADE-3

10:30-11:20 ಒ 1 ࠯ᑦ‫੿׎‬ொ‫ٻ‬ңഀ៊‫ܓ‬՗ᑦᆀข ‫ޠ‬ᖞ‫๋ט‬౲ 11:20-11:30 Panel discussion & Closing

12

؈ࡧ኉

Agenda

SD1: Diabetes Symposium 1

April 8, 2017 Ȫ402 AB Roomȫ

Diabetes Neuropathy Guidelines

Time

Topic

SD1-1 15:30-16:00 Overview and pathophysiology of diabetic peripheral neuropathy

Speaker

Moderator

஼ቂ‫׊‬

ᔝ‫ݎ‬঩

৙ᆱϧ

եᐢ೾

е‫ݾ‬ϰ

եᐢ೾

16:00-16:05 Discussion SD1-2 16:05-16:35 Treatment of Diabetic Peripheral Neuropathic Pain in Taiwan 16:35-16:40 Discussion SD1-3 16:40-17:10 Diagnostic tool and education of diabetic peripheral neuropathy

եᐢ೾

17:10-17:15 Discussion

SD2: Diabetes Symposium 2

April 8, 2017 Ȫ402CD Roomȫ

Diabetes Treatment

Time 15:30

Topic

Speaker

Moderator ചᄹᆌ

Opening

SD2-1 15:30-15:50 DM complication: CV risk and event.

(MI, Stroke)

ᗃ݃ঢ়

ചᄹᆌ

SD2-2 15:50-16:10 Time for new forms of insulin?

‫ݔ‬პᘅ

ചᄹᆌ

SD2-3 16:10-16:30 Insulin and incretins: The perfect partnership?

྇ۤ⧣

྇୊ി

SD2-4 16:30-16:50 Cardiovascular outcomes with antihyperglycemic therapy

ҥസϧ

྇୊ി

SD2-5 16:50-17:10 What’s new from updated treatment algorithm?

؄जУ

ጿзᐪ

Anne Dornhorst

ጿзᐪ

SD2-6 17:10-17:40 Gestational Diabetes Management and NICE Guideline Recommendation 17:40-18:00 Q&A

ചᄹᆌ 13

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 9, 2017

SD3: Diabetes Symposium 3

Ȫ402AB Roomȫ

Diabetes Registry

Time

Topic

Speaker

Moderator

SD3-1

8:00-8:15

Taiwan diabetes registry study: An introduction and preliminary report

‫ݔ‬ਣ໌

೩ඐ㠈

SD3-2

8:15-8:40

Biobank in registry study

‫עؖ‬໩

೩ඐ㠈

SD3-3

8:40-9:05

Precision medicine using registry data

྇ҘҔ

༂࡛ᄀ

9:05-9:15

Discussion

All

༂࡛ᄀ

April 9, 2017

SD4: Diabetes Symposium 4

Ȫ402CD Roomȫ

Diabetes Complications

Time SD4-1

Topic

8:40-9:10

An update on diabetes kidney disease

9:10-9:20

Panel discussion

SD4-2 14:30-15:00 Diabetes mellitus and dementia 15:00-15:10 Panel discussion

14

Speaker

Moderator

Wasim Hanif

ٛᓃይ ٛᓃይ

྇ేᗻ

ചఽֆ ചఽֆ

Agenda

SD5: Diabetes Symposium 5

April 9, 2017

Treatment Guidance for Diabetes Foot Care in Taiwan

Ȫ402AB Roomȫ Time

Topic

Speaker

Moderator ೩ඐ㠈

Opening SD5-1 14:30-14:50 Current Status of Diabetic Foot Care in Taiwan and Treatment of Infection

༂ऊ൞

؈ࡧ኉

SD5-2 14:50-15:10 Peripheral Artery Disease Management in Patients with Diabetic Foot Ulcer

෇ᆱѓ

؈ࡧ኉

SD5-3 15:10:15:30 Diabetic Foot Wound Healing and Surgical Treatment

ඈԚஷ

༂ऊ൞

SD5-4 15:30-15:50 2IÀRDGLQJ DQG Prevention of Diabetic Foot Ulcer

ചහӏ

༂ऊ൞

15:50-16:00 Panel Discussion

ೆҴҖ

15

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 8, 2017

SE1: Endocrine Symposium 1

Ȫ201 Roomȫ

Cushing’s Lectures

Time

Topic

Speaker

Moderator

SE1-1 16:45-17:15 Cushing’s syndrome: update and review

ചో਷

༂Љಉ

SE1-2 17:15-17:45 Medical Management of Cushing’s Syndrome

஼‫׊‬྾

༂Љಉ

April 8, 2017

SE2: Endocrine Symposium 2

Ȫ301 Roomȫ

Immunity and Endocrine Diseases

Time

Speaker

Moderator

SE2-1 16:45-17:10 MicroRNA-mediated networks underlie immune response regulation in papillary thyroid carcinoma

٫ഢ߈

‫ݔ‬ϧ኉

SE2-2 17:10-17:35 Lymphocytic Thyroiditis and Papillary Thyroid Carcinoma

‫ݔ‬ᐚᆌ

‫ݔ‬ϧ኉

SE2-3 17:35-18:00 Immune-Related Endocrine Adverse Events

‫ݔ‬ঢ়ቇ

ጿջང

April 9, 2017 Ȫ201 Roomȫ Time

Topic

SE3: Endocrine Symposium 3 Genetics of Endocrine and Metabolic Diseases Topic

Speaker

Moderator

SE3-1

8:00-8:25

Genetics of Endocrine and Metabolic Diseases- Overview and Complex Disease Genetics

྇୊ി

஼Љ໚

SE3-2

8:25-8:50

Mendelian Disease in Endocrine Practice

ဩਐᖑ

஼Љ໚

SE3-3

8:50-9:15

Precision Medicine and Clinical Genetic Testing

ച‫ؙ‬໫

е‫ڄ‬Н

16

Agenda

April 9, 2017

SE4: Endocrine Symposium 4

Ȫ201 Roomȫ

Neuroendocrine Tumor

Time

Speaker

Moderator

SE4-1 14:30-14:55 Chromogranin A and Neuroendocrine Tumors

‫ڻ‬Н‫ڐ‬

஼ኋ‫܇‬

SE4-2 14:55-15:20 Medical Treatment for Neuroendocrine Tumors (NET): Focusing on Pancreatic / Midgut NET and Targeted Therapy

೩ȁᘀ

஼ኋ‫܇‬

SE4-3 15:20-15:45 Future Outlook of GEP-NETs in Taiwan and Treatment Paradigms Update

‫۾ؖ‬౿

ᙐም‫ع‬

SE4-4 15:45-16:10 Neuroendocrine Tumor and Multiple Endocrine Neoplasia Type 1

ࢋ๣ᇉ

ᙐም‫ع‬

April 9, 2017 Ȫ402CD Roomȫ

Topic

SE5: Endocrine Symposium 5 Debate and Consensus of Thyroid Tumor Management in Taiwan

Time

Speaker

Moderator

SE5-1 15:30-15:50 Debate and Consensus of Thyroid Tumor Management in Taiwan

ചࡧႁ

෇߈।

SE5-2 15:50-16:10 Nuclear Medicine-Related Debates and Consensuses of Differentiated Thyroid Cancer Management in Taiwan

ᒢᘅሊ

෇߈।

SE5-3 16:10-16:30 Management of Well Differentiated Thyroid Cancer Tailored Through Risk SWUDWL¿FDWLRQ

֕ᘅ݈

෇߈।

16:30-16:45 Panel Discussion

Topic

෇߈। ቔቄ࣏

17

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 9 , 2017 Ȫ301 Roomȫ Time

WS1: Working Group Symposium 1 Basic Research in Endocrinology and Metabolism Topic

Speaker

Moderator

WS1-1 08:00-08:25 Islet Biology and Transplantation

ೆ৩ㅉ

༂࡛ᄀ

WS1-2 08:25-08:50 Thyroid Cancer Cell Biology

ചࡧႁ

‫ݔ‬ϧ኉

WS1-3 08:50-09:15 Genetic Studies in Obesity and Diabetes

஼п‫ܜ‬

եᐢ೾

April 9, 2017

WS2: Working Group Symposium 2

Ȫ301 Roomȫ

Gestational Diabetes

Time

Speaker

Moderator

WS2-1 15:45-16:10 Diagnosis of Gestational Diabetes Mellitus: An Update

؄࡛ࠓ

ᗃ݃ঢ়

WS2-2 16:10-16:35 Screening of Gestational Diabetes Mellitus: Experience in Taiwan

഍߹՝

ࢺΛϧ

WS2-3 16:35-17:00 Treatment of Gestational Diabetes Mellitus

؄҅ϰ

؄࡛ࠓ

18

Topic

Agenda

April 8, 2017 Ȫ201 Roomȫ

ME: Meet the Professor-Endocrine

Time ME

Topic

15:30-16:45 Adrenal and Pituitary Clinical Pearls

Speaker

Moderator

William F. Young, Jr

‫׊ݔ‬ႁ

April 9, 2017

MD: Meet the Professor-Diabetes

Ȫ401 Roomȫ

Osteoporosis

Time

Topic

Speaker

Moderator ؈ࡧ኉

08:00-08:05 Opening MD-1

08:05-08:35 Pathogenesis of Osteoporosis and Osteoporotic Fractures in Patients with Diabetes

഍ϧ൳

؈ࡧ኉

MD-2

08:35-09:05 Pharmacologic Treatment for Osteoporotic Fractures in Patients with Diabetes

༂ӑύ

ചᄹᆌ

09:05-09:15 Discussion

ചᄹᆌ

19

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 9, 2017

AP: 2017 Award

Ȫ301 Roomȫ

Grant Award Lectures

Time

Topic

Speaker

Moderator ྇୊ി

14:30-14:35 Opening ᓷؔ‫ݎ‬ᓻ‫ؿ‬፤Нዪ AP-1 14:35-14:45 The Link between Non-Alcoholic Fatty Liver Disease and Insulin Resistance by Hepatocyte-Derived Fibrinogen-Related Protein 1

֕‫Ⱝݴ‬

྇୊ി

AP-2 14:45-14:55 Liraglutide Prevents and Reverses Monocrotaline-Induced Pulmonary Arterial Hypertension by Suppressing ET-1 and Enhancing eNOS/sGC/PKG Pathways

؄जУ

ጿзᐪ

AP-3 14:55-15:05 IRAK1, A Target of miR-146b, Reduces Cell Aggressiveness of Human Papillary Thyroid Carcinoma

‫ڻ‬ਐസ

е‫ڄ‬Н

AP-4 15:05-15:15 Cardiotrophin-1 Is Inversely Associated with Obesity in Non-Diabetic Individuals

ࢺ㦬ᄕ

ဩਐᖑ

ᒜ๽ᓻ‫ؿ‬፤Нዪ

15:15-15:30 Panel Discussion and Closing

20

ဩਐᖑ

Agenda

YL: Young Investigator Research Lecture

April 9, 2017 Ȫ401 Roomȫ Time

Topic

Speaker

ೆҴҖ

14:30-14:35 Opening YL

14:35-15:15 The Relationship between Serum ANGPTL6 and the Incidence of Diabetes in Human

؄҅ϰ

Ȫ202 Roomȫ

ೆҴҖ

ٛᓃይ

15:15-15:25 Panel Discussion and Closing

April 9, 2017

Moderator

SS: Special Session ESROC-KES Joint Symposium

Time

Topic

Speaker

ဩਐᖑ Dongsun Kim

12:00-12:10 Opening SS-1 12:10-12:35 Primary Aldosteronism in Korea SS-2 12:35-13:00 Diagnosis and Prognosis of Primary Aldosteronism, TAIWAN-TAIPAI Experience 13:00-13:10 Panel Discussion and Closing

Moderator

Jung Hee Dongsun Kim Kim ֕ϱЁ

ဩਐᖑ

Dongsun Kim ဩਐᖑ

21

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS: Lunch Symposium

April 8 12:00-13:20 April 9 12:00-13:20

April 8, 2017

Room 201

Room 202

Room 203

Room 301

Room 401

LS1 ᗊᒜຆ

Room 402AB

Room 402CD

LS2

LS3

LS4

LS5

LS6

LS7

ᛴЫ

ԋල੏‫ٿ‬

ᙅ‫ٿ‬

ᒜ๽

ᓷؔ‫ݎ‬

ߢල੬௧ւஷ

LS8

LS9

LS10

LS11

LS12

؅݀

ᙅ‫ٿ‬

ᒜ‫ڸ‬ᒜ኉

Լ᡺‫ٺ‬

जමΩ

Topic

Speaker

Moderator

LS1

ᗊᒜຆ

Advances in Insulin and Lipid ManagementGlargine U300 and PCSK-9 Inhibitor Insulin Glargine U300: The Next Generation Basal Insulin to RHGH¿QH The Limits of Control PCSK-9 Inhibitor:Optimal Treatment in Lipid Control

‫ݔ‬პᘅ ߚ࢔୊

೩ඐ㠈

LS2

ᛴЫ

Experience of Shared Medical Appointments in Taiwan

‫࿆ݔ‬ಉ ؄‫߈ڄ‬

࠻ീН

LS3

ԋල੏‫ٿ‬

Update in Gout Management: From Viewpoint of Total Care of Metabolic Syndrome

ᗃડ‫ܒ‬

ചᄹᆌ

LS4

ᙅ‫ٿ‬

MOSA1c, A Multinational Observational Study Assessing Insulin Use: Understanding The Challenges Associated with The Progression of Therapy

֕‫܇‬ᐆ

ጿзᐪ

LS5

ᒜ๽

Clinical Determinants and Characteristics Driving Clinical Decision in Elderly T2DM Management

Ԩ‫ע‬Ꮫ

ऩఃҖ

LS6

ᓷؔ‫ݎ‬

The Role Co-Morbidities Play in The Choice of Anti-Hyperglycemic Agents for Patients with Type 2 diabetes

‫ݔ‬ኋឮ

྇୊ി

LS7

ߢල੬௧ւஷ

The growing evidence of new perspectives in type 2 diabetes treatment- SGLT2 inhibitor and its additional effects

Wasim Hanif

༂ऊ൞

22

Agenda

April 9, 2017

Topic

Speaker

Moderator

LS8

؅݀

Pathogenesis and Treatment in Patients with Diabetic Nephropathy

Yasuhiko Tomino

ٛᓃይ ᙐም‫ع‬

LS9

ᙅ‫ٿ‬

Clinical Application of GLP-1 RA-Are There Any Predictors of EI¿FDF\ IURP Clinical Trials?

ҥസϧ

؈ࡧ኉

Anne Dornhorst

෇߈।

Stefan Kaspers

೩ඐ㠈

‫ݔ‬პᘅ

е‫ݾ‬ϰ

LS10 ᒜ‫ڸ‬ᒜ኉ Clinical Interpretation of Pharmacokinetics and Pharmacodynamics PUR¿OH RI Basal Insulin LS11

Լ᡺‫ٺ‬

Novel Strategies for Improving Long-Term Outcomes in Patients with Type 2 Diabetes

LS12

जමΩ

The Advanced Application of Continuous Glucose Monitoring (CGM) from Monitoring to Diagnosis

23

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 8, 2017 Ȫ401 Roomȫ ਣȁ໣

OE: Oral Presentation-Endocrine ᚡȁҭ

ൣ֚ձ޲

лࡼ΢

OE-1

15:30-15:40 Proteomic Analysis of Anaplastic Thyroid Cancer Cell-Derived Exosome for Tumor Therapy Via LovastatinInduced Differentiation and VildagliptinInhibited Dipeptidyl Peptidase-IV (DPPIV) Activity

е‫ݾ‬ϰ

ᑌϮಉ

OE-2

15:40-15:50 The Clinical SLJQL¿FDQFH RI Oxidative Markers in Well-Differentiated Thyroid Cancer

‫❐ܒݔ‬

ᑌϮಉ

OE-3

15:50-16:00 Urinary Iodine Analysis in A Thyroid Carcinoma Patient Requiring Radioiodine Therapy with Previous Iodinated Contrast Agent Use

еᖆ෡

е‫ݾ‬ϰ

OE-4

16:00-16:10 Neuroendocrine Tumor of the Thymus Associated with Ectopic ACTH Syndrome: Clinical Manifestations of Two Case Studies

ုҰ࠳

е‫ݾ‬ϰ

OE- 5 16:10-16:20 Case Series of Thyrotoxicosis with Liver Failure

‫ݔ‬ԋฟ

؄߫቉

OE-6

ᖨԈ֘

؄߫቉

24

16:20-16:30 Chromogranin A and Synaptophysin Expression in An Aldosterone, Cortisol Co-Secreting Adrenal Incidentaloma

Agenda

April 8, 2017 Ȫ401 Roomȫ ਣȁ໣

OD: Oral Presentation-Diabetes ᚡȁҭ

ൣ֚ձ޲

лࡼ΢

OD-1 16:45-16:55 The Roles of Adiposity on Insulin Resistance, Glucose Effectiveness, First and Second Phase in Aged Subjects

ᇥȁ⢿

ᗃ݃ঢ়

OD-2 16:55-17:05 Major Urinary Protein 1 Interacts with Cannabinoid Receptor Type 1 in Fatty Acid-Induced Hepatic Insulin Resistance in A Mouse Hepatocyte Model

ച෤ᶺ

ᗃ݃ঢ়

OD-3 17:05-17:15 Association of Antihyperglycemic Agents and Gut Microbiota in Type 2 Diabetes Mellitus

ࢺᖩ໴

ചఽֆ

OD-4 17:15-17:25 Inpatient Screen of Retinopathy Predicting Long-Term Mortality in The Diabetic Patients Without AlbuminuriaAn Observational Study

ᗃ໰ซ

ചఽֆ

OD-5 17:25-17:35 Incidence of Chronic Kidney Disease is Related with Hypertriglyceridemia in Type 2 Diabetes Patients - A Prospective Cohort Study in A Community Hospital

೩‫ע‬Ԛ

ࢺΛϧ

OD-6 17:35-17:45 Association between DRB1 and Autoimmune Thyroid Diseases in Patients with Type 1 Diabetes

؄ᐹਤ

ࢺΛϧ

25

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 8-9, 2017

PD: Poster Presentation-Diabetes лࡼ΢Ȉ؄҅ϰȃ؄࠶኉ȃ؄࡛ᑺȃе߹ᑺȃԨ‫ע‬Ꮫ ᚡȁҭ

ಒΚձ޲

PD-01 Case Series of Interferon Induced Type 1 Diabetes Mellitus

༂ιḸ

PD-02 Post-Gastric Bypass Hypoglycemia(PGBH): A Case Report and Literature Review

ചࢨᇖ

PD-03 HbA1c Change and 24-HR Glucose Fluctuation after Vildagliptin Plus Metformin (SPC) Treatment in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Monotherapy: A Prospective, Open-Label Study

؈ࡧ኉

PD-04 The Relationships between Gamma-Glutamyltransferase and Insulin Resistance, Glucose Effectiveness, First- and Second-Phase Insulin Secretion in Old Subjects

ৈ኉ᓓ

PD-05 A Case Report of Acute Kidney Injury after 8 Weeks of EPSDJOLÀR]LQ Use in An Uncontrolled Type 2 Diabetes

؄୾໩

PD-06 Dynamic Changes of Insulin Requirement in Different Meal Times in Patients with Type 1 Diabetes

‫ؖ‬Ϝ‫ޣ‬

PD-07 Testing for HbA1c, in Addition to OGTT, In Patients with No History of Diabetes May Help to Identify Patients with Early ͘-Cell Function Impairment

؄ԈⰩ

PD-08 Indicator Analysis for Responsiveness to Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) in Type 2 Diabetic Taiwanese

ചᛞ໰

PD-09 Metabolic Control in Patients with Type 2 Diabetes Mellitus in A Regional Teaching Hospital in Taoyuan City: A Cross-Sectional Study in Diabetes Shared Care Model Outpatients

؄࿆ಉ

PD-10 A Research of S14 Protein in The Lipogenesis and Metabolic Disorders

ച࡞൪

PD-11 The Relationship between Serum RNase-L Level and Metabolic Syndrome: A Cross-sectional Study

еឋᎪ

26

Agenda

ᚡȁҭ

ಒΚձ޲

PD-12 Expression and PXUL¿FDWLRQ RI &QW$ Protein from Microbiota

෇ς൪

PD-13 Seasonal Variation of HbA1c can Be Independent of The Annual Changes of Glycemic Control in Each Season

ചࢨᏛ

PD-14 The Jointed Effect of Vascular Cell Adhesion Molecule-1 and Coronary Artery Disease on Brain-Derived Neurotrophic Factor

؄࠶኉

PD-15 Association between Systolic Blood Pressure and Future Risk of Mortality in Diabetic Subjects among U.S. Adults

ऩ๼ߋ ഍‫ܒ‬൪

PD-16 A Case Report: Use of GLP 1 Agonist in An Obese Type 2 Diabetes Mellitus Patient with Weight Loss Failure After Vertical Banded Gastroplasty

ചྷН

PD-17 Painful Diabetic Polyneuropathy is Associated with 3-Year All-Cause Mortality in T2DM

Աဒਫ

PD-18 Hypoglycemia-Related Emergency Department Visits in Patients with Type 2 Diabetes: Focusing on DPP-IV Inhibitor vs. Sulfonylurea Treatment on Top of Metformin

ചࣵԄ

PD-19 Obesity/Overweight Reduces The Risk of Active Tuberculosis: A Nationwide Population-Based Cohort Study in Taiwan

ᚠҘᙵ

PD-20 Factors Associated with Visit-To-Visit Glucose Variability in Patients with Type 2 Diabetes

ച࢔❒

PD-21 Hypertriglyceridemia is A Residual Risk Factor Associated with New-Onset DKD in Type 2 Diabetic Patients Without Hypertension

ೆҴঘ

PD-22 2SWLPL]LQJ Glycemic Control in Tube-Fed Diabetic Patients with Continuous Glucose Monitoring

؈ཿᙵ

PD-23 Long-Term Glycemic Control after 5 Years of Health Education on Glycemic Control during Holiday Time in Type 2 Diabetic Patients

ച߀࿋

PD-24 One Stop Service of Diabetic Integrated Care

ചࢍී

PD-25 Genetic Variants of Urokinse Plasminogen Activator in Subjects with Type 2 Diabetes Mellitus and Diabetic Nephropathy in Uremic State

֕‫܇‬ᐆ

27

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 8-9, 2017

PE: Poster Presentation- Endocrine лࡼ΢Ȉ֕ஏᆋȃងีྶȃߚ୊ઊȃ‫݁ݔ‬኉ ᚡȁҭ

ಒΚձ޲

PE-01 Cocurrent Graves’ Disease and Bilateral Carotid Artery Stenoses (Moyamoya Disease): A Case Report

߇ςল

PE-02 Alternative Uptake (Flip-FORS RI 0HWDLRGREHQ]\OJXDQLGLQH 0,%*

and Fluorodeoxyglucose (FDG) in Detecting Catecholamine Producing Tumor: Demonstrate 3 Cases

‫ྍݔ‬ஊ

PE-03 The Occult Ectopic ACTH Syndrome Treated with Metyrapone- A Case Report

᎓സЩ

PE-04 Tumoral Calcinosis in Chronic Hemodialysis with Hyperphosphatemia - A Case Report

‫ݔ‬ው‫ݡ‬

PE-05 A Case Report of Von Hippel-Lindau Disease

‫ݔ‬Ҟ‫ܒ‬

PE-06 The Strategy of Cushing’s Disease Without Initial Manifestation of Pituitary Adenoma in MRI Examination: A Case Report

༂୊ህ

PE-07 Case Report: A Case of Uncontrolled Graves’ Disease Presenting with Mitral Valve Chordae Rupture with Severe Mitral Regurgitation

‫࣢يݔ‬

PE-08 Thyroid Storm: Case Report

‫࣢يݔ‬

PE-09 A Case Report: Thyroid Volume in A Patient with Hasimoto Thyroiditis is Progressively Reduced As A Sequela of Chemotherapy for Lymphoma

ചྷН

PE-10 Parathyroid Carcinoma Mimicking Anaplastic Thyroid Carcinoma

ചዬඐ

PE-11 Transient Thyroid Swelling Following Fine Needle Aspiration: A Rare Complication of Thyroid Fine Needle Aspiration

ᛴт݀

PE-12 Rare Organ Metastases in A Rare Skin Neuroendocrine Tumor

ࢺ๝⼆

PE-13 A Case of Hypopituitarism Presenting with Galactorrhea

ചዬඐ

28

Agenda

ᚡȁҭ

ಒΚձ޲

PE-14 A Cross-Sectional Retrospective Study to Identify Indicators for Initiating Thyroid Hormone Replacement Therapy in Patients with Subclinical Hypothyroidism

ചੵᆬ

PE-15 A Case Report: Acute Suppurative Thyroiditis with Gas Formation Originating from Urinary Tract Infection

ചྷН

PE-16 Hypercalcemia from Suspected Matastatic Gastrointestinal Stromal Tumor (GIST) to The Lung: A Case Report

ച୊ল

PE-17 A Cyclin-Dependent Kinase Inhibitor, Dinaciclib in Preclinical Treatment Models of Thyroid Cancer

‫ݔ‬ᐚᆌ

PE-18 Rathke’s Cleft Cyst Induced Panhypopituitarism Presented with Recurrent Hyponatremia

࿳හஷ

PE-19 Hyperaldosteronism Related Hypokalemia in Anorexia Nervosa, A Case Report

ᒧპጝ

PE-20 Deduced Mechanism of Epimedium Induced Myotube Hypertrophy in C2C12 Cells

‫ݔ‬ઊԋ

PE-21 Infundibulo-Neurohypophysitis with Diabetes Insipidus: A Case Report

ചȁᄖ

29

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

April 8-9, 2017

BP 1-10 ኆ୧፤НᏪൣ৥ұ ᚡȁҭ

BP-01 Rationale, Design Features, and Baseline Characteristics: The Heart Institute of Japan-PRoper Level of Lipid Lowering with Pitavastatin DQG (]HWLPLEH LQ Acute coronary Syndrome (HIJ-PROPER)

‫׺‬ጉ൑՞ Tanabe

BP-02 Haemodynamic Effects of Combination Therapy with The DPP4 Inhibitor Linagliptin and Renin-Angiotensin System Inhibitors in Patients with Type 2 Diabetes

LILLY &BI

BP-03 (IIHFW RI (PSDJOLÀR]LQ RQ $OEXPLQXULD LQ 3DWLHQWV ZLWK 7\SH Diabetes and High Cardiovascular Risk

LILLY &BI

BP-04 5DSLG 2QVHW RI 5HQDO (IIHFWV ZLWK (PSDJOLÀR]LQ LQ 7\SH 'LDEHWHV A Cumulative Renal Event Analysis Over Time in the EMPA-REG OUTCOME® trial

LILLY &BI

BP-05 Heart Failure Hospitalisation or Cardiovascular Death with EPSDJOLÀR]LQ LQ Patients with Type 2 Diabetes and High Cardiovascular Risk: Analysis Over Time

LILLY &BI

BP-06 Factors Associated with Insulin Adherance Among Patients with Type 2 Diabetes: The Mosaic Study

LILLY

BP-07 Demographic and Clinical Factors May Predict Insulin Progression and Glycemic Control among Patients with Type 2 Diabetes Using Insulin: Learning form The Mosaic Study

LILLY

BP-08 (I¿FDF\ DQG Safety by Baseline A1C with Once-Weekly Dulaglutide in The Award Program

LILLY

BP-09 (I¿FDF\ DQG Safety by Duration of Diabetes with Once-Weekly Dulaglutide in The Award Program

LILLY

BP-10 Assessing The Economic Burden of Patients with Hypoglycemia in Taiwan Using The National Health Insurance Research Database (NHIRD)

LILLY

30

Abstract

PL-1

PROGRESSION MECHANISM AND TREATMENT OF DIABETIC NEPHROPATHY UPDATE HIROFUMI MAKINO, M.D., PH.D. Director, Okayama University Hospital

Diabetic nephropathy is one of the most serious complications of diabetes. End-stage renal disease (ESRD) due to diabetes is the leading cause and the incidence is very high especially among FRXQWULHV ORFDWHG LQ :HVWHUQ 3DFL¿F 5HJLRQ $FFRUGLQJ WR 865'6 $QQXDO 'DWD 5HSRUW PDQ\ Asian countries headed the list of percentage of incident patients with ESRD, compared to Western countries. Interestingly, Asian countries with high salt intake revealed high incidence of ESRD, meanwhile, Western countries with low salt intake demonstrated low incidence of ESRD. Diabetic nephropathy is characterized by accumulation of extracellular matrix in glomeruli, called exudative, diffuse and nodular lesions. They are finally followed by glomerulosclerosis and LQWHUVWLWLDO ¿EURVLV DQG LQ VXFK VLWXDWLRQ WKH SDWLHQWV LQHYLWDEO\ XQGHUJR GLDO\VLV WKHUDSLHV DQG UHQDO transplantation to survive. :H KDYH EHHQ HPSKDVL]LQJ WKH LPSRUWDQFH RI PLFUR LQÀDPPDWLRQ LQ WKH SURJUHVVLRQ RI GLDEHWLF nephropathy and the identification of key molecules would facilitate to the development of new WKHUDSHXWLF VWUDWHJLHV :H IRFXVHG DQG HPSKDVL]HG RQ WKH DQWL LQÀDPPDWRU\ DQG DQWL R[LGDWLYH HIIHFWV of glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP4) inhibitors, which ameliorated the progression of diabetic nephropathy in rodent models. We also investigated the EHQH¿FLDO UROH RI VRGLXP JOXFRVH FRWUDQVSRUWHU 6*/7 LQKLELWRUV RQ WKH SURJUHVVLRQ RI GLDEHWLF nephropathy using various animal models and reported SGLT2 inhibitors primarily ameliorates oxidative stress and inflammation in proximal tubular cells. New therapies such as incretin-related GUXJV DQG 6*/7 LQKLELWRUV ZRXOG KDYH WKH DGGLWLRQDO EHQH¿W LQ WKH SURWHFWLRQ RI GLDEHWLF QHSKURSDWK\ beyond blood glucose control.

31

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PL-2

UNDERSTANDING BIOLOGY OF DIABETES AND RELATED METABOLIC DISORDERS L-M CHUANG Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Diabetes and related metabolic disorders are the most challenging health problems in this century.

During the past decades, it is noted an increasing trend of type 2 diabetes, esp. in young population, in the Asian countries including Taiwan. The causes of these metabolic disturbances are multifactorial basis involving both genetic and environmental factors with a seemingly similar underlying defect in insulin sensitivity. To tackle these health problems, we took a wide variety of approaches in the past, mainly translational approach to study the issues of interest, testing the central defect of the disorders, LGHQWLI\ WKH ULVN IDFWRUV RI WKH GLVRUGHUV HVWDEOLVK WKH UROH RI UHVSHFWLYH JHQHV LQ GLVHDVH FRQWH[W GH¿QH JHQHWLF VLJQDWXUH RI FHUWDLQ FRQGLWLRQV DQG ¿QG RXW SRWHQWLDO QHZ WUHDWPHQW In this talk, I will describe our experience of the approaches to study both clinical and basic aspects of the complex diseases such as diabetes and the related metabolic disorders. Based upon the HVWDEOLVKHG WHFKQRORJLHV DQG H[SHULHQFH LQ WKLV ¿HOG ZH H[SHFWHG WR KDYH EHWWHU XQGHUVWDQGLQJ RI WKH etiology of those complex diseases and look forward to developing novel therapeutic opportunities. We DQWLFLSDWH RXU \RXQJ JHQHUDWLRQ ZLWK FRQ¿GHQFH WR GHYHORS QHZHU WHFKQRORJLHV DQG FRQFHSWV WR VROYH the nature of these ever-expanding disorders that affect our population now and in the coming years.

32

Abstract

PL-3

ENDOCRINE HYPERTENSION WILLIAM F. YOUNG, JR., MD, MSC Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

Hypertension may be the initial clinical presentation for at least 15 endocrine disorders. An accurate diagnosis of endocrine hypertension provides clinicians with the opportunity to render a VXUJLFDO FXUH RU WR DFKLHYH DQ RSWLPDO FOLQLFDO UHVSRQVH ZLWK VSHFL¿F SKDUPDFRORJLF WKHUDS\ ,Q WKLV presentation I will answer questions about and provide clinical tips on the diagnosis and treatment of primary aldosteronism and pheochromocytoma.

Primary aldosteronism (PA). When can the clinician ignore the clinical practice guideline ³UXOHV´ IRU FDVH GHWHFWLRQ DQG FRQ¿UPDWRU\ WHVWLQJ DQG ZK\" 'R VSLURQRODFWRQH DQG HSOHUHQRQH UHDOO\ QHHG WR EH GLVFRQWLQXHG LQ DOO SDWLHQWV XQGHUJRLQJ DQ HYDOXDWLRQ IRU 3$" +RZ DFFXUDWH LV FRPSXWHG tomography in distinguishing between unilateral aldosterone-producing adenoma and bilateral LGLRSDWKLF K\SHUSODVLD" 'R DOO SDWLHQWV ZKR ZDQW WR SXUVXH WKH VXUJLFDO WUHDWPHQW UHTXLUH DGUHQDO YHQRXV VDPSOLQJ" +RZ VKRXOG ZH XVH WKH UHVXOWV RI WKH UHFHQW 63$57$&86 WULDO" ,Q SDWLHQWV PDQDJHG PHGLFDOO\ KRZ GR \RX GHWHUPLQH WKH FRUUHFW GRVDJH RI WKH PLQHUDORFRUWLFRLG UHFHSWRU DQWDJRQLVW" Pheochromocytoma and Paraganglioma (PPGL). How has the clinical presentation of PPGL FKDQJHG RYHU WKH SDVW \HDUV" :KHQ VKRXOG ZH VXVSHFW WKDW D SDWLHQW PD\ KDYH D 33*/" :KLFK PHGLFDWLRQV GR DQG ZKLFK PHGLFDWLRQV GR QRW LQWHUIHUH ZLWK FDVH GHWHFWLRQ WHVWLQJ IRU 33*/" :KHQ should be use suppression testing with clonidine or provocative testing with histamine or glucagon to VFUHHQ IRU 33*/" +RZ GRHV WKH SUHVHQFH RI ³VSHOOV´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

33

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PL-4

GRAVES’ ORBITOPATHY: AN IMPORTANT ISSUE FOR OPHTHALMOLOGIST AND ENDOCRINOLOGIST T-C CHANG Department of Internal Medicine, National Taiwan University College of Medicine, and National Taiwan University Hospital, Taipei, Taiwan, R.O.C.

Graves' thyroid eye disease which was referred to as Graves' ophthalmopathy, is primarily a disease of the orbit and therefore now called as Graves' orbitopathy. It is an important issue for both ophthalmologist and endocrinologist. Although easily diagnosed by an experienced endocrinologist, it may be treated as conjunctivitis by many doctors. This may result in delaying diagnosis and let the patient progress to irreversible changes or even visual loss due to the compression of the optic nerve. $FWXDOO\ LW FDQ EH GLDJQRVHG E\ WKH FKDUDFWHULVWLF DSSHDUDQFH ZLWK FRQ¿UPDWLRQ E\ RUELWDO FRPSXWHG tomography without contrast medium. In endemic area of HBsAg carrier, check-up of HBsAg before treatment is necessary. If HBsAg is positive, using antiviral agent before pulse therapy can avoid the flare-up of hepatitis B. Pulse therapy with methylprednisolone 250-500 mg depending on the body EXLOGLQJ DQG LQÀDPPDWRU\ VWDWH LQ P/ RI QRUPDO VDOLQH LQWUDYHQRXV GULS IRU DW OHDVW PLQXWHV LQ a consecutive of 3 days every 3 to 4 weeks, totally 6 months, is the effective and cheap way to obtain the therapeutic effect without Cushingoid effect. However, because of excitement may occur after high dose of methylprednisolone infused, patient may have insomnia. Therefore, short-term sedatives before sleep during the days of pulse therapy may be needed. In addition to avoid the smoking, control of thyroid function and wearing goggle during the night are needed. If patient still has diplopia or significant exophthalmos, or impairment of visual acuity after pulse therapy, well-experienced ophthalmologist can further do staged surgery to have better results.

34

Abstract

DAROC-TADE-1

ߞ෉ଢᙺΚঐᇄᢋᑦ‫੿׎‬зхϟԬκᗎ༗ᇅϸ‫ݚ‬ ෇ኋׄ ୾ҴᇄᢋτᏱᚃᏱଲᚃᏱ‫ق‬ϲऌ

Diabetes is a common non-communicable disease that affects hundreds of millions of people ZRUOGZLGH &XUUHQWO\ LW LV WKH ¿IWK OHDGLQJ FDXVH RI GHDWK LQ 7DLZDQ $FFRUGLQJ WR D SURVSHFWLYH IROORZ up of a large cohort of 256,036 diabetes patients for up to 7 years from 1995 to 2001, diabetes patients suffered from a 1.63-fold higher risk of mortality while compared to the general population. However, the cause of death was not ascribed to “diabetes” in more than 70% of the patients. Approximately 48.6% of the patients died of causes probably ascribed to cardiovascular diseases and 18.5% died of cancer. An extension of the follow-up period of a subcohort of 89,056 type 2 diabetes patients who had been interviewed with a structured questionnaire for up to a period of 12 years or to the end of 2016 suggested that the lowest mortality rate was observed in patients with a body mass index within 25 NJ P 7KLV ZDV WKH ¿UVW WR SRLQW RXW WKH H[LVWHQFH RI ³REHVLW\ SDUDGR[´RU D VXUYLYDO DGYDQWDJH in type 2 diabetes patients with mild obesity. A recent follow-up of 92,567 diabetes patients including type 1 and type 2 diabetes until the end of 2011 (up to 17 years) showed that 10.9% of the patients died at an age <60 years. Men with diabetes consistently showed a higher mortality rate than their female counterparts and types of diabetes was not predictive for mortality. Insulin and smoking were consistently predictive for either cancer- or non-cancer-related deaths. However, diabetes duration, hypertension, glycemic control and dyslipidemia were only associated with non-cancer deaths. Patients living in rural areas had a higher risk of mortality than patients living in urbanized areas. Additionally, screen-detected diabetes and obesity provided survival advantage for non-cancer-related deaths.

35

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DAROC-TADE-2

ѯᢋಒ 2 ࠯ᑦ‫੿੿׎‬΢З՗ᆔ੾੿‫ྲޠ‬ៗԚਞ ೩‫ע‬Ԛ ୾ঢ়ፐҢः‫ف‬ଲ

ႇџΡΫԒ‫ٿ‬Ȃѯᢋ‫ޠ‬ᑦ‫ึ੿׎‬Ң౦ᇅ౿՘౦ϛᘟᛈЁȂᗷด‫׫‬ᑦ‫ུޠ੿׎‬᛿ϛᘟึ݃Ȃ ࢈‫ۻ‬ᇅҖ໣ᚃᕜᐡᄻᄈܼᑦ‫੿׎‬ᐍӬྲៗॏฬ (P4P ॏฬ ) ၦྜ‫׺ޠ‬ΤηϛᒹᎸΩȂ௄өᆎྲ ៗࡿዀ‫ࠣޠ‬፵ϸ‫ ( ݚ‬єࢃᑦ‫੿੿׎‬΢௦‫෉ۢڨ‬ᔯࢦ‫ޠ‬Щ౦ණЁȂᐍᡞ௦‫ڨ‬૏৭ષ‫ݾ‬ᕜ‫ޠ‬Щ౦η ቩђȂP4P ॏฬ‫ޠ‬ԚҐਞઊηೞӼ኶Ᏹ޲޼ۢ )ȂѠ࢑ᄈܼᑦ‫੿׎‬ഷ२्‫ޠ‬З՗ᆔ‫઀ึڂ‬ϟྲ ៗԚਞᇅᗎ༗ȂࠔၷЎԥः‫޲ف‬୉‫׈‬ᐍ‫ޠ‬ൣ֚Ȅ ҐԪᅌᗀȂ‫ש‬஡пϸ‫ݚ‬ᐤԒୋߴၦਠ৳࣐лȂ௵ңԇࣁϸ‫࣐ݚ‬л्‫ޠ‬ः‫ف‬Р‫ݳ‬Ȃ௄ࢻ՘੿ Ᏹ‫ِ࡚ޠ‬ᢏᄇᑦ‫੿੿׎‬΢ᑰொЗ՗ᆔ੾੿‫ޠ‬ᐤԒᗎ༗ȂЩၷϸ‫ݚ‬өᆎ‫׫‬ᑦ‫੿׎‬᛿‫ٻޑ‬ң໕ᐤԒ ‫ޠ‬੒ߞ௒‫ם‬Ȃᇅ࢑֐ђΤ P4P ॏฬᄈܼᑦ‫੿׎‬τ՗ᆔ‫ޠ઀ึڂ‬ኈ៫๊Ȃ୉౐Τϟ௥ଇȄҐः‫ف‬ ҭࠊߒؐึ౫Ȃᑦ‫੿੿׎‬΢‫ߣޠ‬༭‫ܓ‬ဟϜॴึҢ౦ԥഃԒ෶Ў‫ޠ‬ᗎ༗ȂѠ࢑я՗‫ܓ‬ဟϜॴึҢ ౦Ս 2003 Ԓϟࡤ൸‫ء‬ԥ᝸៊ί७ȇᑦ‫੿੿׎‬΢‫ޠ‬З᠛૿ᆒึҢ౦η֖ഃԒί७ϟᗎ༗ȂѠ࢑ ЗՋడ༭‫ึޠ‬Ң౦ࠔංо‫ء‬ԥί७ϟᗎ༗ȇᑦ‫੿੿׎‬΢‫ޠ‬Ԭκ౦֖݃ᡘί७ᗎ༗ȂѠ࢑ᄡ޵Щ ౦Ս 2003 Ԓࡤϟί७ᗎ༗ηϛ݃ᡘȇѫѵȂᑦ‫੿੿׎‬΢‫ޠ‬ഇ‫ึݚ‬Ң౦ηծо‫ء‬ԥ‫׾‬๢ၭຬȄ ҐԪᅌᗀ‫ܛ‬ଇ፤‫ޠ‬ԥᜱᑦ‫੿੿׎‬΢З՗ᆔ੾੿ᑰொ౦‫ޠ‬ᗎ༗ϸ‫ݚ‬Ȃϛ༊Ѡпණ‫ٽ‬ຠզᖞ‫ྲט‬ៗ Ԛਞ୥ՄȂη࢑࢈‫ۻ‬൑՞‫ښ‬ॐࣻᜱ࢈๋ਣ‫ޠ‬२्୥Մ‫ٸ‬ᐄȄ

36

Abstract

DAROC-TADE-3

ಒ 1 ࠯ᑦ‫੿׎‬ொ‫ٻ‬ңഀ៊‫ܓ‬՗ᑦᆀข‫ޠ‬ᖞ‫๋ט‬౲ ‫ݔ‬з៤ ᄕϾஆ࿝ఁᚃଲ ϲϸ‫ݫ‬ऌ

In order to optimize the glycemic control, most of the patients with type 1 diabetes need to perform self-monitoring of blood glucose. These glucose profiles sometimes confuse the patients and even the care providers, if they are erratic or in an irregular distribution. Continuous glucose monitoring (CGM), especially the real-time CGM, makes sense for these dilemmas. It has been proved to be effective in reducing glycated hemoglobin level and occurrence of hypoglycemia for type 1 diabetic patients treated with continuous subcutaneous insulin infusion or multiple daily insulin injections. However, the clinical utilities of CGM are still limited. Barriers to clinical implementation, including its reimbursement and the experiences of care providers, should be addressed. Moreover, standardizing the report and analysis of CGM output to optimize clinical decision making is also critical. On March 1st, the health insurance administration had approved reimbursement for retrospective CGM for people with T1DM in Taiwan. There is a need for Diabetes association of Taiwan and Taiwan association of diabetes educators to provide postgraduate training courses for the clinical care providers. The detail will be discussed in the forum.

37

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD1-1

OVERVIEW AND PATHOPHYSIOLOGY OF DIABETIC PERIPHERAL NEUROPATHY MING-HONG CHANG Neurological Institute, Taichung Veterans General Hospital

Objective: To review the prevalence and possibly risk factors for diabetic peripheral neuropathy without pain (DPN) and diabetic peripheral neuropathy with pain (DPNP) in the world and Taiwan Methods: Based on Medical publications concerning DPN and DPNP, we search for the related papers.

Results: We will present the available studies concerning the prevalence of DPN and DPNP and discussing the associated risk factors and possible pathophysiology, including biochemistry and related diseases.

Conclusions: The prevalence of DPN and DPNP is lower among Chinese diabetes patients, as compared with those in Western countries. Biochemical studies for DPN and the risk factors remain controversial and un-certain in pathophysiology; however, we will try to discuss each possible factor causing DPN or worsening the neuropathy.

38

Abstract

SD1-2

TREATMENT OF DIABETIC PERIPHERAL NEUROPATHIC PAIN IN TAIWAN SUN WEI-ZEN Section of Pain Management, Department of Anesthesiology, National Taiwan University Hospital

1. DPN 䘬䕯䉨㱣䗪㗗ẍ pregabalin ㆾ duloxetine Ἦ䶑妋か侭䘬 DPNPˤ 2. TCAs 晾䃞㚱䓐⛐㱣䗪䤆䴻䕭嬲䖃炻Ữ䚖⇵᷎ᶵ㗗⎘䀋堃䤷悐梇喍会㟠⎗䘬 DPNP 喍䈑炻 ἧ䓐㗪ㅱ⮷⽫㲐シ℞㇨⺽䘤䘬∗ἄ䓐ˤ 3. 沱䇯栆喍䈑ᶵ⎗ 䁢㱣䗪 DPNP 䘬䫔ᶨ䶂喍䈑炻⎒㚱䔞䕤䖃䃉㱽塓℞Ṿ䫔ᶨ䶂喍䈑㚱㓰 ㍏⇞㗪炻ㇵ⎗侫ㄖἧ䓐㕤⎰Ἕ㱣䗪ˤ 4. DPN 䘬䕭䎮㱣䗪炻㚱ᶨṃ喍䈑䚖⇵ṵ⛐冐⸲娎槿昶㭝炻Ữ⛐⎘䀋⯂䃉㱽⍾⼿忁ṃ喍䈑 ᷳ㱣䗪ˤ ѯᢋᑦ‫ڻ੿׎‬ᜟઢစ੿ᡑ઄ฯ᛿‫ݾޑ‬ᕜ࡛ឋ

39

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD1-3

DIAGNOSTIC TOOL AND EDUCATION OF DIABETIC PERIPHERAL NEUROPATHY е‫ݾ‬ϰ ѯτᚃଲϲऌഌ

਴ᐄѯᢋӓҖୋஷߴᓏၦਠ৳‫ޠ‬ಜॏၦਠȂѯᢋᑰொᑦ‫ޠ੿׎‬΢πȂϑစົႇ 150 ࿳΢Ȃ Ҧܼߞ෉хᗃѷ።Ȃ‫ཽ܂܂‬գᓎөᆎ‫઀ึڂ‬Ȃኈ៫ಂ࿙ȃ๬᠛ȃઢစ‫ڸ‬З՗ᆔ‫ق‬ಜ๊Ȃ‫ڐ‬ϜȂ ᑦ‫ڻ੿׎‬ᜟઢစ੿ᡑ (Diabetic Peripheral Neuropathy,DPN) ࢑ᑦ‫੿׎‬ளُ‫઀ึڂ‬Ϝ‫ޠ‬ΚᆎȄӶᑦ ‫੿׎‬ொ޲ϜȂᑰொ DPN ‫ޠ‬౿՘౦ȂΚૢഎӶ 30% пαȇঅூ‫ݨ‬ཏ‫࢑ޠ‬Ȃङԥ 20~30% ‫ޠ‬ᑦ‫׎‬ ੿ொ޲ཽӱ࣐‫ڻ‬ᜟઢစ੿ᡑ‫ܛ‬Жึ‫ޠ‬઄ฯ (DiabeticPeripheral Neuropathic Pain, DPNP)ȂՅആԚ ՘୞α‫ޠ‬፞Ӽϛ߰ȂࣦՎᝓ२ኈ៫Ңࣁࠣ፵Ȅ‫ܛ‬ԥᑦ‫੿׎‬ொ޲Ȃഎᔗ௦‫ ڨ‬DPN ᑣᔯȂጃຩᑰ ொಒ 2 ࠯ᑦ‫੿ޠ੿׎‬ொȂሰ्ᅿ‫ץ‬௦‫ ڨ‬DPN ‫ޠ‬ᑣᔯȂጃຩ࣐ಒ 1 ࠯ᑦ‫ޠ੿׎‬ொ޲ȂηᔗӶጃ ຩࡤ 5 Ԓໍ՘ᑣᔯȂԫࡤ҂ְؑԒଢᙺΚԪȄDPN ‫ޠ‬ᖞ‫ט‬ᑣᔯȂሰഇႇᙐܿ‫ޠ‬ᑣᔯ໕ߓ‫ڸ‬ᖞ ‫ט‬དញขၑȂຠզᑦ‫੿׎‬ொ࢑֐‫ڏ‬ԥઢစ੿ᡑ‫ܗޒ઀ޠ‬ኊӑȄଷΠ੿ѭȂDPN ‫ޠ‬ஆҐᑣᔯᔗ єࢃϊઢစᡋᆱᇅτઢစᡋᆱѓ૗‫ޠ‬ขၑȇࠊ޲࣐ᄈྤ࡚‫ܗ‬ଭ‫ޠڗ‬ད‫ޤ‬Ȃࡤ޲࣐ၽң 128Hz ॲ οȂຠզᄈਐ୞‫ޠ‬ད‫ޤ‬Ȅᄈ‫ܛ‬ԥ‫ޠ‬ᑦ‫੿׎‬ொ޲Ȃᚃ৲ؑԒഎᔗп 10 ϵջϟ൑޷ᡋᆱȂຠզ‫ڐ‬ ٘ഌዜᅻᇅᄡ޵‫ॴޠ‬ᓏτϊȄઢစᏱ‫ޠ‬ᆡஞᔯขԥֆܼ DPN ‫ޠ‬ጃຩȂसொ޲֖౫ߩ‫࠯ڑ‬ઢစ ੿ᡑ઀‫ޒ‬ȃຩᘟϛ݃ȃ‫ڐܗ‬уϛӤ‫ޠ‬ԇӶ੿ӱ๊ȂࠍໍΚؐ‫ޠ‬ႬҢ౪ขၑȂ‫ᙾܗ‬ຩ‫ژ‬ઢစϲऌ ԥ‫ܓ्҇ڐ‬Ȅᑦ‫੿੿׎‬ொፐఁӶᐍঐᑦ‫੿׎‬ொ޲‫ྲޠ‬ៗႇโϜȂ࢑࡟२्‫ޠ‬Κഌӌ 48ȄѻଷΠ Ѡпᔔԕᑦ‫੿׎‬ொ޲ӶຩᘟϟߒȂ൸૗໡ۗ୉ԥਞ‫ޠ‬Ս‫៬ྲש‬ѵȂࡼ៊‫ޠܓ‬ᑦ‫੿੿׎‬ொፐఁȂ ᗚ૗ቩໍ՗ᑦ௢‫ښ‬ȂԥਞႲ٪ DPN ๊ᑦ‫ࣻ੿׎‬ᜱ‫઀ึڂ‬Ȃ‫ٯ‬йቩໍ੿΢Ңࣁࠣ፵Ȅ༉ಜ‫ޠ‬ᑦ ‫੿׎‬ፐఁϲৡȂӼၷ୒२ܼԥᜱ‫ޤ‬ᜌпІΚ‫׭ٳ‬Ѿα‫ޠ‬༉௳Ȃ‫پ‬ԄȈ‫ৣݨ‬૏৭ષȃ՗ᑦՍ‫ש‬ᆀ ขȃၽ୞Рԓȃ໾ॶᡞ२௢‫๊ښ‬ȇկߗԒ‫ٿ‬஽።੿΢Ս‫ש‬ᆔ౪ፐఁ (Diabetes Self-Management Education,DSME) ‫܉྆ޠ‬Ȃл्Ӷܼᡲᑦ‫੿׎‬ொ޲Ԛ࣐ᐍঐྲៗႇโϜ‫ޠ‬лِȂӱ࣐ؑ՞੿΢ എԥϛӤҢࣁ࠯ᄙȃНϾनෂȃఁ‫ي‬โ࡚‫ަڸ‬စӵ՞๊Ȃܼ࢑ᚃᕜ஠ཿ΢স ( ‫پ‬ԄȈᚃ৲ȃៗ ౪৲ȃᕋᎵ৲ȃ᛿৲ȃඉୋ৲๊ )Ȃࠍ࢑ᐋӉ੿΢‫ޠ‬Ӏգ‫࢑ܗ‬ЖᏳ޲ِՔȂ‫پ‬Ԅ : ᡲ੿΢л୞ ୥ᇅ‫ۢ؛ٯ‬Ӭᎍ‫ޠ‬ᚃᕜ೏ဋРԓ (SDM)ȂஊᎵՍ‫ש‬၍‫؛‬ୱᚡ૗ΩȂ‫࢑ܗ‬ᡲ੿΢ॐۢಓӬ‫ڐ‬ൊԂȃ Ѡ௦‫ڨ‬ᇅ࡭࿌‫ޠ‬՘୞ҭዀᇅॏฬȇѫѵȂᚃᕜყ໦ηሰ्ϛᘟᇅ੿΢ӔӤᔯຝҭዀ࢑֐ႁԚȂ ‫ڟٯ‬ֆᔯଇȃঔҔ‫ܛڐ‬ॐۢ‫ޠ‬Ս‫ྲש‬ៗҭዀॏฬȄӱԫȂᑦ‫੿׎‬Ս‫ש‬ᆔ౪ፐఁ (DSME)ȂଷΠ ૗஋ቩໍ੿΢ᑦ‫ࣻ੿׎‬ᜱ‫ޤ‬ᜌᇅՍ‫៬ྲש‬՘࣐ȂՅᡞ२ᇅҢࣁࠣ፵ηഎѠ‫׾‬๢Ȅ

40

Abstract

SD2-1

DM COMPLICATION: CV RISK AND EVENT. (MI, STROKE) MING-CHIA HSIEH Diabetes e institute, Changhua Christian Hospital, Taiwan

Patients with diabetes are at higher risk for cardiovascular diseases (CVDs) including myocardial infarction and stroke as compared with non-diabetic people. Cardiovascular diseases also remain the leading cause of morbidities and death in patients with diabetes, highlighting the importance of prevention and treatment of CVDs. Blood pressure control have been proved to reduce CVDs in patients with diabetes. However, the idea goal of blood pressure control remained controversy for diabetes. Statin therapy decreased the risk of CVDs in patients with diabetes.

Glycemic control is the cornerstone of diabetes management. Glucose lowering therapy to reach WKH JRDO VLJQL¿FDQWO\ UHGXFHG PLFURYDVFXODU FRPSOLFDWLRQV HVSHFLDOO\ GLDEHWLF UHQDO GLVHDVH LQ SDWLHQWV with diabetes. The effect of glucose lowering on CVDs by anti-diabetic agents seems to be uncertain.

Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Several randomized controlled trials involving around 60,000 participants have been completed so far and have demonstrated the CV safety of dipeptidyl peptidase 4 inhibitors (saxagliptin, alogliptin and sitagliptin), glucagonlike peptide-1 receptor agonists (lixisenatide, liraglutide and semaglutide) and a sodium-glucose coWUDQVSRUWHU LQKLELWRU HPSDJOLÀR]LQ LQ SDWLHQWV ZLWK W\SH GLDEHWHV $PRQJ WKRVH VWXGLHV OLUDJOXWLGH HPSDJOLÀR]LQ DQG VHPDJOXWLGH VKRZHG VXSHULRULW\ ZLWK DW UHGXFLQJ WKH FRPSRVLWH SULPDU\ HQGSRLQW RI major CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke). In addition, one trial IRXQG DQ LQFUHDVH LQ KHDUW IDLOXUH KRVSLWDOL]DWLRQV ZLWK VD[DJOLSWLQ 7KH ¿QGLQJV RI WKHVH WULDOV PXVW EH compared and contrasted cautiously given the differences in patient populations and trial designs.

Comprehensive CV risk management is important for patients with diabetes. Glycemic control, blood pressure control and lipid lowering could reduce the risk of CVDs. Patients with diabetes are heterogeneous, so patient-centered and individual therapy should be given.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD2-2

TIME FOR NEW FORMS OF INSULIN? CHIA-HUNG LIN Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital

Although a basal–bolus regimen with insulin analogs enables many patients to achieve their glycemic targets, issues associated with variability of action, and an action profile requiring strict administration timing, can reduce the likelihood of attaining good control. Insulin Degludec (IDeg) is an ultra-long acting insulin with a half-life of more than 24 h and a duration of action of more than 42 h. IDeg forms soluble and stable dihexamer in the pharmaceutical formulation with the help of phenol and zinc. IDeg is a once-daily basal insulin that provides a duration of action beyond 42 hours. It is important for people with type 1 and type 2 diabetes to establish a routine for insulin treatment. But for children and adolescents, whose daily routine can vary substantially, the precise injection time is GLI¿FXOW 2Q RFFDVLRQV ZKHQ DGPLQLVWUDWLRQ DW WKH VDPH WLPH RI GD\ LV QRW SRVVLEOH ,'HJ DOORZV IRU ÀH[LELOLW\ LQ GD\ WR GD\ GRVLQJ WLPH ZKHQ QHHGHG $FKLHYHPHQW RI VWHDG\ VWDWH FRQFHQWUDWLRQ KHOSV IDeg to have one-fourth glycemic variability as compared to insulin glargine (IGlar) U100 at steady state concentration. This translates into up to 50% lower risk of hypoglycemia, especially nocturnal hypoglycemia as seen in various clinical trials. Owing to the preserved pharmacokinetic properties of ,'HJ DFURVV SHGLDWULF DQG DGXOW SRSXODWLRQV WKH SRWHQWLDO IRU ÀH[LELOLW\ LQ GRVLQJ WLPH ZKHQ QHHGHG may make IDeg a very useful option for patients and their caregivers.

42

Abstract

SD2-3

INSULIN AND INCRETINS: THE PERFECT PARTNERSHIP? YI-SUN YANG Division chief of endocrinology and metabolism, Chung-Shan Medical University Hospital.

Patients with type 2 diabetes frequently do not reach HbA1c targets. Professional society guidelines recommend initial therapy with metformin, followed by intensification with any of VHYHUDO FODVVHV RI DJHQWV EDVHG RQ DQ DVVHVVPHQW RI HI¿FDF\ K\SRJO\FHPLD ULVN FRQWUDLQGLFDWLRQV cost, and preference. Because of the chronic, progressive nature of type 2 diabetes, many patients require insulin therapy. Basal insulin analogs are recognized as an effective method of achieving and maintaining glycemic control for patients with type 2 diabetes. However, the progressive nature of the disease means that some individuals may require additional ways to maintain their glycemic JRDOV ,QWHQVL¿FDWLRQ LQ WKHVH FLUFXPVWDQFHV KDV WUDGLWLRQDOO\ EHHQ DFKLHYHG E\ WKH DGGLWLRQ RI VKRUW acting insulin to cover postprandial glucose excursions that are not targeted by basal insulin. However, intensive insulin regimens are associated with a higher risk of hypoglycemia and weight gain, which can contribute to a greater burden on patients.

GLP-1 RAs provide multiple potential advantages when combined with insulin. GLP-1 RAs produce robust HbA1c reduction stimulating endogenous insulin secretion and inhibiting the inappropriate postmeal glucagon response in a glucose-dependent manner. These agents have a low hypoglycemia risk as a result. GLP-1 RAs promote weight loss in part through signaling in appetite centers of the hypothalamus. The combination of basal insulin with a glucagon-like peptide-1 (GLP-1) mimetic is a potentially attractive solution to this problem for some patients with type 2 diabetes.

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD2-4

CARDIOVASCULAR OUTCOMES WITH ANTIHYPERGLYCEMIC THERAPY 1,2

KAI-JEN TIEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan

The increased risk of cardiovascular disease in type 2 diabetic patients has been known for decades. However, until recently the cardiovascular (CV) impact of glucose lowering strategies has EHHQ LQDGHTXDWHO\ XQGHUVWRRG 0DMRU FOLQLFDO WULDOV KDYH QRZ LQYHVWLJDWHG WKH LPSDFW RI LQWHQVL¿FDWLRQ of glycemic control upon CV outcomes, as well as the CV effects of glucose management with newer antihyperglycemic agents. Dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) analogs and sodium-glucose cotransporter 2 (SGLT2) inhibitors are relatively new therapies for the treatment of type 2 diabetes mellitus. Given the high prevalence of cardiovascular complications in patients with type 2 diabetes and recent concerns questioning CV safety of newer antidiabetic medications, cardiovascular safety of these medications requires evaluation.

Multiple CV safety trials designed to meet regulatory requirements for CV safety of antihyperglycemic medications have been initiated. The results of several completed CV outcomes WULDOV FODULI\ WKH ULVNV DQG EHQH¿WV DVVRFLDWHG ZLWK QHZHU PHGLFDWLRQV XVHG WR PDQDJH K\SHUJO\FHPLD in patients with type 2 diabetes, particularly in individuals at high CV risk. Important differences have been noted with respect to heart failure outcomes within the DPP4 inhibitor class, and thus far RQH DJHQW LQ WKH 6*/7 LQKLELWRU FODVV KDV EHHQ IRXQG WR VLJQL¿FDQWO\ UHGXFH UDWHV RI LPSRUWDQW &9 outcomes. Robust safety related information from trials designed to assess the CV effects of diabetes therapies will permit the incorporation of outcomes-based evidence into the formulation of diabetes care guidelines.

Based on review of the present evidence, these 3 classes of antihyperglycemic therapies have DFFHSWDEO\ VDIH &9 VDIHW\ SUR¿OHV IRU SDWLHQWV ZLWK W\SH GLDEHWHV 7KH ODWHVW HYLGHQFH IURP /($'(5 and EMPA-REG OUTCOME trials indicate that liraglutide and empagliflozin have cardiovascular EHQH¿WV WKDW PD\ SURYH WR EH RI FOLQLFDO LPSRUWDQFH LQ WKH PDQDJHPHQW RI W\SH '0

44

Abstract

SD2-5

WHAT’S NEW FROM UPDATED TREATMENT ALGORITHM? MEI-YUEH LEE Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang 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 .Department of Medicine, Kaohsiung Medical University, Taiwan, R.O.C.

The goals in caring for patients with diabetes mellitus are to eliminate symptoms and to prevent, or at least slow, the development of complications. Microvascular (ie, eye and kidney disease) risk reduction is accomplished through control of glycemia and blood pressure; macrovascular (ie, coronary, cerebrovascular, peripheral vascular) risk reduction, through control of lipids and hypertension, smoking cessation, and aspirin therapy; and metabolic and neurologic risk reduction, through control of glycemia.Type 2 diabetes care is best provided by a multidisciplinary team of health professionals with expertise in diabetes, working in collaboration with the patient and family. Management includes WKH IROORZLQJ DSSURSULDWH JRDO VHWWLQJ GLHWDU\ DQG H[HUFLVH PRGL¿FDWLRQV PHGLFDWLRQV DSSURSULDWH self-monitoring of blood glucose (SMBG), regular monitoring for complications and laboratory assessment. Ideally, blood glucose should be maintained at near-normal levels (preprandial levels of 90-130 mg/dL and hemoglobin A1C [HbA1c] levels < 7%). However, focus on glucose alone does not provide adequate treatment for patients with diabetes mellitus. Treatment involves multiple goals (ie, glycemia, lipids, blood pressure).Early initiation of pharmacologic therapy is associated with improved glycemic control and reduced long-term complications in type 2 diabetes. Drug classes used for the treatment of type 2 diabetes include the following: biguanides, sulfonylureas, meglitinide derivatives, alpha-glucosidase inhibitors, thiazolidinediones (TZDs), glucagonlike peptide–1 (GLP-1) agonists, dipeptidyl peptidase IV (DPP-4) inhibitors, selective sodium-glucose transporter-2 (SGLT-2) inhibitor, insulins, amylinomimetics, bile acid sequestrants, and dopamine agonists.

Recommendations for the treatment of type 2 diabetes mellitus from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) place the patient's condition, desires, abilities, and tolerances at the center of the decision-making process. The EASD/ ADA position statement contains 7 key points: 1. Individualized glycemic targets and glucose-lowering therapies 2. Diet, exercise, and education as the foundation of the treatment program 8VH RI PHWIRUPLQ DV WKH RSWLPDO ¿UVW OLQH GUXJ XQOHVV FRQWUDLQGLFDWHG 4. After metformin, the use of 1 or 2 additional oral or injectable agents, with a goal of minimizing adverse effects if possible 5. Ultimately, insulin therapy alone or with other agents if needed to maintain blood glucose control 6. Where possible, all treatment decisions should involve the patient, with a focus on patient preferences, needs, and values 7. A major focus on comprehensive cardiovascular risk reduction 45

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD2-6

GESTATIONAL DIABETES MANAGEMENT AND NICE GUIDELINE RECOMMENDATION ANNE DORNHORST, M.D., Consultant Physician & Professor of Practice Imperial College London; Department of Medicine; Imperial College Healthcare NHS Trust

Pregnancy is associated with temporary changes in maternal metabolism which include a decrease in maternal fasting glucose concentrations as gestation progresses and an increase in postprandial glucose concentration as tissue sensitivity to insulin decreases. The maintenance of glucose tolerance in pregnancy requires a two- to three-fold increase in postprandial maternal insulin secretion by the beta-cells. Glucose intolerance develops in women unable to compensate for the metabolic changes associated with pregnancy. Gestational diabetes tends to occur from the 24th week of pregnancy.

2YHUW V\PSWRPV RI K\SHUJO\FDHPLD GXULQJ SUHJQDQF\ DUH UDUH DQG GLI¿FXOW WR GLVWLQJXLVK IURP QRUPDO pregnancy symptoms, but may include increased thirst and frequent urination. Risk factors for GDM include advanced maternal age, obesity, family history (in particular maternal history) and non-white racial/ethnic origin. Physical activity is regarded as a protective factor and may delay or prevent the development of GDM and prevent complications to the foetus. In most cases of gestational diabetes, blood glucose levels can be controlled through a healthy diet, gentle exercise and blood glucose monitoring. In some cases, insulin or oral medication may also be prescribed. Gestational diabetes normally disappears after giving birth. However, women who have been previously diagnosed with GDM are at higher risk of developing GDM in subsequent pregnancies and T2DM later in life. Babies born to mothers with gestational diabetes also have a higher risk of developing T2DM in their teens or early adulthood.

46

Abstract

SD3-1

TAIWAN DIABETES REGISTRY STUDY: AN INTRODUCTION AND PRELIMINARY REPORT ‫ݔ‬ਣ໌ ᇄϜᄹҖᖃᚃଲାឮᚃᏱϜЗ

Despite a great efforts and advocates been introduced and implemented in promoting diabetes care, many diabetes patients are remained suboptimal controls. In Taiwan, two surveys in 2006 and 2011 commissioned by the Bureau of Health Promotion, Department of Health, ROC (Taiwan), and the Taiwanese Association of Diabetes Educators (TADE) showed that target achievement with respect to glucose, blood pressure and lipid control in diabetic patients were still suboptimal. In several countries and areas, including Sweden, Denmark, Australia, and Hong Kong, national diabetes registers are established as part of a quality improvement program of diabetes care. It has been shown by several studies that diabetes registry projects can help several issues in diabetes managements, including survey of epidemiology, and genetics, clinical presentations, diabetic and its related and associated complications, medication administration, and long term outcome. To further understand the care conditions in the patients with diabetes in this country, the Diabetes Association of R.O.C. (Taiwan) launched the Taiwan Diabetes Registry Study since 2015, October. This study is an observational study without additional intervention, and approved by join IRB in Taiwan. It will continuously enroll diabetic patients from 2015, Oct 1 to 2018, Jun 30, and follow period will be end until 2018, Dec 31.

The diabetic patients ever enrolled into the quality control study by Taiwan Association of Diabetes Educators in 2006 and 2011, type 1 diabetic patients , and newly diagnosed type 2 diabetic patients are to be recruited. After obtaining the signed informed consent forms, the clinical information and various disease-related medical records of the patients are registered on the network. Then, at least one annual follow-up information will be re-registered yearly until 2018. In the web-based platform of Taiwan Diabetes Registry Study, the personal information (height, weight, blood pressure, waist and hip circumference, family history and history of cardiovascular disease), living habits (smoking, drinking, diet and activity level), the lab tests (lipids, blood glucose, HbA1c, renal and liver function), foot assessment, macrovascular and microvascular complications of diabetes, self-management status, and hospital admission history, etc., are recorded. In each registration, the patients also require completion of some questionnaires, such as Patient Health Questionnaire (PHQ-9), EQ-5D, etc. In this study, at present, a total of 95 diabetes health promotion institutes have given their permit to participate the diabetes registry study. Among them, 26 sites are distributed in north Taiwan, 48 in central Taiwan, 18 in south Taiwan and 3 in east Taiwan. Until Sep 30, 2016, a total of 2728 diabetic patients, including 847 who previously participated the quality control study by Taiwan Association of Diabetes Educators in 2006 and 2011, 595 type 1 diabetic patients , and 1286 newly diagnosed type 2 diabetic patients had been enrolled. For the 847 patients (aged 66.9 r 11.3 yrs; male 50.6% ) who previously participated the quality control study by Taiwan Association of Diabetes Educators in 2006 and 2011, 32.2% of patients had an A1c value less than 7%, 63.2% with a LDL-C level less than 100mg/dL, 30.4% with 47

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

a BP less than 130/80mmHg. For the newly diagnosed type 2 diabetic patients (aged 54.0 r 13.7 yrs; male 57.4%), 36% of patients had an A1c value less than 7%, 44% of with a LDL-C level less than 100mg/dL, 66.6% of patients had a BP less than 140/90mmHg. It is hoped that the rich dataset of Taiwan Diabetes Registry Study will provide an opportunity to address numerous issues of relevance to clinicians and patients, including assessments of associations between patient characteristics and diabetes management factors with outcomes.

48

Abstract

SD3-2

BIOBANK IN REGISTRY STUDY CHEN-YANG SHEN, FU-TONG LIU Taiwan Biobank, Academia Sinica, Taiwan

The Taiwan Biobank (TWB) is establishing a scientific infrastructure that is accessible to biomedical researchers to increase our understanding of the relationships among genetics, environment, diet, and the etiology/progression of diseases. This effort is based on the recruitment and monitoring of a cohort of 200,000 individuals from the general Taiwanese population with no history of cancer and another 100,000 patients with chronic diseases of public health importance. TWB aims to improve the health of future generations and facilitate genomic research in Taiwan. The progressive elucidation of risk factors and of the molecular pathogenesis of disease will both improve disease prevention and facilitate the development of individualized prevention and therapy. Currently, more than 80,000 participants have been recruited, and >1,800,000 tubes of specimens have been collected. Staring from Sep, 2014, TWB has released both information and specimen to the public, and more than 100 studies have applied for these for in-depth research. In addition to the ongoing establishment of recruitment centers throughout Taiwan, TWB is currently focusing on disease gene mapping. A populationspecific reference of whole-genome genotyping, more than 20,000 whole-genome genotypings and ZKROH JHQRPH VHTXHQFHV KDYH EHHQ FRPSOHWHG 7R WKH EHVW RI RXU NQRZOHGJH 7:% LV WKH ¿UVW and largest publically available Asian reference cohort. Through this study, the TWB has released the largest genome-wide genotype statistics for Han Chinese, providing appropriate statistical power to detect susceptibility variants, and the publicly accessible web-based calculation platform, Taiwan View, has been built to carry out genetic study using current control data.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD3-3

PRECISION MEDICINE USING REGISTRY DATA U-C YANG Institute of Biomedical Informatics, National Yang-Ming University, Taiwan, R.O.C.

OBJECTIVE Most diseases have different subtypes. Different subtypes may have different responses to the same treatment. Therefore, it is important to identify the subtypes and give the right treatment for a given subtype. Precision medicine aims to classify diseases into subtypes based on a biomarker or a group of biomarkers (i.e. a bio-signature). To reach this goal, it is essential to integrate all types of information into a knowledge network. Data mining approaches can then be used to identify candidate bio-signatures for further studies.

MATERIAL AND METHODS The clinical informatics and management system (CIMS) has 4 subsystems, in which 3 of them have been used to establish a disease registry. The Clinical Study Information System (CSIS) can be used to collect clinical information; the Specimen Tracking and Management System (STAMS) can be used to record the storage location; the Global Unique IDentifier (GUID) can be used to integrate the clinical information and the high throughput data derived from bio-specimens. Both CSIS and STAMS can be deployed in a single sign-on portal. In other words, registry manager may switch between CSIS and STAMS without further login in this portal environment.

RESULTS The clinical and microarray data of breast cancer obtained from public repository were used to mimic a disease registry. The clinical data were stored in CSIS and the early phase study subjects can be selected by querying the CSIS. The microarray data of these patients were retrieved and normalized to one another. A gene expression threshold was optimized for each gene in order to separate patients into high and low expression groups, respectively. Those genes, which have a significant survival difference between the high and low expression groups, were identified as candidate biomarkers. Some of the pair-wise combination of these candidate biomarkers showed synergistic effects. In other words, such gene pairs can be used to identify a group of patients that have a poor 5-year survival rates.

CONCLUSIONS Gene expression bio-signatures can be used to classify a disease into subgroups.

The functions of these genes may lead to the discovery of a disease mechanism. Such mechanism is the basis to translate genomic observation into a therapeutic treatment. If a treatment of the most severe subgroup can be found, the bio-signature becomes a companion biomarker for this particular disease subgroup. Taken together, companion biomarker makes disease diagnosis and treatment more SUHFLVH 7KLV LV WKH ¿UVW VWHS WRZDUG WKH JRDO RI SHUVRQDOL]HG PHGLFLQH

50

Abstract

SD4-1

AN UPDATE ON DIABETES KIDNEY DISEASE PROFESSOR WASIM HANIF MBBS, MD, FRCP Professor of Diabetes & Endocrinology University Hospital Birmingham UK

OBJECTIVE Diabetes Nephropathy affects up to 40% of diabetes individuals this lecture is a scholastic update of this area. It covers the following: :KDW LV 'LDEHWHV .LGQH\ 'LVHDVH" 3DWKRJHQHVLV DQG SURJUHVVLRQ 'LVFXVV ULVN IDFWRUV 7KH FKDOOHQJHV RI DVVHVVPHQW DQG PDQDJHPHQW RI WKH 'LDEHWHV .LGQH\ 'LVHDVH LQFOXGLQJ WKH dose adjustments with medications (PHUJLQJ DQG 1HZ WKHUDSLHV IRU 'LDEHWHV .LGQH\ 'LVHDVH The various sections are presented in details with up to date evidence to comprehensively cover this challenging area. The challenges of managing DKD both in terms of diabetes and other related issues are discussed with supporting evidence.

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD4-2

DIABETES MELLITUS AND DEMENTIA 1,2,3

Y-H, YANG

1

Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Master’s Program in Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

A growing body of clinical and epidemiological research suggests that two of the most common diseases of aging, type 2 diabetes (T2DM) and Alzheimer disease (AD), are linked. This linkage may be appreciated with some prevalence studies.

Over the last 25 years, many countries have seen in- creases in obesity, T2DM, and hypertension, all of which have been linked to an increase in dementia risk. However, at the same time, there have been important changes in treatments for these cardiovascular risk factors, including more widespread and intensive medication treatments These improvements in cardiovascular risk factor control have helped cut these disease related complications and have likely the important ‘spillover’ benefits for brain health and the risk for cognitive decline and dementia during controlling these risk factors through drug and non-drug treatments.

AD, the most common cause of dementia, is a progressive and fatal neurodegenerative disorder in which certain types of neurons in particular brain regions degenerate, resulting in severe neuronal ORVV $' LV FKDUDFWHUL]HG E\ WZR PDMRU SDWKRORJLFDO KDOOPDUNV VHQLOH SODTXHV 63V DQG QHXUR¿EULOODU\ tangles (NFTs). This advancing pathology is believed to underlie the clinical presentation of memory GH¿FLHQF\ ¿UVW IROORZHG E\ WKH VWHDG\ ORVV RI MXGJHPHQW YHUEDO ÀXHQF\ UHDVRQLQJ VNLOOV DQG RWKHU cognitive functions. SPs are the extracellular deposition of aggregated beta -amyloid protein in the FRUWLFHV RI $' SDWLHQWV¶ EUDLQV DQG VXFK FKDQJHV ZLOO LQGXFH LQÀDPPDWRU\ UHVSRQVHV YLD DVWURJOLDO DQG microglial activation to these unwanted outcomes.

T2DM is thought to arise in its earliest stage from decreased sensitivity of peripheral tissues to circulating insulin, leading to impaired glucose tolerance, compensatory hyperinsulinemia in an DWWHPSW WR PDLQWDLQ JOXFRVH KRPHRVWDVLV DQG UHODWLYH LQVXOLQ LQVXI¿FLHQF\ 7KDW DQ DQDORJRXV SURFHVV of cellular insulin resistance and insulin insufficiency is occurring in the brain in AD is becoming evident, including in those without systemic diabetes, and for this reason some have referred to AD as “ type 3 diabetes.

Recent advances in the understanding of the biology of T2DM have resulted in a growing number of therapies that are approved or in clinical development for this disease. During the talk, beyond review the possible mechanisms between T2DM and AD, I am going to assesses the various diabetes drugs for their potential activity in AD to determine their value for AD in general.

52

Abstract

SD5-1

CURRENT STATUS OF DIABETIC FOOT CARE IN TAIWAN AND TREATMENT OF INFECTION ༂ऊ൞ ‫ݔ‬πߞ۹ख‫܉‬ᚃଲϲϸ‫ུݫ‬ചхᗃऌІᕋᎵ‫ݾ‬ᕜऌ

‫ٸ‬ୋߴၦਠ৳ȂӶѯᢋؑԒङԥ 1% ᑦ‫੿੿׎‬ொӱᝓ२ᑦ‫٘੿׎‬՟ଲ‫ݾ‬ᕜȂՅᄡ޵౦ାႁ ήԚȄ೼ᇅज୾ᑦ‫ؑ੿׎‬Ԓԥ 3.2‰ ੿΢ᄡ޵‫ޠ‬Щ‫ߗࣻپ‬Ȅ‫޲ࣦ؂‬ΚҎ੿΢ึҢᑦ‫٘੿׎‬ዜᅻȂ ‫ڐ‬҂ְԇࣁਣ໣༊ 6.14 ԒȂՅ௦‫ڨ‬ᄡ޵ொ޲༊ԥ 3.25 ԒȄӱԫȂԄեႲ٪ȃԄեߴ޵ࣲ࢑२ ्፟ᚡȄ ङ 80% ᑦ‫੿੿׎‬΢ᄡ޵କྜܼ٘ഌዜᅻȂॴᓏӱφєࢃᑦ‫੿׎‬ઢစ੿ᡑȃᑦ‫ڻ੿׎‬ᜟ՗ ᆔ੾੿ȃ٘ഌᡑ‫ם‬ȃ٘ഌ‫ڨ‬Ω‫׾‬ᡑȃຝΩϛ‫ٺ‬ȃ٘ഌѵ།ȄΚҎዜᅻึ৥ඍϾȂ٘ഌད࢘І‫ڻ‬ ᜟ՗ᆔ੾੿࣐ᄡ޵л्‫ޠ‬ӱφȄӱԫȂΚҎ੿΢ึҢᑦ‫٘੿׎‬ዜᅻ՟ଲȂ‫ݾ‬ᕜளሰᐍӬϲऌᄈ хᗃᇅད࢘‫ޠ‬௢‫ښ‬ȃ՗ᆔऌᄈܼ‫ڻ‬ᜟ՗ᆔ‫ޠ‬ຩᘟᇅ‫ݾ‬ᕜȃѵऌ‫ޠق‬К೛ఽ഻Жࢻ‫ܗ‬ᄡ޵ෛҫȃ ඉୋऌ‫ޠ‬෶ᔇ๊Ȅ ӶϜ๽Җ୾ᑦ‫੿׎‬Ᏹཽ೩౪‫ޠߞٲ‬τΩМࡼίȂ‫ש‬উ๗ӬҐཽ஠ঢ়Ȃ‫ٯ‬ᗝ፝өࣻᜱስ஀Ᏹ ཽ୥ᇅȄӶԫ‫्ש‬੬րདᗃᐍ‫ם‬ѵऌᚃᏱ଼ཽԢ౪‫ߞٲ‬ȃඉୋᚃᏱཽе߫ີ౪‫ߞٲ‬ȃЗ᠛Ᏹཽ ဩීࢹ౪‫ߞٲ‬ȃϮΤ‫ܓ‬З᠛՗ᆔᚃᏱཽ࣓֕ϧ౪‫ߞٲ‬ȃଽऌᚃᏱཽૅН૗౪‫ߞٲ‬Іᑦ‫੿׎‬ፐఁ Ᏹཽ؈ࡧ኉౪‫ߞٲ‬ȂዦЗࡿࣃ஠ঢ়୥ᇅȂ෉ࣿ૗Ӷҭࠊ୾ϲᚃᕜ࢝ᄻίණ‫୾ٽ‬΢‫׈؂‬๢йԥਞ ઊ‫ޠ‬ᑦ‫ྲ٘੿׎‬ៗȄѯᢋᑦ‫٘੿׎‬ϏձϊಣܼౚԚҴȄ ܼ 2016 Ԓ 5 У 30 СಒΚԪϏձϊಣཽឋϜឋ‫؛‬ಒΚঐϏձӉଡ଼࣐ѯᢋᑦ‫ྲ٘੿׎‬ៗྦ ࠍ‫ޠ‬ኦቹȄߩளདᗃჲգউ‫ޠ‬ณ‫ۉؾ‬ᝧᇅყ໦ӬձȂҐྲៗྦࠍூпӶԥ४‫ޠ‬ਣ໣ϲ‫׈‬ԚȄ ‫ש‬উ୥Մ୾ϲୋߴၦਠȂп୾΢ᑦ‫٘੿׎‬ၦਠึߓϟᏱ೛፤НȂђα୾ርαߗԒึߓϟᑦ‫׎‬ ੿٘‫ݾ‬ᕜࡿЖԄ IWGDF 2015 Ԓ guidanceȂज୾ Society for Vascular SurgeryȃPodiatric Medical Association І Society for Vascular Medicine 2016 ӔӤึߓϟ practice guidelineȃAmerican Heart Association ᇅ American College of Cardiology 2016 ึߓϟ Lower Extremity PAD guidelineȂ‫ٸ‬ө ஠ऌӶ୾ϲᄈᑦ‫ޠ٘੿׎‬ᖞ‫ט‬ၽձȂቹяҐ‫ྲޠޏ‬ៗྦࠍȄഌϸ‫ݾ‬ᕜҦܼۧુн٘஋ः‫ف‬ᜍᐄ ӱԫϛӗΤҐ‫ྲޏ‬ៗྦࠍ࡛ឋϜȄ࣐ؒབྷ२Ȃ‫ש‬উ‫ ܼٯ‬2016 Ԓ‫ܼۼ‬ϲऌᚃᏱཽԒཽϜᖟᒳӔ ᜌཽឋȂໍ՘ߒጉ‫ߓึޠ‬І൷ؒ୾ϲ஠ঢ়উ‫࡛ޠ‬ឋȄ෉ࡠᙥҦԫᑦ‫ྲ٘੿׎‬ៗྦࠍ૗ԥਞᐍӬ ୾ϲྲៗၦྜȂ෶Ўᄡ޵Ȃпණ݈‫ݾ‬ᕜᇅ٪‫ޠݾ‬ਞઊȄ Ӷ‫ݾ‬ᕜᝓ२٘ഌዜᅻਣȂցᘟᑦ‫٘੿׎‬ད࢘Іϸ઼࣐ॷ्Ӊଡ଼ϟΚȄሰପӬ‫ڻ‬ᜟ՗ᆔຠ զឍབྷᒶᐆ‫׫‬Ңષᇅኵਠ‫ٯ‬ᎍਣ‫ޠ‬ѵऌఽዷȄ‫ש‬উཽᄈܼᑦ‫٘੿׎‬ད࢘‫ٸ‬ϸ઼ȃຠզȃཌྷҢ ‫ޑ‬ᔯขȃኈ჌ᔯࢦȃଽᡝ‫ވ‬ȃѵऌ೏౪ȃ‫׫‬Ңષ‫ݾ‬ᕜІ‫ڐ‬уህֆ‫ݾ‬ᕜӶࡿЖϜ‫ޠ‬२ᘉၐಡϸ ‫ݚ‬ൣ֚Ȅ

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD5-2

PERIPHERAL ARTERY DISEASE MANAGEMENT IN PATIENTS WITH DIABETIC FOOT ULCER WEI-KUNG MD, PHD Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan, Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, Taiwan

Diabetes is strongly associated with the presence of peripheral artery disease (PAD). PAD is not only an independent risk factor for developing foot ulceration and amputation, it is also associated with a higher risk of cardiovascular disease and overall mortality. Therefore it is important to diagnose PAD promptly and accurately, and to take steps to minimize its deleterious effects.

The diagnosis of PAD is challenging in patients with diabetes. Medical history and physical H[DPLQDWLRQ ¿QGLQJV IRU WKH GHWHFWLRQ RI 3$' DUH RI OLPLWHG XVH LQ GLDEHWHV 3HULSKHUDO QHXURSDWK\ may mask symptom of PAD. Co-exist arteriosclerosis, edema and infection make clinical assessment IRU 3$' GLI¿FXOW %XW LW LV VWLOO UHFRPPHQGHG DQQXDOO\ FKHFN XS IRU WKH SUHVHQFH RI 3$' LQFOXGH DW D minimum, taking a history and palpating foot pulses. For patients with diabetes and foot ulcer, further non-invasive tests should be arranged for determine the presence of PAD. 7KHUH LV QRW VXI¿FLHQW HYLGHQFH WR VXSSRUW D VLQJOH EHGVLGH QRQ LQYDVLYH GLDJQRVWLF PRGDOLW\ IRU the detection of PAD across a spectrum of patients with diabetes. Non-invasive tests for the detection of PAD among individuals with diabetes are important to estimate the risk of amputation, ulceration, wound healing and presence of cardiovascular disease. Ankle brachial index (ABI) is the most widely used for screening of PAD, with exclusion of PAD at value 0.9 - 1.3. Alternative toe brachial index (TBI) <0.75 and Doppler wave form analysis could be other screening tests for PAD. ,Q SDWLHQWV ZLWK D IRRW XOFHU LQ GLDEHWHV DQG 3$' QR VSHFL¿F V\PSWRPV RU VLJQV RI 3$' UHOLDEO\ predict healing of the ulcer. Diabetic microangiopathy should not be assumed to be the cause of poor wound healing in patients with a foot ulcer. Consider urgent vascular imaging and revascularization in a patient with toe pressure <30 mmHg, ankle pressure <50 mmHg, ABI < 0.5 and ulcer does not improve within 6 weeks despite optimal management.

Vascular image include color duplex ultrasound, computed tomography angiography, magnetic resonance angiography or intraarterial digital subtraction angiography to obtain anatomical information when revascularization is being considered. Revascularization can be performed either by endovascular techniques or surgical bypass. There is inadequate evidence to establish which revascularization technique is superior, and decisions should be made LQGLYLGXDOL]HG 7KH DLP RI UHYDVFXODUL]DWLRQ LV WR UHVWRUH GLUHFW ÀRZ WR DW OHDVW RQH RI WKH IRRW arteries, preferably the artery that supplies the anatomical region (angiosome) of the wound. After 54

Abstract

revascularization procedure, patient should be treated by multi-disciplinary and comprehensive program. Patients with signs of PAD and a foot infection (critical limb ischemia, CLI) are at particularly high risk for major limb amputation and require urgent treatment. All patients with diabetes and an ischemic foot ulcer should receive aggressive cardiovascular risk management, including risk factors control, antiplatelet and statin.

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD5-3

DIABETIC FOOT WOUND HEALING AND SURGICAL TREATMENT CHERNG-KANG PERNG M.D., PH.D. Division of Plastic and Reconstruction Surgery, Department of Surgery, Taipei Veterans General Hospital

The treatment of diabetic foot ulcers is still a major challenge in clinical practice. There is still a lot of uncertainty about the choice of best treatment. Since 2008, the International Diabetes Foot Working Group (IWGDF) has conducted a number of systematic review on the topic of wound healing, for clarifying the evidence of the routine care program efficacy, and further analyzing the effect of interventional treatment for improving chronic ulcer healing reported in literature.

At present, the interventional treatment of chronic ulcer can be divided into the following ten categories: sharp debridement and wound bed preparation with larvae or hydrotherapy; wound bed preparation using antiseptics, applications and dressing products; resection of the chronic wound; oxygen and other gases, compression or negative pressure therapy; products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; application of cells, including platelets and stem cells; bioengineered skin and skin grafts; electrical, HOHFWURPDJQHWLF ODVHUV VKRFNZDYHV DQG XOWUDVRXQG DQG RWKHU V\VWHPLF WKHUDSLHV ZKLFK GLG QRW ¿W LQ the above categories.

Despite there are currently considerable number of treatment methods for diabetic foot and chronic ulcers, and new methods also been developed, the effectiveness of diabetic foot treatment is still a challenge. The cost and benefit of new treatments must be thoroughly studied and analyzed.

From the evidence of the current literature, most of the current treatment for chronic wounds are lack of strong evidence support. We will review the current approach to the treatment of diabetic foot and chronic ulcer in Taiwan, and put forward our recommendations and guidelines.

56

Abstract

SD5-4

OFFLOADING AND PREVENTION OF DIABETIC FOOT ULCER 1,2

C-K CHEN

1

Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C. College of Medicine, Chang Gung University, Taiwan, R.O.C.

2

To prevent diabetic foot ulcer, a wide variety of interventions have been used in clinical practice.

7KH IXQGDPHQWDO HOHPHQWV IRU VXFFHVVIXO SUHYHQWLRQ RI GLDEHWLF IRRW XOFHU LQFOXGH LGHQWL¿FDWLRQ RI the at-risk foot by annual screening for signs and symptoms of peripheral neuropathy and peripheral artery disease; (2) regular inspection and examination of the feet and footwear/socks, especially in high-risk diabetics patients; (3) education of patient, family and healthcare providers about preventive foot care in an organized, structured and repeated manner; (4) routine wearing of properly fitting footwear to prevent a first foot ulcer, either plantar or non-plantar, or a recurrent non-plantar foot ulcer, both indoors and outdoors; and (5) treatment of any pre-ulcerative sign on the foot until the preulcerative sign resolves and not recur over time.

In addition, offloading plays an important role in preventing and healing diabetic foot ulcers.

The commonly used offloading techniques consist of casting and prefabricated healing devices, WKHUDSHXWLF IRRWZHDU VXUJHU\ DQG RWKHU RIÀRDGLQJ LQWHUYHQWLRQV 7KH VWUHQJWK RI HYLGHQFH DQG OHYHO RI UHFRPPHQGDWLRQ IRU WKHVH RIÀRDGLQJ WHFKQLTXHV ZLOO EH VXPPDUL]HG KHUH

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE1-1

CUSHING’S SYNDROME: UPDATE AND REVIEW ചో਷ ᇄіᄹҖᖃᚃଲϲऌഌϲϸ‫ݫ‬ᄳུചхᗃऌ

&XVKLQJ¶V V\QGURPH ¿UVW GHVFULEHG E\ +DUYH\ &XVKLQJ LQ DQG LV D JURXS RI GLVHDVHV due to prolonged exposure to cortisol. Signs and symptoms may include abdominal obesity with thin arms and legs, a round red face, a fat lump between the shoulders, purplish stretch marks (striae), acne, fragile skin with heals poorly, muscles weakness, osteoporosis and high blood pressure. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

Cushing’s syndrome is generally considered a rare disease. It occurs an incidence of 0·2–5·0 per million people per year with a prevalence of 39–79 per million in various populations. However, a mild degree of overproduction of cortisol without obvious symptoms is more common. Endogenous Cushing’s syndrome is divided between ACTH-dependent (about 80%) and ACTH-independent (about 20%) causes. Among ACTH-dependent forms, pituitary corticotroph adenoma (Cushing’s disease) is the most common, followed by ectopic ACTH syndrome, and CRH syndrome is rare. Cortisol excess from primary unilateral adrenal adenomas or carcinomas suppresses ACTH. Rarely, Cushing’s syndrome is caused by primary bilateral macronodular adrenal hyperplasia (BMAH), ACTHindependent macronodular adrenal hyperplasia (AIMAH) or primary pigmented nodular adrenocortical disease (PPNAD) and its non-pigmented variant, isolated micronodular adrenocortical disease.

'LDJQRVLV UHTXLUHV D QXPEHU RI VWHSV 7KH ¿UVW VWHS LV WR FKHFN WKH PHGLFDWLRQV D SHUVRQ WDNHV The second step is screening and confirmation of diagnosis: 24 h urine free cortisol (UFC), the 1 mg overnight (or two-day, 2 mg) dexamethasone suppression test, and late night salivary cortisol are recommended. To optimize sensitivity, guidelines recommend using the upper limit of the UHIHUHQFH UDQJH IRU 8)& DQG VDOLYDU\ FRUWLVRO DQG D FRUWLVRO FRQFHQWUDWLRQ OHVV WKDQ ā ȝJ G/ DIWHU dexamethasone as the cut-off for healthy responses. Patients with two abnormal screening test results can be diagnosed with Cushing’s syndrome. Once Cushing’s syndrome is diagnosed, the cause should EH LGHQWL¿HG WR GHWHUPLQH D VSHFL¿F WUHDWPHQW 7KH QH[W VWHS LQ WKH GLIIHUHQWLDO GLDJQRVLV RI &XVKLQJ¶V syndrome is measurement of plasma ACTH. A decreased plasma ACTH concentration in a patient usually suggests an adrenal cause and CT scan for adrenal gland is necessary. For ACTH-dependent Cushing’s syndrome, MRI of pituitary is the investigation of choice. If the differentiated diagnostic testing is ectopic ACTH syndrome, further image should include high-resolution CT scanning of the chest and abdomen.

58

Abstract

SE1-2

MEDICAL MANAGEMENT OF CUSHING'S SYNDROME HUNG-YU CHANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan, R.O.C.

The main indications for medical therapy of Cushing's syndrome(CS) are (1) when surgery being contraindicated, (2) control of hypercortisolism in preparation for surgery, (3) persistence or recurrence of hypercortisolism after surgery, (4) control of hypercortisolism while waiting for the effect of pituitary radiation in patients with Cushing's disease(CD), and (5) treatment of occult ectopic ACTH syndrome. Ketoconazole and metyrapone have been the most frequently used medical therapies for CS. Ketoconazole has been used worldwide for more than 30 years in CS. A retrospective ketoconazole study comprising 200 patients with CD showed that almost 50% of patients who continued on ketoconazole therapy achieved biochemical control and clinical improvement and 20.5% of patients stopped the treatment due to poor tolerance. Metyrapone is a pharmacologic agent used LQ WKH GLDJQRVLV RI DGUHQDO LQVXI¿FLHQF\ DQG RFFDVLRQDOO\ LQ WKH WUHDWPHQW RI &6 ,Q D UHWURVSHFWLYH survey including 195 patients with CS, metyrapone therapy achieved a control rate ranged between 43 and 76% in reference to different criteria of biochemical control. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness. Fluconazole inhibited 11-deoxycortisol and cortisol production. There are few reports of fluconazole use in CS patients. Mitotane is an antineoplastic agent used in the treatment of adrenocortical carcinoma but also rarely used to treat CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects, could control hypercortisolism in the majority of CD patients. Etomidate is the only drug available for intravenous use and a significant suppression of serum cortisol levels occurs after 5 hours. As a glucocorticoid receptor blocker, Mifepristone acts directly at the cortisol glucocorticoid receptor and the progesterone receptor. The US FDA approved mifepristone for the treatment of hyperglycemia associated with CS in 2012. The D2-receptor agonist cabergoline, induces long-term biochemical remission in about 30% of patients with CD, although escape occurs .Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor–binding profile, with high binding affinity for somatostatin-receptor subtype 5. Pasireotide is the only agent approved by Taiwan FDA for treatement of CD. In a 12-month phase 3 study of Pasireotide in CD, the median urinary free cortisol level decreased by approximately 50% but hyperglycemia-related adverse events developed in 118 of 162 patients. There is still a need for a medical therapy that is more effective and with less adverse effects for patients with CS. A longacting, once-monthly formulation of pasireotide is under clinical development for CD and novel steroidogenesis inhibitors are being developed, such as levoketoconazole and osilodrostat (LCI699).

Retinoic acid decreases ACTH secretion through action on POMC gene transcription, and normalises UFC concentrations in some patients with CD. 59

38

The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE2-1

MICRORNA-MEDIATED NETWORKS UNDERLIE IMMUNE RESPONSE REGULATION IN PAPILLARY THYROID CARCINOMA 1

C-T HUANG, 1Y-J OYANG, 4H-C HUANG, 1,2,3H-F JUAN

1

Graduate Institute of Biomedical Electronics and Bioinformatics, 2 Department of Life Science, 3 Institute of Molecular and Cellular Biology, National Taiwan University, 4 Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific regulation in the direct miRNA2target network among distinctive PTC variants to different extents. Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. Together, our systematic results uncover the intensive regulation of immune responses underlain by miRNA-mediated networks in PTC, opening up new avenues in the management of thyroid cancer.

60

Abstract

SE2-2

LYMPHOCYTIC THYROIDITIS AND PAPILLARY THYROID CARCINOMA ‫ݔ‬ᐚᆌ ‫ݔ‬πߞ۹ख‫܉‬ᚃଲϲϸ‫ུݫ‬ചхᗃऌ

Lymphocytic (Hashimoto’s) thyroiditis is an autoimmune disease in thyroid. The pathogenesis of Hashimoto's thyroiditis is due to a combination of genetic and environmental factors. This disease occurs in 0.3-1.5 per 1000 individuals worldwide and is more predominant in females with gender prevalence ratios of 5 to 20:1.

Papillary thyroid carcinoma is the most common type of thyroid cancer representing > 80% of all thyroid cancer cases. It occurs more frequently in women and presents in the 20-55 years of age. The driver mutations, including BRAF, RAS and PAX8-PPARG, are associated with different histologic variants of papillary thyroid carcinoma and confer distinct patterns of gene expression, signaling and clinical characteristics.

Some reports demonstrate lymphocytic thyroiditis is associated with the development of papillary thyroid carcinoma and is a predictive factor of prognosis. Though this is still a subject of debate. More prospective studies are needed to clarify these correlations.

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The

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE2-3

IMMUNE-RELATED ENDOCRINE ADVERSE EVENTS CHIA-CHI LIN, MD, PHD Department of Oncology, National Taiwan University Hospital; Department of Urology, National Taiwan University College of Medicine

Four monoclonal antibodies targeting immune checkpoint proteins are available for the treatment of patients with melanoma, non-small cell lung, head and neck, kidney, and urothelial cancer as well as Hodgkin lymphoma, and their use will likely expand in the future to additional tumor types.

Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab (anti-CTLA4 antibody), whereas the incidence of thyroid dysfunction is higher with nivolumab / pembrolizumab / atezolizumab (anti-PD1 / PDL1 antibodies). Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of FRUWLFRVWHURLGV RQ WKH HI¿FDF\ DFWLYLW\ RI LPPXQH FKHFNSRLQW LQKLELWLQJ GUXJV LV UHSRUWHG +RUPRQDO GH¿FLHQFLHV DUH RIWHQ SHUPDQHQW In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

62

Abstract

SE3-1

GENETICS OF ENDOCRINE AND METABOLIC DISEASES- OVERVIEW AND COMPLEX DISEASE GENETICS WEI-SHIUNG YANG, MD., PHD. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, and Department of Internal Medicine, NTU Hospital

The genetics of human diseases are generally categorized into monogenic or polygenic (a trendy term is complex disease) in etiology. The monogenic disorders usually reveal a compatible mode of LQKHULWDQFH LQ SHGLJUHH DQDO\VLV &RPPRQO\ D VSHFL¿F IRUP RI PXWDWLRQ LQ D GLVHDVH FDXVLQJ JHQH FDQ be linked to the disease phenotypes. Therefore, looking for a genotype can lead to the diagnosis of a disease. On the other hand, the number of candidate genes for a complex disease can be huge, from ten to hundreds. The predictive value of a genotype is usually very low. However, it is still important not RQO\ IRU ELRORJLFDO SDWKZD\ GLVFRYHU\ EXW DOVR IRU GUXJ WDUJHW ¿QGLQJ $ IHZ H[DPSOHV RI JHQHWLFV LQ diabetes mellitus and autoimmune thyroiditis will be given to illustrate these issues in this talk.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE3-2

MENDELIAN DISEASE IN ENDOCRINE PRACTICE TJIN-SHING JAP, M.D. Division of Endocrinology and Metabolism, Taipei-Veterans General Hospital, School of Medicine, National Yang Ming University, Taipei, Taiwan 112

Single gene inheritance, also referred to as a Mendelian inheritance is a straight forward in pathogenesis and can be utilized in daily endocrine practice because a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene may cause D VLJQL¿FDQW FOLQLFDO FRQVHTXHQFH $ERXW WZR GHFDGHV DJR SULRU WR WKH LQWURGXFWLRQ RI JHQRPH ZLGH association (GWA) studies, the primary investigation method for monogenic disease was through inheritance studies by using positional cloning in the families. The phenotype studies are crucial in a VLQJOH WUDLW GLVHDVH LI WKH GH¿QLWLRQ RI GLVHDVH ZDV FKDUDFWHUL]HG LQ D QDUURZHU ZD\ DQG LW LV PRUH OLNHO\ WKH PXWDWLRQ ZLOO EH LGHQWL¿HG From the experience we earned, early detection of the mutated gene is warranted because surgical intervention may be avoided from one to the other with a proper treatment regimen being administered early in the course of the disease, or even may stop the medication or shift the therapeutic regimen, respectively.

With the recent advance in Genome wide sequencing by using next generation sequencing in hand, scientists right now easily to match monogenic disease phenotypes to their corresponding genes e.g., Allan--Herndon--Dudley syndrome, SHORT syndrome, etc. To keep this in mind, once a diseaseFDXVLQJ PXWDWLRQ LQ WKH '1$ VHTXHQFH RI D JHQH LV LGHQWL¿HG LW LV PXFK HDVLHU WR LGHQWLI\ KRZ WKH corresponding gene product (protein) might work in a manner that alters its biological function. The nature of disease-associated changes in protein structure and function enable the drug hunter in turn to design drugs specifically targeting corresponding proteins in patients with rare disease in which Familial Renal Gucosuria and SGLT2 inhibitor as the example. ,Q FRQFOXVLRQ UH¿QHPHQW LQ VHTXHQFLQJ WHFKQLTXHV DQG ELRLQIRUPDWLFV ZLOO LQFUHDVH WKH GHWHFWLQJ rate of mutations. Early diagnosis of monogenic endocrine disease is necessary, not luxury one. The patients with rare disease may provide a clue for drug discovery. Genetic counseling is a part of practice

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Abstract

SE3-3

Precision Medicine and Clinical Genetic Testing 1,2,3,4

PEI-LUNG CHEN, MD, PHD

1

Department of Internal Medicine, 2Department of Medical Genetics, National Taiwan University Hospital; Graduate Institute of Medical Genomics and Proteomics, 4Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan

3

Precision medicine, according to the National Institutes of Health (NIH), USA, is “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person”. Under this approach, diagnostic testing is often employed for diagnosis and/or for selecting appropriate therapies based on the patient’s genetic content. Given that the genetic models of diseases (for example, single gene disease vs. complex disease) can vary from diseases to diseases, the most appropriate method for genetic testing therefore will also keep evolving. In addition to traditional platforms (such as Sanger sequencing, multiplex ligationGHSHQGHQW SUREH DPSOL¿FDWLRQ 0/$ DUUD\ &*+ HWF QH[W JHQHUDWLRQ VHTXHQFLQJ 1*6 KDV EHHQ UHYROXWLRQL]LQJ WKH ¿HOG RI JHQHWLF WHVWLQJ GXULQJ WKH ODWHVW \HDUV ,Q WKLV SUHVHQWDWLRQ WKH SULQFLSOHV RI precision medicine and the state-of-the-art methodologies of clinical genetic testing will be illustrated.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE4-1

CHROMOGRANIN A AND NEUROENDOCRINE TUMORS ‫ڻ‬Н‫ڐ‬ ‫ݔ‬πߞ۹ख‫܉‬ᚃଲလድऌ

Gastroenteropancreatic neuroendocrine tumor (GEP NET) is the second prevalent malignancy in gastrointestinal tract. The prevalence rate was twice higher than pancreatic cancer in United State.

The incidence and prevalence of NETs increased approximately 500% over the past 30 year, which may be partially due to improvement of diagnosis and clinical awareness. The diagnosis of GEP NET is difficult because of confusion nomenclature and the varieties of cell differentiated in pathologic specimen, from poorly differentiated carcinoma to well-differentiated tumors. GEP NET also exhibits a wide spectrum of clinical behavior. The initial clinical symptoms are often indolent and some of WXPRUV VHFUHWHG IXQFWLRQDO SHSWLGHV VXFK DV FDUFLQRLG V\QGURPH ZLWK ÀXVKLQJ DQG GLDUUKHD An accurate diagnosis in GEP NET is important because their diverse tumor behavior, drug of choice for systemic therapy and the predicted tumor response under systemic therapy, which are very different to exocrine carcinoma in gastrointestinal tract. Additionally, classic biomarkers such as CEA and CA199, which were widely used in exocrine carcinoma in evaluate disease status and monitor response to systemic therapy, were useless in GEP NET. Chromogranin A (CgA) is a 439 amino acid protein and belongs to one of granin family, which is a principle component of dense-core granule in neuroendocrine cells (7). CgA expression generally correlates with dense-core granule numbers within neuroendocrine cells. Neuroendocrine cells cosecrete CgA and hormone during the secretory granule exocytotic process, thus CgA had been reported as a marker of neuroendocrine cell activity (9). Serum CgA had been used as a biomarker in diagnosis, evaluation of tumor status and evaluate tumor response under systemic therapy in GEP NET. However, the experiences and clinical values of CgA in GEP NET were limited out of western countries. The purpose of this section was to evaluate the clinical roule of serum CgA levels with disease status and treatment response in GEP NET patients in Taiwan.

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Abstract

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MEDICAL TREATMENT FOR NEUROENDOCRINE TUMORS (NET): FOCUSING ON PANCREATIC/MIDGUT NET AND TARGETED THERAPY CHIUN HSU Graduate Institute of Oncology, National Taiwan University College of Medicine; Department of Oncology, National Taiwan University Hospital; National Taiwan University Cancer Center, Taipei, Taiwan

Pancreatic NET and other midgut-derived NET are used to be considered as distinct disease entities because of their different clinical presentation and responses to systemic therapy. Results from molecular genetics also implied that they have distinct pathogenic processes. Molecular targeted agents, including the mTOR inhibitor everolimus and the multikinase inhibitor sunitinib, are approved for the treatment of low-grade, advanced pancreatic NET, whereas somatostatin analogues are used for other midgut NETs. In this presentation updated results from clinical trials of molecular targeted agents, along or in combination, and radiolabeled somatostatin analogue therapy will be summarized and the evolving landscape of clinical trials will be discussed.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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FUTURE OUTLOOK OF GEP-NETS IN TAIWAN AND TREATMENT PARADIGMS UPDATE YAN-SHEN SHAN MD, PHD Distinguished Professor and Director; Department of Clinical Medicine Research; Division of General Surgery, Department of Surgery, NCKUH; Institute of Clinical Medicine, College of Medicine, NCKU, Tainan, Taiwan ROC

Since introduction of new classification of GEP-NET on 2010, there is a great change in the DWWLWXGH RI PDQDJHPHQW IRU *(3 1(7 6XFFHVVIXO ELRORJLFDO WKHUDS\ DQG WDUJHW WKHUDS\ VLJQL¿FDQWO\ improve patient survival and quality of life. Aggressive surgical resection for primary NETs and metastatic NETs were done based on the advanced image studies and improvement of surgical technique and postoperative care. TCOG has launched a registry trial for recording of NETs since 2013. After management of this rare tumor, we found several emergent needs in management of GEPNET should be discussed in future. 1. The role and regimen as neoadjuvant therapy for metastatic *(7 1(7V +RZ WR WUHDW KLJK * SDWLHQWV DIWHU UHVHFWLRQ E\ DGMXYDQW VHWWLQJ" 7KH XVDJH RI biological therapy/ target therapy after resection in metastatic GEP-NETs 4. The exact role CgA in the following of GEP-NETs. Here, we will present our experience in the management of GEP-NETs based on these points.

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Abstract

SE4-4

NEUROENDOCRINE TUMOR AND MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 S-R S National Taiwan University College of Medicine, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with an estimated incidence of 0.25%. It is characterized by the occurrence of parathyroid adenomas, gastropancreatic neuroendocrine tumors (NET) and anterior pituitary tumors. Diagnosis of MEN1 is established in an individual by one of three criteria: the occurrence of two or more MEN1-associated endocrine tumors; WKH RFFXUUHQFH RI RQH RI WKH 0(1 DVVRFLDWHG WXPRUV LQ D ¿UVW GHJUHH UHODWLYH RI D SDWLHQW ZLWK 0(1 DQG LGHQWL¿FDWLRQ RI D JHUPOLQH MEN1 mutation. Respective tumors occurring in MEN1 patients tend to be larger, more aggressive and resistant to treatment than those occurring in non-MEN1 patients.

Individuals having a high risk of developing MEN1-associated tumors should be offered a program of combined clinical, biochemical and radiological screening. According to the guidelines, screening of gastropancreatic NET should include an annual plasma biochemical evaluation of a IDVWLQJ JDVWURLQWHVWLQDO WUDFW KRUPRQH SUR¿OH LQFOXGLQJ JDVWULQ JOXFDJRQ YDVRLQWHVWLQDO SRO\SHSWLGH (VIP), pancreatic polypeptide, chromogranin A, and insulin. Annual pancreatic and duodenal visualization with magnetic resonance imaging, computed tomography, or endoscopic ultrasound was also suggested. However, the nature and timing of screening will depend on local resources, clinical judgement and patient preferences. Patients with MEN1 should be managed by a multidisciplinary team. The main aim of treatment is to maintain disease- and symptom-free and to maintain a good quality of life.

On the other hand, the association of MEN1 is 25-40% in gastrinoma, 5% in insulinoma, 20% in non-syndromic NET, 45% in somatostatinoma, 10% in gastrinoma, and 5% in VIPoma. Clinical examination and family history survey to exclude complex cancer syndromes including MEN1 were suggested to be performed in all cases of NETs in guidelines. Screening strategy including appropriate biochemical and radiological investigations also depends on local resource and clinical judgement.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE5-1

DEBATE AND CONSENSUS OF THYROID TUMOR MANAGEMENT IN TAIWAN S-T CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Up to 30% of well-differentiated thyroid cancer (WDTC) patients may experience a clinically significant recurrence throughout their lifetime. Since that the currently used AJCC/UICC staging V\VWHP LV GHVLJQHG WR SUHGLFW GLVHDVH VSHFL¿F PRUWDOLW\ LW LV OLPLWHG WR DFFRXQW IRU ORQJ WHUP UHFXUUHQFH and/or disease persistence. The truth of the ongoing and dynamic risk of WDTC recurrence led to the FRQFHSW RI ULVN VWUDWL¿FDWLRQ WR WDLORU D WUHDWPHQW DQG PRQLWRULQJ SODQ WR PLQLPL]H ULVN DQG PD[LPL]H EHQH¿W $FFRUGLQJ WR WKH ORQJ WHUP IROORZ XS VWDWXV RI WKH GLVHDVH PXOWLWXGH RI YDULDEOHV QRW LQFOXGHG in AJCC/UICC staging were incorporated in 2009 by the American Thyroid Association (ATA). The UHYLVHG JXLGHOLQHV IRU WUHDWPHQW RI WK\URLG FDQFHU WKXV SURSRVHG D ULVN VWUDWL¿FDWLRQ V\VWHP WR SUHGLFW risk of disease recurrence to classify patients as low, intermediate, or high risk for recurrence. After a follow-up for a median of 7 years after their original treatment, Tuttle et al. added in a response-toWKHUDS\ YDULDEOH LQWR WKH $7$ ULVN VWUDWL¿FDWLRQ V\VWHPV WR IXUWKHU LGHQWLI\ SDWLHQWV ZKRVH GLVHDVH LV likely to recur versus those likely to remain disease-free. Accordingly, management algorithms for low, intermediate and high risk WDTC were illustrated in the 2015 ATA guideline; even so, topics such as management of micropapillary thyroid cancer, the need of postoperative radioactive iodine ablation, the need of central neck dissection, etc. still remains room for debate.

Additional tools such as biochemical markers (for example, the expression of NIS, VEGF receptors, etc), genetic mutations (RAS, RET/PTC, BRAF) and molecular markers for distant PHWDVWDVLV KDYH EHHQ DWWHPSWHG WR DGG WR WKLV FRPSOH[ ULVN VWUDWL¿FDWLRQ SURFHVV ZLWK DV \HW XQFHUWDLQ validity.

70

Abstract

SE5-2

NUCLEAR MEDICINE-RELATED DEBATES AND CONSENSUSES OF DIFFERENTIATED THYROID CANCER MANAGEMENT IN TAIWAN 1,2, 3

DHY SHEN

1

Department of Nuclear Medicine and PET Center, 2Integrated thyroid cancer management group, TSGH TriService General Hospital (TSGH), National Defense Medical Center (NDMC), Taipei, Taiwan; 3Society of Nuclear Medicine, Taiwan, R.O.C.

Follicular-epithelial origin thyroid cancers including papillary and follicular cancers constitutes about ~90% of thyroid malignancies and are collectively named as differentiated thyroid cancers (DTCs). The majority of DTCs are avid for radioactive iodine (RAI) and thus allow RAI to be used as therapeutic or diagnostic modality. I-131 treatment is mainly (1) to eradicate post-thyroidectomy remnants, (2) to abolish microscopic lesions if any and (3) to control macroscopic tumors as possible.

RAI, such as I-123, I-124 and I-131 can provide functional imaging to delineate the whole body tumor involvement and differentiation status (i.e. functioning Na+/I- symporter expression). Recently the DTC management paradigm has been evolving to be more conservative regarding RAI use: recommendation of routine I-131 treatment has been weakened and pre-therapy diagnostic RAI scan LV QRW DOZD\V VXJJHVWHG 6R FDOOHG $PHULFDQ 7K\URLG $VVRFLDWLRQ $7$ ULVN FODVVL¿FDWLRQ V\VWHP KDV been proposed to justify or defy RAI use while such implementation needs to be agreed by different specialties involved in thyroid tumor management. Furthermore, ever-lasting controversy regarding with the adequate dose or activity of RAI use for DTCs has not been well solved. Either dosimetrybased or empiric practice is still of controversial. Also the treatment interval of repeated RAI treatment and maximally cumulative dose limit has not been well addressed. In very recent days, the term of RAI-refractory DTC has emerged and calls for more attention to realize the appropriate use of RAI treatment.

Conventionally RAI whole body scans (WBS) in conjunction to serum thyroglobulin (Tg) checkup are used for tumor surveillance and, in certain situation, cross-section imaging (i.e. CT and MRI) and PET/CT might be needed. The intensity of RAI WBS follow up has also been challenged by ATA ULVN FODVVL¿FDWLRQ V\VWHP $OWHUQDWLYHO\ WKH XVH RI ) ÀXRURGHR[\JOXFRVH )'* 3(7 &7 KDV EHHQ proven useful to detect de-differentiation of DTCs. Thus its indication might need to extend to (1) advanced staged tumor (e.g. pT4 or M1 disease) or (2) unproportionally elevated serum Tg level in DTCs.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE5-3

MANAGEMENT OF WELL DIFFERENTIATED THYROID CANCER TAILORED THROUGH RISK STRATIFICATION HURNG-SHENG WU Asia Institute Tele-Surgery; Chang-Bing Show-Chwan Memorial Hospital National Defense Medical Center and Tri-Service General Hospital Taiwan Association of Endocrine Surgeons

Thyroid cancer is the most common malignancy of endocrine disease, the incidence of thyroid cancer and the number of patients are increasing globally. Well-differentiated thyroid cancer(WDTC) of follicular cell origin represent more than 90% of thyroid malignancies, which involve two major histological types, papillary thyroid cancer(PTC) and follicular thyroid cancer(FTC). For patients with WDTC have an excellent prognosis, some patients die from progressive tumor.

Well established prognostic factors including metastases, age, tumor size, extrathyroid extension, complete of resection and gender. According to these risk factors, the extent of surgical resection of the thyroid and neck lymph node dissection is decided preoperatively. After surgery thyroid remnant ablation with 131I and TSH suppression with L-thyroxine were the triad of initial therapy recommended for most patients. However, recently several approaches were reported that risk recurrence and death from thyroid cancer in individual patients with various clinical parameters that become available postoperatively. These factors include histological subtype, 131I whole body scintigraphy findings, response to 131I treatment. Serum thyroglobulin(Tg) levels under TSH stimulated or not stimulated conditions and change in serum Tg antibody(TgAb) concentration after surgery. WDTC with no detectable TgAb, Tg-doubling time seems to be the most powerful predictor of prognosis, whereas, WDTC with TgAb, change in serum TgAb concentration seems to be the best predictor of outcome.

Three-level stratification to assess risk of recurrence after surgery. Low-risk patients: no local or distant metastases; all macroscopic tumor has been resected; there is no tumor invasion of locoregional tissue or structures, the tumor did not have aggressive histology or vascular invasion and no 131 I uptake outside the thyroid.

Intermediate-risk patients have any of the following: microscopic invasion of tumor into the perithyroidal soft tissue; cervical lymph node metastases or 131I uptake outside the thyroid bed or tumor with aggressive histology or vascular invasion. High-risk patients have macroscopic tumor invasion, incomplete tumor resection, distant metastases, and 131I high serum Tg level to what is seen on posttreatment scan.

Molecular testing in BRAF mutation as a risk factor that is an important tool guidance toward the personalization surgery in PTC. Depend on the risk assessment in individual patients with these approached, concerning risks of recurrence and death from WDTC are better predicted, large dose 131I may be avoided in low risk patients and more appropriate intensity and methods for follow-up studies.

72

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WS1-1

ISLET BIOLOGY AND TRANSPLANTATION J-H JUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Taiwan

The pancreatic islets of Langerhans have been intensively investigated, largely because of their central role in the pathogenesis of type 1 and type 2 diabetes mellitus. Research studies centered on WKH ELRORJ\ UHJHQHUDWLRQ DQG WUDQVSODQWDWLRQ RI LVOHWV FRQWLQXH WR VKHG VLJQL¿FDQW XQGHUVWDQGLQJ RQ the development of different forms of diabetes and provide further impetus for the quest to find a “cure.” Restoring E-cell mass and reversing diabetes can be accomplished by two approaches: either by endogenous regeneration of E cells or transplantation of E cells from exogenous sources; recent advancements in science and technology have facilitated progress in both. The following are examples RI RXU UHVHDUFK ZRUN LQ WKLV ¿HOG It has been shown all-trans retinoid acid (ATRA) hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 stimulates growth and differentiation of E cells as well as exerts antiapoptotic effect on E cells. Thus, we tested if the combination therapy with ATRA and exendin-4 could prevent and rescue diabetes in NOD mice with and without islet transplantation. We found ATRA and ATRA plus exendin-4 treatment delayed the onset of diabetes.

However, after the onset of autoimmune diabetes, ATRA and/or exendin-4 treatment is unable to reverse hyperglycemia or improve survival in NOD mice with and without islet transplantation.

To better understand the fate of islet isografts and allografts, we utilized a magnetic resonance (MR) imaging technique to monitor mouse islets labeled with a novel MR contrast agent, chitosancoated superparamagnetic iron oxide (CSPIO) nanoparticles. After incubation of mouse islets with CSPIO, TEM showed CSPIO in endocytotic vesicles of D and E cells at 8 h. Incubation with CSPIO did not affect insulin secretion and death rates of islets. After syngeneic and allogeneic transplantation, grafts of CSPIO-labeled islets were visualized on MR scans as persistent hypointense areas. At 8 weeks after syngeneic transplantation and 31 days after allogeneic transplantation, histology of CSPIO-labeled islet grafts showed colocalized insulin and iron staining in the same areas but the size of allografts decreased with time. TEM with elementary iron mapping demonstrated CSPIO distributed in the cytoplasm of islet cells, which maintained intact ultrastructure.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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THROID CANCER CELL BIOLOGY S-T CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

The normal thyrocytes are highly differentiated TSH-dependent iodine concentrating hormone secreting cells. Cancers develop in thyroid because of intrinsic and/or extrinsic factors that lead to genetic mutations, DNA methylations, aberrant RNA/protein and miRNA expression. The frequently found molecular markers such as RAS, BRAF, RET/PTC and PTEN mutations lead to oncogenic activation and/or suppressor gene inactivation through integrating PI3K and MPAK pathways and eventually ensure tumorigenesis. Cancer cells gain eternity and metastasis abilities in expense of losing differentiation, that is, the ability to produce thyroglobulin and concentrate iodine. Although the mechanism of dedifferentiation is not fully understood, certain histone deacetylase inhibitors do restore the expression of NIS gene in vitro as well as in vivo.

7R ¿W WKH OLPLWOHVV JURZWK WKH PHWDEROLVP RI FDQFHU FHOOV GLIIHUV E\ LQFUHDVLQJ JOXFRVH XSWDNH and enhancing aerobic glycolysis through the activation of transcription factors and coactivators such as HIF1a and PGC1a under AMPK regulation. In correspondence, treatment with metformin, an AMPK activator, was found to associate with decreased thyroid cancer risk and improved patient survival.

Cancer metastases involves complex local as well as systemic factors, which include the ability of cancer cells to invade the surrounding normal host tissues including small lymphatic or vascular channels, survival from the host immune surveillance, and finally, colonization and growth of the disseminated tumor cells. The preference of hematogenous and lymphatic spread of follicular and SDSLOODU\ W\SHV RI WK\URLG FDQFHU LPSOLHV GLIIHUHQW PRGH RI PHWDVWDVLV UHTXLULQJ VSHFL¿F VWUDWHJ\ IRU treatment.

74

Abstract

WS1-3

GENETIC STUDIES IN OBESITY AND DIABETES ஼п‫ܜ‬ ᇄτᚃᏱଲஆӱᡞᄳ೗ҪᡞᚃᏱः‫ܛف‬

Recent progress in genetic studies, especially with the advent of genomewide association studies (GWAS) and next-generation sequencing greatly forward our understanding towards these two complex human traits.

For obesity, currently ~97 common variants are associated with BMI variations, which account > 20% of BMI variation. Pathway analysis provides strong support for the genes involved in central nervous system process, insulin secretion and action, energy metabolism, lipid biology/adipogenesis, RNA binding protein, MAP kinase singling, and cell proliferation/survival. The PRVW LQÀXHQWLDO LQWURQLF YDULDQW LQ WKH FTO gene is now believed to harbor an enhancer of a downstream gene involved in browning of fat cells.

For, type 2 diabetes mellitus and related glycemic traits, including fasting glucose and insulin resistance index identified ~ 100 common variants association with glycemic traits. Most genes are involved in insulin secretion and beta cell survival/proliferation. Other genes included nocturnal rhythm, adrenergic signaling, and lipid synthesis.

Although traits identified form large-scale genome-wide association study only can explained < 20 % of heritability of BMI or type 2 diabetes. Recent whole-genome sequencing did not identify rare variants associated with obesity and diabetes that can explain the “missing heritability”. In addition, most of WKHVH UDUH YDULDQWV DUH IRXQG LQ WKH SUR[LPLW\ RI ORFL SUHYLRXVO\ LGHQWL¿HG IURP GWAS or monogenic diabetes/obesity.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

WS2-1

DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS: AN UPDATE ؄࡛ࠓᚃ৲ ᇄτᚃଲ

Gestational diabetes mellitus (GDM) is defined when diabetes is diagnosed during pregnancy for the first time. Women with GDM have increased risk for adverse perinatal outcomes, including macrosomia, birth trauma, jaundice, respiratory distress syndrome, primary cesarean section, and maternal hypertensive disorders. After delivery, 15-50% of women with GDM develop type 2 diabetes later in life. Besides, children and adolescents with higher birth weight are associated increased risk of obesity and diabetes as well.

The diagnosis of GDM is firstly proposed by O’Sullivan, using 100g, 3-hour oral glucose tolerance tests (OGTT) to predict maternal diabetes after delivery. In 1982, Carpenter and Coustan (C&C) revised the cutoffs again, since the risk of adverse fetal outcomes increases above these cutoffs.

In clinical practice, the 100g OGTT is usually preceded by a 50g glucose challenge test (GCT) as a screening test. In 2008, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study used 75g, 2-hour OGTT to define cutoffs which predict adverse fetal and maternal outcomes. Based on the findings, the International Association of the Diabetes and Pregnancy Study Group (IADPSG) proposed a new diagnostic strategy using 75g OGTT, which was adopted by the ADA in 2011. In our hospital, we adopted the IADPSG criteria since 2011 until now. Our college compares the perinatal outcome between two groups using the C&C criteria and the IADPSG criteria. The result show that adopting the IADPSG criteria improves perinatal outcomes and is cost-efficient, at the expense of increased prevalence of GDM.

76

Abstract

WS2-2

SCREENING OF GESTATIONAL DIABETES MELLITUS: EXPERIENCE IN TAIWAN ഍߹՝ ུіҀҴᖓӬᚃଲϲऌഌུചхᗃऌ

Pregnant women with gestational diabetes mellitus (GDM) have higher risk for adverse perinatal outcomes, including macrosomia, birth trauma, neonatal jaundice, infant respiratory distress syndrome, hypertensive disorders of pregnancy, and the need for primary cesarean section. In addition, 15-50% of these GDM women develop type 2 diabetes later in life. Furthermore, based on reports from our group and others, children and adolescents with higher birth weight are associated with increased risk of obesity and diabetes. Therefore, we sometimes call GDM “a disease across two generations”.

It is thus imperative to screen and diagnose GDM since timely intervention can alter the development of short and long-term complications in both the mother and child. However, it is currently lack of consensus on a method for screening given the uncertainty of which subjects can truly EHQH¿W IURP LW DQG WKH YDULRXV GLDJQRVWLF FULWHULD RI *'0 %DVLFDOO\ WKHUH DUH WZR NLQGV RI VFUHHQLQJ methods, one is selective and the other is universal. The selective screening is risk-based, using traditional risk factors (e.g., previous history of GDM, a family history of diabetes) to select women at risk, who will proceed with biochemical screening. However, one-third to near half of women with GDM by this method would be missed. In this way, most guidelines prior to 1995 recommended universal biochemical screening.

The most adopted biochemical exam is an oral glucose tolerance test (OGTT), including two-step approach with a glucose tolerance test plus a 3-hour OGTT and one-step 2-hour OGTT. This is actually time-consuming for mothers and labor-intensive for the laboratory. Some women may feel nauseated, sweaty, or lightheaded after drinking the glucose solution, which results in moderately high “no-show” rate in the two-step screening. Several alternative screening methods have been advocated to decrease the need of OGTT, i.e., methods that combine risk factors, glucose challenge tests, fasting glucose levels or risk prediction algorithms. In this presentation, I will introduce one of alternative screening PHWKRGV LQ 7DLZDQ ZKLFK FDQ UHGXFH WKH QHHG RI 2*77 ZLWK IDLU VHQVLWLYLW\ DQG VSHFL¿FLW\

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

WS2-3

TREATMENT OF GESTATIONAL DIABETES MELLITUS H-Y LI National Taiwan University Hospital, Taipei, Taiwan

Gestational diabetes mellitus (GDM) results in increased risk of various pregnancy complications, ZKHUHDV WUHDWPHQW IRU *'0 FDQ UHGXFH WKHVH FRPSOLFDWLRQV VLJQL¿FDQWO\ /LIHVW\OH PRGL¿FDWLRQ DQG VHOI PRQLWRU RI EORRG JOXFRVH E\ JOXFRPHWHU DUH WKH ¿UVW VWHS IRU JO\FHPLF FRQWURO 7KH WUHDWPHQW JRDO for GDM in Taiwan follows the recommendation from the 5th International Workshop-conference on GDM, including fasting plasma glucose 95 mg/dl, 1-hour postmeal plasma glucose 140 mg/dl, and 2-hour postmeal plasma glucose 120 mg/dl. If glycemic control fails to achieve these goals by OLIHVW\OH PRGL¿FDWLRQ LQ ZHHNV PHGLFDWLRQV VKRXOG EH FRQVLGHUHG ,QVXOLQ DQG LQVXOLQ DQDORJXHV including regular insulin, NPH, insulin aspart, insulin lispro and insulin detemir, can be used to control GDM. The initial dose and titration methods will be discussed in the talk. Metformin and glyburide can be considered to treat GDM. Metformin has been shown to have better glycemic and weight control than insulin, and it may be a better choice than glyburide. Glyburide has been shown to be able to achieve similar glycemic control, compared with insulin. However, glyburide is associated with an increased birth weight and a higher risk of neonatal hypoglycemia. The long-term effect for the use of glyburide and metformin remains unknown. Six to twelve weeks after delivery, an oral glucose tolerance test should be arranged to diagnose if the woman has diabetes or not.

78

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ME

ADRENAL AND PITUITARY CLINICAL PEARLS WILLIAM F. YOUNG, JR., MD, MSC Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

The goal of this interactive session is to provide a fast-paced and clinically engaging session where “bite-sized” pieces of clinically relevant information are shared. Clinical scenarios will be presented that illustrate clinically important endocrine teaching points, “Endocrine Pearls”, which are relevant to the practicing endocrinologist but not widely appreciated. I will present approximately 8 cases in the following format: x Case presentation x Multiple choice question based on the case x Use audience response system to weigh in on the best answer x Review the answers x Review the correct answer and provide the pearl(s) x Move on to the next case x After the last case we will have time for questions and answers x An electronic PDF of the correct answers and pearls learned will be provided at the conclusion of the session.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

MD-1

PATHOGENESIS OF OSTEOPOROSIS AND OSTEOPOROTIC FRACTURES IN PATIENTS WITH DIABETES J-F KUO Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan, ROC

Both type 1 (T1DM) and 2 diabetes (T2DM) are associated with an increased risk of fracture.

Although bone mineral density (BMD) is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. On the other hand, bone loss as determined by Dual-energy X-ray absorptiometry (DXA) occurs more rapidly in type 2 diabetic postmenopausal women. Fracture risk in T2DM is higher for a given BMD T-score and age or for a given Fracture Risk Assessment Tool (FRAX) score. Bone strength consists of BMD and bone quality, which suggests that factors other than BMD play a major role in bone quality in diabetes.

The skeletal system seems to be an additional target of diabetes-mediated damage, leading to the development of diabetes- induced osteoporosis. Mechanisms of diabetes- induced bone fragility including low bone turnover, accumulation of advanced glycation end products (non-enzymatic glycosylation of collagen) with micro and macro-architecture alterations (increased cortical porosity) that cause reduced resistance to mechanical stress, pro-inflammatory state with increased oxidative VWUHVV DGLSRNLQHV G\VUHJXODWLRQ LQVXOLQ GH¿FLHQF\ RU DOWHUHG LQVXOLQ VLJQDOLQJ ORZ OHYHO RI LQVXOLQ like growth factor 1, loss of incretin effect, increased marrow fat. Complications of DM increase the risk of falls and fracture including peripheral neuropathy, orthostatic hypotension, sarcopenia, YLVLRQ LPSDLUPHQW DQG IUHTXHQW K\SRJO\FDHPLF HYHQWV 9LWDPLQ ' GH¿FLHQF\ K\SRJRQDGLVP XVH RI DQWLGLDEHWLF PHGLFDWLRQV WKLD]ROLGLQHGLRQHV FDQDJOLÀR]LQ PLJKW DOVR FRQWULEXWH WR LQFUHDVHG IUDFWXUH risk.

80

Abstract

MD-2

PHARMACOLOGIC TREATMENT FOR OSTEOPOROTIC FRACTURES IN PATIENTS WITH DIABETES JAWL-SHAN HWANG, MD Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

Osteoporosis and diabetes are two common diseases in developed countries that are related to the aging of population, as well as in Taiwan. Osteoporosis characterized by a decrease in bone mass and deterioration in skeletal microarchitecture, which lead to increased fragility and susceptibility to fractures.

There is clear evidence that type 1 and type 2 diabetic patients have a higher fracture risk than nondiabetic people. However, the risk of osteporotic fractures in these patients does not correspond to low bone mineral density as measured by dual energy X-ray absorptiometry. Actually, the majority of the studies carried out in T2DM patients have shown a BMD normal or paradoxically higher than nondiabetic controls, where fracture risk is increased in patients despite normal or even high bone PLQHUDO GHQVLW\ 7KLV LPSOLHV WKDW GH¿FLHQFLHV LQ WKH ERQH WLVVXH LWVHOI UDWKHU WKDQ WKH DPRXQW RI ERQH present, are the cause of reduced bone strength. The parameters that describe the mechanical behavior RI ERQH FDQ EH GLYLGHG LQWR WZR FDWHJRULHV ([WULQVLF SURSHUWLHV GH¿QH WKH ZKROH ERQH PHFKDQLFV H J failure load and energy absorption), while intrinsic properties describe the mechanics of the bone tissue (e.g. failure stress and toughness). Bone mass, structure and intrinsic material properties all contribute to the extrinsic or whole-bone mechanics. Causes of reduced bone tissue mechanics in diabetes may include reduced bone turnover, increased porosity and the accumulation of non-enzymatic collagen cross-links known as advanced glycation end-products. These cross-links form spontaneously through non-enzymatic glycation, and are known to affect bone mechanics directly by reducing extrinsic and intrinsic properties, and indirectly by inhibiting osteoblast function, in particular in combination with high levels of glucose.

In clinical practice, the diagnosis of osteoporosis in diabetic patient needs further investigations beyond the measurement of BMD. Bone health should be considered part of the diabetic management algorithm, and monitored as diligently as are diabetic eye examinations, cholesterol levels or foot care. Currently, not all guidelines include bone health as a part of diabetes care. The general recommendations for the intake of calcium, vitamin D should be applied to the diabetic population.

Exercise should be greatly encouraged in patients with diabetes. The focus should be in understanding the pathophysiology of bone fragility in diabetics, so that appropriate therapies directed at the underlying cause of decreased BMD can be used. Further studies need to be conducted to guide clinicians toward appropriate screening and the best possible treatment modalities available for bone fragility in diabetics.

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AP-1

THE LINK BETWEEN NON-ALCOHOLIC FATTY LIVER DISEASE AND INSULIN RESISTANCE BY HEPATOCYTE-DERIVED FIBRINOGENRELATED PROTEIN 1 1,2

H-T WU, 3 H-Y OU, 3H-C HUNG, 2F-H LU, 2J-S WU, 2Y-C YANG, 2C-J CHANG

1

Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan, R.O.C. 2Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan, R.O.C. 3Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan, R.O.C.

OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is highly correlated with insulin resistance (IR); however, the link between these two diseases was still obscure. It was known that KHSDWRF\WH GHULYHG ¿EULQRJHQ UHODWHG SURWHLQ +)5(3 LV D KHSDWRNLQH WKDW SOD\V DQ LPSRUWDQW UROH in hepatogenesis in embryonic stage, whereas the role of this protein in NAFLD and IR was unknown.

Thus, the aim of this study was to clarify the role of HFREP-1in these two diseases.

MATERIAL AND METHODS A total of 200 healthy and diabetic patients with or without NAFLD was enrolled for the determination of plasma HFREP-1 concentrations by commercial assay kits. Lentiviral vectors containing HFREP-1 or short hairpin RNA targeted to HFREP-1 were injected through portal vein in mice to overexpress or knockdown HFREP-1. Glucose and insulin tolerance tests, as well as hyperinsulinemic-euglycemic clamp were used to evaluate insulin sensitivity. HepG2 hepatocellular carcinoma cell line was used for the investigation of mechanisms in detail.

RESULT In this study, we found that plasma HFREP-1 concentrations were significantly increased in subjects with prediabetes, including impaired fasting glucose and impaired glucose tolerance, and gradually increased in diabetic patients. In addition, plasma HFREP-1 concentrations ZHUH VLJQL¿FDQWO\ LQFUHDVHG LQ VXEMHFWV ZLWK 1$)/' WKDQ WKRVH ZLWKRXW LW +HSDWLF RYHUH[SUHVVLRQ RI HFREP-1 induced lipid accumulation in liver and systemic IR through an ERK1/2-dependent pathway.

On the other hand, knockdown of hepatic HFREP-1 improved high fat diet-induced NAFLD and IR. CONCLUSION HFREP-1 is a novel therapeutic candidate to combat NAFLD and IR.

82

Abstract

AP-2

LIRAGLUTIDE PREVENTS AND REVERSES MONOCROTALINEINDUCED PULMONARY ARTERIAL HYPERTENSION BY SUPPRESSING ET-1 AND ENHANCING ENOS/SGC/PKG PATHWAYS M-Y LEE1,2,3, K-B TSAI4, J-H HSU5,6, S-J SHIN2, J-R WU5,6, J-L YEH1,7 1

Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 3Department of Internal Medicine, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung, Taiwan. 4Department of Pathology, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung, Taiwan.

5 Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 6Department of Pediatrics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 7Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan.

2

OBJECTIVE Liraglutide, a glucagon-like peptide-1 receptor agonist, is widely used to treat diabetes. However, its effect on pulmonary arterial hypertension is unknown. In this study, we investigated its effects on rats with monocrotaline-induced PAH and mechanisms on rat pulmonary artery smooth muscle cells.

METHOD Liraglutide was investigated for both prevention and treatment of MCTinduced PAH. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immunereactivity of endothelial nitric oxide synthase, endothelin-1 and cyclic guanosine monophosphate levels, protein expressions of eNOS, soluble guanylyl cyclase, protein kinase G and Rho kinase II pathway were measured in both in vivo and in vitro. Cell migration and cell cycle were also determined.

RESULT Liraglutide both prevented and reversed MCT-induced PAH, right ventricle hypertrophy and pulmonary vascular wall remodeling. Protein expression of ROCK II was increased while eNOS, sGC and PKG were decreased. Pretreatment with liraglutide inhibited platelet-derived growth factorBB stimulated PASMCs migration, which were associated with cell-cycle arrest at G0/G1 phase.

CONCLUSION Liraglutide may have both preventive and therapeutic effects on MCTinduced PAH, through the eNOS/sGC/PKG and Rho kinase pathways. Thus, liraglutide may have a therapeutic role in pulmonary vascular remodelling.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-3

IRAK1, A TARGET OF MIR-146B, REDUCES CELL AGGRESSIVENESS OF HUMAN PAPILLARY THYROID CARCINOMA 1,2

CHEN-KAI CHOU, 3SHUN-YU CHI , 1CAI-HUA HUANG, 3FONG-FU CHOU, 4CHAOCHENG HUANG, 1RUE-TSUAN LIU,, 2HONG-YO KANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, 2 Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan, Departments of 3Surgery, 4Pathology Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan,

Objective: MicroRNA (miR)-146b is overexpressed in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal invasion, advanced tumor stage, and poor prognosis. However, the underlying mechanism of miR-146b in relation to its oncogenic behavior in PTC and its putative targets remain unknown. The purpose of this study was to investigate interleukin-1 receptor-associated kinase 1 (IRAK1) as the potential miR-146b target gene and its involvement in PTC. Design: :H XVHG JHQRPH ZLGH PLFURDUUD\ FRPSXWDWLRQDO DQDO\VLV DQG ƍ 875 UHSRUWHU JHQH assays to identify IRAK1 as a miR-146b target gene. In vitro gain/loss-of-function experiments were further performed to determine the effects of IRAK1 on proliferation, colony formation, and woundhealing in PTC cancer cell lines. Expression levels of miR-146b and IRAK1 of 50 cases of PTC and its adjacent normal thyroid specimens were assessed via quantitative real-time polymerase chain reaction.

Results: Microarray expression profile revealed that the mRNA level of IRAK1 gene was downregulated by miR-146b. 7KH ƍ 875 RI IRAK1 mRNA was found to be a molecular target of miR146b posttranscriptional repression in BCPAP cells by reporter gene assays. MiR-146b promoted the migration and proliferation of PTC cells by downregulating IRAK1 expression, whereas restoration of IRAK1 expression reversed this effect. In addition, the expression of IRAK1 mRNA ZDV VLJQL¿FDQWO\ lower in PTC clinical tissue samples than normal adjacent thyroid specimens and showed a strong inverse correlation with the expression of miR-146b in PTC specimens.

Conclusion: Our results demonstrated that IRAK1 is a direct target of miR-146b and has functional roles to inhibit various aggressive PTC cell activities. In conjunction with current therapeutic regimens, targeting the miR-146b-IRAK1 axis may provide a potential approach for PTC management.

84

Abstract

AP-4

CARDIOTROPHIN-1 IS INVERSELY ASSOCIATED WITH OBESITY IN NON-DIABETIC INDIVIDUALS. 1,2,3

HUNG HC, 3,4LU FH, 4WU HT, 1,3OU HY, 3,4YANG YC, 3,4WU JS, 3,4CHANG CJ

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. 2The Institute of Basic Medical Sciences of National Cheng Kung University, Tainan, Taiwan. 3College of Medicine, National Cheng Kung University, Tainan, Taiwan. 4Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.

OBJECTIVE Cardiotrophin-1 is known to be a key regulator of energy homeostasis, as well as glucose and lipid metabolism in vivo. However, there are inconsistent results of the association between cardiotrophin-1 and obesity in humans, possibly confounded by hyperglycemia. Therefore, the aim of this study was to investigate the relationships among cardiotrophin-1 levels, overweight and obese individuals without diabetes in a Chinese population.

METHODS The subjects were recruited for the population-based study for chronic diseases conducted in Tainan. Informed consent was obtained from all participants, and the study was approved by the IRB of the National Cheng Kung University Hospital.

RESULTS The median serum cardiotrophin-1 levels were 447.9, 350.6, and 288.1 pg/ml in non-diabetic subjects who were of normal weight (n = 522), overweight (n = 203), and obese (n = 93), UHVSHFWLYHO\ WUHQG WHVW S 6XEMHFWV ZKR ZHUH RYHUZHLJKW DQG REHVH KDG VLJQL¿FDQWO\ ORZHU cardiotrophin-1 levels than those with normal weight. The multivariate linear regression analyses showed that overweight (p < 0.01), obese (p < 0.01), and smoking (p < 0.01) were negatively related to cardiotrophin-1 after adjusting for age, gender, HOMA-IR, hypertension, total cholesterol, HDL, triglyceride, eGFR, ALT, and alcohol drinking.

CONCLUSION The results of this study provided epidemiological evidence that non-diabetic VXEMHFWV ZKR ZHUH RYHUZHLJKW RU REHVLW\ KDG VLJQL¿FDQWO\ ORZHU FDUGLRWURSKLQ FRQFHQWUDWLRQV WKDQ those with normal weight, and both obesity and being overweight were inversely associated with cardiotrophin-1 levels.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

YL

THE RELATIONSHIP BETWEEN SERUM ANGPTL6 AND THE INCIDENCE OF DIABETES IN HUMAN H-Y LI National Taiwan University Hospital, Taipei, Taiwan

The increasing incidence of obesity and type 2 diabetes leads to severe health consequences and ¿QDQFLDO EXUGHQ RI KHDOWK V\VWHPV /LYHU LV UHFRJQL]HG DV DQ HQGRFULQH RUJDQ DQG D WDUJHW RI PHWDEROLF ¿WQHVV WKDW UHOHDVHV KHSDWRNLQHV $QJLRSRLHWLQ OLNH $1*37/ LV NQRZQ WR EH D QRYHO KHSDWRNLQH to regulate body weight and insulin sensitivity. In cross-sectional studies, serum ANGPTL6 were higher in subjects with obesity, metabolic syndrome, and diabetes than in the healthy group. However, cross-sectional studies are limited in its unclear temporal relationship. Since there is no prospective study to investigate the question, we explored if serum ANGPTL6 could predict incident diabetes in a longitudinal cohort in this study. We recruited 1103 subjects without diabetes at baseline. During an average of 4.3 years of follow-up, 113 subjects develop incident diabetes. Serum ANGPTL6 was associated with age, fasting plasma glucose, OGTT 2hr plasma glucose, and hemoglobin A1c, and was higher in male and subjects with pre-diabetes at baseline. Besides, serum ANGPTL6 was associated with the incidence of diabetes (HR for 1SD increase in serum ANGPTL6, 0.77, 95%CI 0.60-0.98, p<0.05), adjusted for age, gender, family history of diabetes, BMI, hemoglobin A1c, HOMA2-B and HOMA2-IR. In conclusion, we found that serum ANGPTL6 is associated with the incidence of diabetes in human.

86

Abstract

SS-1

PRIMARY ALDOSTERONISM IN KOREA JUNG HEE KIM Seoul National University College of Medicine

The first case of PA in Korea was reported in 1968. In the past, hypokalemia was considered to be a prerequisite, and less than 1% of all hypertensive patients were thought to be. However, several cross-sectional and prospective studies have reported prevalence of PA in more than 10% of hypertensive patients. There is no nationwide survey in Korea, but only about 30 cases were only diagnosed in Seoul National University Hospital (SNUH), and unilateral lesions were more dominant than bilateral ones. PA was still underdiagnosed in Korea.

In keeping with recent genetic developments, we performed targeted gene sequencing in 66 patients with APA to detect somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D genes.

Similar to other Asian countries, somatic KCNJ5 mutations were found in 47 (71.2%) of the 66 patients with APA (31 cases of p.G151R and 16 cases of p.L168R). Carriers of somatic KCNJ5 mutations were more likely to be female and young.

The aldosterone-to-renin ratio (ARR) has been introduced as a screening test for PA, but a subtle change in low PRA exaggerates ARR, leading to misdiagnose low-renin hypertension as PA. In Korea, WKH VDOLQH LQIXVLRQ WHVW LV ZLGHO\ XVHG DV D FRQ¿UPDWRU\ WHVW IRU 3$ ZKLFK UHTXLUHV KRVSLWDOL]DWLRQ 7KH captopril challenge test (CCT) can easily performed in outpatient clinics, but the accuracy of it is still FRQWURYHUVLDO 7KHUHIRUH ZH DLPHG WR H[DPLQH WKH FOLQLFDO HI¿FDF\ RI &&7 DV D SRVW VFUHHQLQJ WHVW IRU PA in 64 subjects with suspected PA who had hypertension and ARR > 20. We suggested that subjects with PAC post-CCT at 90 min <13 ng/dL are less likely to have PA, and those with PAC post-CCT at PLQ EXW QJ G/ VKRXOG XQGHUJR VHFRQGDU\ FRQ¿UPDWRU\ WHVWV In PA, adrenal vein sampling (AVS) is recognized as a golden standard method of distinguishing XQLODWHUDO IURP ELODWHUDO GLVHDVHV +RZHYHU $96 LV LQYDVLYH WHFKQLFDOO\ GLI¿FXOW DQG RQO\ DYDLODEOH in several hospitals in Korea. Thus, we developed the clinical prediction parameters as a lateralization marker. Our new clinical prediction parameters included serum potassium, PAC after saline infusion test and unilateral nodule on CT (AUC = 0.779). Patients aged under 35 years with unilateral nodule on CT and hypokalemia may skip the AVS, which was suggested by the Guideline.

In aldosterone-producing adenomas, hyperkalemia after adrenalectomy has been reported due to contralateral zona glomerulosa insufficiency. In SNUH, 13 of 124 patients (10.5%) developed postoperative hyperkalemia. Older age ( > 53 years), longer duration of hypertension ( > 9.5 years), larger mass size on CT ( > 1.95 cm), and impaired preoperative renal function (GFR < 58.2 ml/min) were associated with prolonged postoperative hyperkalemia in patients with APA. The mineralocorticoid receptor (MR) antagonist use did not prevent postoperative hyperkalemia.

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Patients with aldosterone-producing adenomas are treated using surgery, and patients with idiopathic hyperaldosteronism receive medical treatment using MR antagonists. However, the outcomes of surgical and medical treatment for PA remain unclear. Therefore, we compared the outcomes of surgical and medical treatment in 269 patients who were treated for PA. Among patients who were > 60 years old or had impaired renal function, surgical and medical treatment provided similar amelioration of hypokalemia and hypertension. Surgical treatment provided better hypertension and hypokalemia outcomes among patients with PA, compared to medical treatment.

In the future, we may design the Korean nationwide registry for PA, and elucidate the genetic background and prognosis of PA in Korean. Furthermore, the optimal cut-off values for diagnostic testing and noninvasive lateralization markers can be developed.

88

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SS-2

DIAGNOSIS AND PROGNOSIS OF PRIMARY ALDOSTERONISM, TAIWAN-TAIPAI EXPERIENCE VIN-CENT WU, MD, PHD National Taiwan University Hospital,

Given the increasing clinical recognition of primary aldosteronism as public health issue, its heightened risk profile and the availability of targeted surgical/medical treatment. The nationwide SUHYDOHQFH UDWHV RI K\SHUWHQVLRQ GH¿QHG E\ 6%3 ! PP +J RU GLDVWROLF %3 >'%3@ ! PP +J

were 25% in men and 18% in women, and that rate increased to 47% among individuals with age > 60 years. The prevalence of primary aldosteronism (PA) is from 5.5% in normotensive to 16.4% in stage K\SHUWHQVLYH SDWLHQWV %HFDXVH WKH VLJQL¿FDQW FRPSOH[LW\ RI D 3$ GLDJQRVLV UHTXLUHV RQ KHDOWK FDUH resources and even certain special equipment/tests, it is very helpful to have a consensus for patient care. Recently, the Endocrine Society updated its clinical guidelines entitled ‘the management of PA’ in 2016. The Japan Endocrine Society (JES) also developed guidelines because of the high prevalence of cardiovascular disease and the current low case-detection rate of PA in Japan. From a Taiwan Primary Aldosteronism Investigation (TAIPAI) cohort(4), there is a higher prevalence of somatic mutationcarriers among Taiwanese APA patients and there was no gender differences, which are different from other western reports(5, 6). Adrenalectomy decreases long-term all-cause mortality independently for PA patients, while minerocorticoid receptor antagonist treatment may alleviate risk of death only in a U-shape dose. However, an European study showed no difference between surgically and medical treated patients with PA in terms of incidence of cardiovascular accident. The Taiwan Society of Aldosteronism (TSA) task force acknowledges such various nuances and force to accomplish this Taiwan PA consensus at its inauguration meeting, in order to provide update information of internationally acceptable standards, and also to incorporate our local disease characteristics in the management of PA. The consensus is based on evidence medicine and also recognizes the constraints of our real-world clinical practice in managing PA in Asian countries.

It is our hope that the algorithm proposed in this article could further arouse substantial awareness of PA among the medical professionals and the patients, and reconcile its fundamental diagnosis and prognosis.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS1

ADVANCES IN INSULIN AND LIPID MANAGEMENT: GLARGINE U300 AND PCSK-9 INHIBITOR INSULIN GLARGINE U300: THE NEXT GENERATION BASAL INSULIN TO REDEFINE THE LIMITS OF CONTROL CHIA HUNG LIN Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital

,QVXOLQ JODUJLQH 8 *OD ZDV WKH ¿UVW ORQJ DFWLQJ EDVDO LQVXOLQ DQDORJ WR EH LQWURGXFHG into clinical practice and it remains the most widely used. Although Gla-U100 is an effective and safe treatment, there are still many unmet needs in current clinical practice. The higher concentration of LQVXOLQ LQ JODUJLQH 8 *OD UHVXOWV LQ D GLVWLQFW SKDUPDFRNLQHWLF DQG SKDUPDFRG\QDPLF SUR¿OH Gla-U300 has a longer duration of action than U100 and plasma insulin exposure is less variable.

The Phase III EDITION clinical trials indicated that Gla-U300 offers a similar level of glycaemic control to U100 but with a lower rate of hypoglycaemic events, in particular nocturnal episodes.

Patient-level meta-analysis of EDITION 1, 2 and 3 shows the comparable glycemic control with K\SRJO\FHPLD EHQH¿W ZLWK *OD DQG *OD UHJDUGOHVV RI DJH %0, GLDEHWHV GXUDWLRQ DQG eGFR subgroup at baseline. In a real-world assessment of patient characteristics and clinical outcomes of early users of the new insulin Gla-U300 in the US, switching to Gla-300 from other basal insulins was associated with improved glycemic control and a trend towards less hypoglycemia in patients with T2DM after 6 months.

Through the upcoming symposium, we will be sharing “real world” case studies of local Taiwan clinical experiences with the next generation insulin Gla-U300, including T2DM patients on Gla-U300 switched from OADs uncontrolled, and other basal insulin uncontrolled.

Taken together, the data suggests that Gla-U300 represents an overall better treatment option.

While Gla-U300 and Gla-100 exhibit equally strong efficacy, more importantly, Gla-U300 with its VDIHU DQG PRUH VWDEOH EORRG JOXFRVH FRQWURO SUR¿OH SURYLGHV 7DLZDQ +&3V DQG SDWLHQWV WKH FRQ¿GHQFH WR DWWDLQ PRUH RSWLPDO JO\FHPLF JRDOV WKURXJK UHGH¿QLQJ WKH OLPLWV RI )3* FRQWURO

90

Abstract

LS1

PCSK-9 INHIBITOR:OPTIMAL TREATMENT IN LIPID CONTROL ߚ࢔୊ ‫ݎٴ‬ख‫܉‬ᚃଲЗ᠛ϲऌ

The risks of cardiovascular (CV) disease and mortality rise in association with increasing lowGHQVLW\ OLSRSURWHLQ FKROHVWHURO /'/ & OHYHO 'HVSLWH WKH HI¿FDF\ RI D YDULHW\ RI SULPDU\ RU VHFRQGDU\ preventive therapies, patients who have had atherosclerotic events or diabetes with risk factors remain at high risk for the occurrence of CV events. Meta-analysis combined prospective clinical studies have shown that lowers LDL-C substantially reduces the incidence of IHD and decreases major CV events incidence. International guidelines, ex. European Society of Cardiology, as well as Taiwan Lipid Guideline, hence, also recommend to treat to LDL-C level below 70mg/dL for very high CV risk patients, such as documented MI, PCI, CABG, arterial revascularization procedures…etc. and could consider to further lower LDL-C level below 55mg/dL for patients with acute coronary syndrome combining with diabetes.

Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is effective in lipid lowering and reducing cardiovascular mortality by preventing myocardial infarction and ischemic stroke. However, LDL-C goal attainment rates for CV high risk populations DUH TXLWH VXERSWLPDO 7KH SRVVLEOH UHDVRQV LQFOXGH WKH OLPLW RI VWDWLQ HI¿FDF\ IRU &9 KLJK ULVN SDWLHQWV and patients with familial hypercholesterolemia to reach treatment targets, statin intolerance or fear of side effects caused by statin…

Alirocumab is a recently launched lipid lowering monoclonal antibody with novel mechanism, PCSK9 inhibitor. PCSK9 is an abbreviation for proprotein convertase subtilisin/kexin type 9 and mainly expressed and secreted in the liver. It plays an important role in the control of LDL-C levels by binding LDL receptor (LDLR) on the cell surface, promoting degradation of LDLR in the lysosome DQG EORFNLQJ WKH UHF\FOH RI /'/5 WR WKH SODVPD PHPEUDQH $OLURFXPDE¶V FOLQLFDO HI¿FDF\ DQG VDIHW\ are proved by more than 10 large-scale international phase III trials. Regarding LDL-C lowering power on top of statins, Alirocumab delivers sustained 50-60% additional LDL-C reductions over the duration of studies. Safety profile is generally comparable to placebo and has low potential for drug interaction regardless of diabetes status. Mean HbA1c and fasting plasma glucose measurements are also comparable between Alirocumab and control groups over 52 weeks of treatment. A posthoc analysis of ODYSSEY study further showed a significant lower rate of adjudicated major CV events with Alirocumab. Based on currently available clinical evidence, Alirocumab is represent new options of lipid lowering therapy in hypercholesterolemia patients with or without atherosclerosis cardiovascular diseases to further effectively reduce recurrent ischemic events.

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LS2

EXPERIENCE OF SHARED MEDICAL APPOINTMENTS IN TAIWAN 1

BONIFACE J. LIN, 2PEI-FEN LEE

1.

Honorary consultant, Cardinal Tien Hospital. 2.Graduate student, National Taipei University of Nursing and Health Sciences.

Shared Medical Appointment is also known as a group outpatient clinic. Dr. Joseph Pratt of the Massachusetts General Hospital in 1905 developed a group outpatient treatment for tuberculosis patients. Dr. Pratt asked the patient every day to record the weight at home and the number of hours of sleep while breathing fresh air in the backyard or balcony. Once a week in the group outpatient clinic (classroom), Dr. Pratt let the patients to compare the notes with each other, and posted the best note. Soon the patents began competing with each other and the cure rate for these poor tuberculosis patients at home became comparable with that obtained by the rich patients who lived in the expensive mountain sanatorium. In the 1920s, Dr. Pratt also used the same group method to help patients with SV\FKRQHXURVLV 6LQFH WKHQ JURXS WKHUDS\ ZDV DSSOLHG LQ PDQ\ ¿HOGV RI SV\FKLDWU\ $ERXW \HDUV ago, Shared Medical Appointments were gradually applied in a variety of chronic diseases such as GLDEHWHV KHDUW IDLOXUH DQG DVWKPD ZLWK VLJQL¿FDQW HIIHFWV Implementation process and method: In June 2015, we began to try this innovative model.

Each time 7 to 12 patients and a few family members attended the SMA. Medical staff tried to avoid delivering lectures, mainly to let patients share the experience and ideas, learn from each other to really understand their own problems, and also enhance the ability of patients to solve the problem. In the ¿UVW KDOI RI HDFK VHVVLRQ ZH XVHG RSHQ TXHVWLRQV WR JXLGH WKH SDWLHQW WR IRUPXODWH WKHLU RZQ TXHVWLRQV We usually had enough time left to discuss one of the 9 items of self-management courses developed at Wilfordhall Medical Center in Texas. In our SMA, a nurse educator led the patient discussion, and a dietitian and a physician joined at any time to participate in the discussion. When the physician is not needed in the discussion, the physician is invited to examine and write prescriptions to one patient at a time at a corner of the discussion room. In order to respect the privacy of each patient, we let HYHU\RQH SUHVHQW WR VLJQ D FRQ¿GHQWLDO FRQVHQW IRUP HDFK WLPH 7KH DYHUDJH QXPEHU RI SDWLHQWV ZKR participated once per month increased from 26 to 89 persons. Of 68 patients who participated in more than 4 months, 87.3% of A1C attained <7%, 64.7% of BP <130/80 mmHg, 76.5% of LDL-C <100 mg / dL, and 42.6% of patients attained the goals of ABC. Eighty three % of patients agreed that SMA was helpful.

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LS3

UPDATE IN GOUT MANAGEMENT: FROM VIEWPOINT OF TOTAL CARE OF METABOLIC SYNDROME 1

T-Y HSIEH, 1D-Y CHEN, 2I-T LEE, 3WAYNE H-H SHEU.

1

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.

Metabolic syndrome, which consists of multiple interrelated conditions, increases the risk for atherosclerotic cardiovascular disease up to 3 times and increases the risk for type 2 diabetes up to 5 times. Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease.

7KH SRWHQWLDO OLQN EHWZHHQ JRXW D FRPPRQ LQÀDPPDWRU\ DUWKULWLV DQG PHWDEROLF V\QGURPH KDV been repeatedly suggested, but no quantitative population data are available; therefore, the magnitude of the problem remains unclear. The proposed connection has been supported by the close association between hyperuricemia and insulin resistance syndrome Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular GLVHDVHV DQG VKRZHG HYLGHQFH RI WKHUDSHXWLF EHQH¿W LQ XULF DFLG ORZHULQJ WKHUDS\ LQ GLDEHWHV SDWLHQWV These findings indicate that the prevalence of metabolic syndrome is remarkably high among individuals with gout. Given the serious complications associated with metabolic syndrome, this frequent comorbidity should be recognized and taken into account in long-term treatment and overall health of individuals with gout. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases.

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MOSA1C, A MULTINATIONAL OBSERVATIONAL STUDY ASSESSING INSULIN USE: UNDERSTANDING THE CHALLENGES ASSOCIATED WITH THE PROGRESSION OF THERAPY ֕‫܇‬ᐆ ፐҢᆌւഌᚗ‫ڸ‬ᚃଲ

Healthcare professionals (HCPs) and their patients consider conversations about intensifying LQVXOLQ WKHUDS\ DV GLI¿FXOW DQG FKDOOHQJLQJ %XW ZK\" 7UXWK EH WROG SDUW RI WKH UHDVRQ PD\ EH WKDW WKH EDUULHUV WR LQVXOLQ LQWHQVL¿FDWLRQ DUH FXUUHQWO\ QRW ZHOO XQGHUVWRRG ,Q RUGHU WR RYHUFRPH SRWHQWLDO barriers both from the HCP and the patient perspective, they needed to first be identified and then followed over years of patients’ treatment experience. That’s what inspired the MOSA1c study.

MOSAIc is a multinational, non-interventional, prospective, observational cohort study designed WR SURYLGH DQ XQGHUVWDQGLQJ RI WKH VSHFL¿F FKDOOHQJHV DVVRFLDWHG ZLWK SURJUHVVLRQ RI LQLWLDO LQVXOLQ therapy, from both the patient’s and the physician’s perspective. Its primary objective is to determine if the characteristics of the patient, physician, and healthcare system affect progression from initial insulin therapy.

The study cohort consists of more than 4300 adults with type 2 diabetes, from 18 countries, 5 geographic regions (Asia, Europe, North America, Latin America and the Middle East) during 2-year study period. Patients on initial insulin therapy (basal insulin alone or insulin mixtures) for at least 3 months, with or without any combination of oral agents, were eligible for the study.

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LS5

CLINICAL DETERMINANTS AND CHARACTERISTICS DRIVING CLINICAL DECISION IN ELDERLY T2DM MANAGEMENT C-H CHU Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan, R.O.C.

Diabetes population has increased rapidly and was estimated to reach 642 million patients in IURP PLOOLRQ LQ ZLWK ZHVWHUQ SDFL¿F EHLQJ WKH PRVW SUHYDOHQW DUHD $ WUHQG WRZDUG higher prevalence of type 2 diabetes (T2D) in older individuals across gender and ethnicity has also been reported. International T2D management guidelines have supported an individualized approach, considering age, body weight, comorbidities, and diabetes duration, to achieve better diabetes care.

However, T2D in ageing communities associated with different underlying pathophysiology and higher risk of micro- and macro-vascular complications pose a unique challenge in clinical setting.

This symposium will overview the current ageing state of T2D in Taiwan, discuss new emerging challenges, including frailty, sarcopenic obesity, and cognitive impairment, and summarize the clinical characteristics driving therapeutic decisions which should be considered. A multidimensional and multidisciplinary assessment process is essential to obtain information on medical, psychosocial, and functional capabilities, and also on how impairments of these functions could limit activities.

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LS6

THE ROLE CO-MORBIDITIES PLAY IN THE CHOICE OF ANTIHYPERGLYCEMIC AGENTS FOR PATIENTS WITH TYPE 2 DIABETES LIN, CHING-LING Department of Metabolism & Endocrinology, Cathy General Hospital

OBJECTIVE The management of patients with type 2 diabetes has become more complex in UHFHQW \HDUV ,Q JHQHUDO WKH IRXQGDWLRQDO XVH RI PHWIRUPLQ DQG OLIHVW\OH LQWHUYHQWLRQV KDV VLPSOL¿HG clinicians' selection of initial therapy for most patients. However, eventually, it is conceivable that more medication will be needed in addition to metformin glycemic management with the progressive nature of type 2 diabetes. One of the challenges of T2DM management is the increasing extent of comorbidity. Most adults with diabetes have at least one morbid chronic disease, and 40% have three or more. The importance of treating patients with T2DM to target glycemic levels applies to patients with and without comorbidities in the same way. However, evidence-based diagnostic and treatment strategies should take comorbidities as treatment consideration. A position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) has suggested individualized and tailored care for T2DM, taking into account several elements, including comorbidities. The diabetes management has also moved from being “gluco-centric” to “patientcentric.” The last two decades have witnessed the development of a wide variety of new therapeutic options to treat T2DM. Although each class of these agents broadly shows similar efficacy as monotherapy with hardly any clinically meaningful differences in glucose-lowering potency at least in VKRUW WHUP HDFK WKHUDSHXWLF FODVV KDV GLVWLQFW DGYHUVH HYHQW SUR¿OH WKDW HLWKHU FRXOG EH UHODWHG WR WKHLU VSHFL¿F PHFKDQLVP RI DFWLRQ DQG RU SRWHQWLDO RII WDUJHW HIIHFWV 7KH VWHS XS VWUDWHJLHV DIWHU PHWIRUPLQ monotherapy most widely used in community medicine are either addition of a sulphonylurea or addition of a dipeptidylpeptidase-4 inhibitor or others. Recently, Sodium glucose transporter 2 inhibitors (SGLT2I) are also becoming one of the new second line choices after metformin. Despite WKH &9 EHQH¿W RXWFRPH IURP RQH WULDO IRU RQH RI WKH 6*/7 LQKLELWRUV VHYHUDO $( LVVXH KDV DOVR EHHQ raised for usage with caution, especially in patients with more comorbidity, such as elderly or CKD SDWLHQWV 7KHUHIRUH LQ DGGLWLRQ WR WKH JO\FHPLF FRQWURO WKH ULVN DQG EHQH¿W HYDOXDWLRQ IRU LQGLYLGXDO diabetic patients should be carefully considered. It is noteworthy that incretin-based therapies (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) have become fundamental treatment options for WKHLU HI¿FDF\ DQG VDIHW\ SUR¿OHV IRU WKH ODVW GHFDGH '33 LQKLELWRUV EHORQJLQJ RQH RI 2+$V DQG acting in inhibition of DPP4 on the incretin system to regulate glucose homeostasis, are useful in the management of patients with T2DM over the spectrum of A1C levels, including drug-naive patients as well as those treated with other glucose-lowering therapy. Sitagliptin, one of the DPP4 inhibitors has been shown with well-tolerated in broad T2DM patient type, including renal impairment and elderly 96

Abstract

patients. These special population patients are usually with more comorbidity to increase the challenge for the glycemic control. In addition, from recent CV safety trails data, Sitagliptin is also proven without increase CV risk in T2DM with CVD, even in the elderly or CKD patient subgroup analysis.

Since T2DM is a progressive disease, an important therapeutic issue is to ensure that each stage of treatment is as effective as possible to delay escalation of treatment intensity to the next line of treatment as long as possible. The comorbidities of T2DM patients, especially in special populations, needs to be carefully considered for their treatment options. . Maintaining a patient on an unchanged treatment is a pragmatic outcome criterion which combines notions of both effectiveness and tolerability.

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LS7

THE GROWING EVIDENCE OF NEW PERSPECTIVES IN TYPE 2 DIABETES TREATMENT - SGLT2 INHIBITOR AND ITS ADDITIONAL EFFECTS PROFESSOR WASIM HANIF MBBS, MD, FRCP Professor of Diabetes & Endocrinology University Hospital Birmingham UK

OBJECTIVE: The prevalence of type 2 diabetes is increasing across the globe. The ADA/EASD JXLGHOLQHV IRU WKH PDQDJHPHQW RI GLDEHWHV UHFRPPHQG 0HWIRUPLQ DV WKH GUXJ RI ¿UVW FKRLFH LQ WKH treatment algorithm. After Metformin, nearly all the available drugs can be used depending upon the individual patients. There is a lot of emphasis on individualization of care but with no clear guidelines on how the individualization should be based. The data from a number of countries suggest that the second choice of therapy after Metformin is either Sulphonylureas or DPP-4 inhibitors. The recent trials data including the CV outcome studies suggest that perhaps the SGLT-2 inhibitors are better VXLWHG ERWK IURP HI¿FDF\ DQG RXWFRPH SRLQW RI YLHZ WR EH XVHG HDUO\ RQ LQ WKH WUHDWPHQW DOJRULWKP as second line agents. This scholastic presentation goes through the RCT evidence for the early use of SGLT-2 inhibitors in the type 2 diabetes algorithms. It also presents the latest real world data from WKH 8. &35'6 ORRNLQJ DW WKH HI¿FDF\ GXUDELOLW\ DQG VDIHW\ RI 'DSDJOLÀR]LQ ,W DOVR FRYHU WKH &9 RXWFRPH GDWD RI 'DSDJOLÀR]LQ WKDW KDV EHHQ UHFHQWO\ SXEOLVKHG E\ 3URIHVVRU +DQLI¶V JURXS IURP WKH THIN database of UK.

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LS8

PATHOGENESIS AND TREATMENT IN PATIENTS WITH DIABETIC NEPHROPATHY YASUHIKO TOMINO, MD, PHD Professor Emeritus, Juntendo University, Tokyo, Japan 0DQDJLQJ 'LUHFWRU $VLDQ 3DFL¿F 5HQDO 5HVHDUFK 3URPRWLRQ 2I¿FH &KLHI 0HGLFDO &RUSRUDWLRQ 6+2:$.$, Tokyo, Japan

As reported by the Japanese Society of Nephrology (JSN), 13.0 million people have chronic kidney disease (CKD). In Japan, major causes of end stage kidney disease (ESKD) are type 2 diabetic nephropathy (diabetic kidney disease), chronic glomerulonephritis, mainly IgA nephropathy, and hypertensive nephrosclerosis. I would like to focus on the pathogenesis and treatment of patients with diabetic nephropathy.

1. Pathogenesis of diabetic nephropathy The initiation and progression factors of diabetic nephropathy have included genetic factors and/or environmental factors such as lifestyle impairment, i.e. a high protein and/or high salt diet, smoking and obesity. Advanced glycation end products (AGEs) may stimulate the growth factors DQG RU F\WRNLQHV VXFK DV 7*)ȕ DQG SURGXFH DQG DFFXPXODWH H[WUDFHOOXODU PDWULFHV (&0 VXFK as fibronectin, type IV collagen, and laminin in the glomeruli of diabetic nephropathy patients.

0LFURLQÀDPPDWLRQ DQG DFWLYDWLRQ RI UHDFWLYH R[\JHQ VSHFLHV 526 PD\ DOVR SOD\ DQ LPSRUWDQW UROH in the progression of diabetic nephropathy. Although renal biopsy is not performed on all patients with GLDEHWHV IRU D GH¿QLWH GLDJQRVLV FOLQLFDO GLDJQRVWLF FULWHULD DUH RIWHQ XVHG LQ -DSDQ $PRQJ WKHP WKH presence of diabetic retinopathy and/or neuropathy are important findings for clinical diagnosis. In -DSDQ D QHZ GLDEHWLF QHSKURSDWK\ FODVVL¿FDWLRQ ZDV DGDSWHG WR WKH &.' FODVVL¿FDWLRQ E\ WKH -61 and JSD (the Japan Diabetes Society). From new biomarkers using urine and serum samples, Gohda et al. (J Am Soc Nephrol 2012; 23: 516-524 and 507-515, Curr Diab Rep 2013; 13: 560-566) reported that the concentrations of transforming necrosis factor receptors (TNFRs) strongly predict early and late renal function loss in both type 1 and 2 diabetes, independent of classical risk factors such as JORPHUXODU ¿OWUDWLRQ UDWH *)5 DQG DOEXPLQXULD 2. Treatment of diabetic nephropathy Despite the successful application of lifestyle changes, metabolic control (blood glucose: less than HbA1c of 7.0 % , LDL-C: less than 100 or 120 mg/dL), and blood pressure control (blood pressure: less than 130/80 mmHg) using ACE inhibitors and ARB, residual renal risk remains very high, leaving the diabetic population with a clear need for novel treatments. There are many therapeutic strategies to address the clinical condition, as follows: 1) adequate exercise and a low protein diet (decrease of dietary protein intake according to renal function), 2) AGE inhibitors, 3) statins, 4) eicosapentaenoic

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acid (EPA), 5) renin angiotensin system blockers (ARBs), and 6) a vitamin D analogue (Kidney Blood Press Res 2014; 39: 450-489). We usually use DPP (dipeptidyl peptidase)-4 inhibitors for patients with type 2 diabetes. It is generally thought that the activated GLP (glucagon-like peptide)-1 by the LQKLELWLRQ RI '33 DFWLYLW\ PD\ LPSURYH WKH LQKLELWLRQ RI JOXFDJRQ H[FUHWLRQ IURP SDQFUHDWLF Į FHOOV DQG LQFUHDVH LQVXOLQ H[FUHWLRQ IURP SDQFUHDWLF ȕ FHOOV *DVWURHQWHURORJ\ 7KH sodium-glucose co-transporter 2 (SGLT2) inhibitor, i.e. a new class of diabetic medications, is used RQO\ IRU WKH WUHDWPHQW RI W\SH GLDEHWHV 6*/7 LV D ORZ DI¿QLW\ KLJK FDSDFLW\ JOXFRVH WUDQVSRUWHU located in S1 segment of the proximal tubule in the kidneys. It is responsible for 90 % of glucose reabsorption. Inhibition of SGLT2 leads to the decrease of blood glucose levels due to the increase in renal glucose excretion. It is necessary to treat common advanced stage CKD patients, including diabetic nephropathy patients, using an oral carbonaceous adsorbent (AST-120, KremezinR) from an early stage for a long duration in order to inhibit the progression to ESKD. It consists of black spherical particles 0.2-0.4mm in diameter. Composed mainly of carbon (approximately 96%), AST-120, exhibits a superior adsorption-ability for certain acidic and basic organic compounds that are known to be increased in renal failure patients.

Although the current treatments remain suboptimal, further clinical trials are needed to identify novel therapies for patients with diabetic nephropathy.

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LS9

CLINICAL APPLICATION OF GLP-1 RA ARE THERE ANY PREDICTORS OF EFFICACY FROM CLINICAL TRIALS? ҥസϧ Ҙஷ‫ۊ‬जᚃଲϲϸ‫ུݫ‬ചхᗃऌ

Multiple new classes of diabetes treatment have emerged in the recent decade to tackle this complicated disease. This could confuse even the most experienced doctors in choosing between these new therapies. Type 2 diabetes management emphasizes the importance of individualized therapy, which should takes into account both the patient’s clinical condition and preferences. Understanding WKH GLIIHUHQFH EHWZHHQ HI¿FDF\ DQG HIIHFWLYHQHVV ZLOO KHOS SK\VLFLDQV ZHLJKW LQ KRZ WKH GLIIHUHQFHV LQ therapies affect patients.

Glucagon-like peptide-1 agonists are emerging as useful treatments since they not only lower EORRG VXJDU EXW DUH DOVR DVVRFLDWHG ZLWK H[WUD JO\FHPLF EHQH¿W LQFOXGLQJ ZHLJKW FRQWURO DQG DOVR ORZ risk of hypoglycemia.

Dulaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Dulaglutide safety and glycemic efficacy have been previously demonstrated in the AWARD clinical trial program.

7KLV SUHVHQWDWLRQ ZLOO DLP WR VKDUH WKH XSGDWHG LQIRUPDWLRQ RQ HIIRUW WR ¿QG HI¿FDF\ SUHGLFWRUV based on major patient baseline characteristics in response in the sub-analysis of data from the AWARD clinical trial program. This will help physicians make informed decision when choosing different types of therapies to help patient reach their goal.

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LS10

CLINICAL INTERPRETATION OF PHARMACOKINETICS AND PHARMACODYNAMICS PROFILE OF BASAL INSULIN ANNE DORNHORST Department of Medicine, Imperial College Healthcare NHS Trust

Glycaemic fluctuations in healthy people are tightly controlled by a number of physiological homeostatic mechanisms. For patients with type 1 and type 2 diabetes, basal insulin therapy is essential to control blood glucose level by restricting excessive hepatic glucose production in the context of insulin resistance in both the liver and the peripheral tissues, decreased insulin secretion, and excess glucagon secretion. In addition, fasting plasma glucose variability is reportedly associated with the 10-year survival of diabetes patient, with both intra-day glucose variability and HbA1c variability being independent risk factors for microangiopathy. Therefore, glucose variability may be an additional risk factor for diabetic complications, independent of hyperglycemia. Ideal basal insulin is to ensure continuous insulin coverage throughout the 24 hrs of the day with flat and predictable glucose lowering effect. As albumin binding molecules of Insulin detemir (IDet) and degludec (IDeg), OHDGLQJ WR D ÀDW DQG VWDEOH DFWLRQ SUR¿OH DW VWHDG\ VWDWH LV LPSRUWDQW IRU FOLQLFDO HYDOXDWLRQ DW LQLWLDWLRQ and titration of treatment to achieve blood glucose control target.

102

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LS11

NOVEL STRATEGIES FOR IMPROVING LONG-TERM OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES S KASPERS Boehringer Ingelheim, Corporate, Ingelheim, Germany

Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk based on the study results with intensive glycemic control. On the other hand, following a request of the US Food and Drug Administration, many large CV outcome studies have been performed in patients with longstanding disease and established CV disease to demonstrate safety of newer glucoselowering agents (saxagliptin, alogliptin, sitagliptin, lixisenatide) but did not show superiority in the CV outcomes compared with placebo.

By contrast, in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study, CV death, all-cause mortality, and hospitalization for heart failure were significantly decreased when empagliflozin was added instead of placebo to therapy for patients with high CV risk and T2DM already well treated with statins, glucose-lowering drugs, and blood pressure-lowering drugs as well as antiplatelet agents. Even though sodium–glucose cotransporter 2 inhibitors (SGLT2i) exert multiple metabolic benefits (decreases in HbA1c, body weight, and blood pressure and an increase in HDL cholesterol), all of which could reduce CVD risk, LW LV XQOLNHO\ WKDW WKH UHGXFWLRQ LQ &9 PRUWDOLW\ FDQ EH H[SODLQHG E\ HPSDJOLÀR]LQ¶V PHWDEROLF HIIHFWV More likely, hemodynamic effects, specifically reduced blood pressure and decreased extracellular volume, are responsible for the reduction in CV mortality and heart failure hospitalization.

Coincidentally, the CV outcome study with liraglutide (LEADER) also demonstrated a significant reduction of the composite endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal VWURNH %RWK RI VWXGLHV JDYH D QHZ KRSH IRU IXUWKHU EHQH¿FLDO WUHDWPHQW RSWLRQV IRU 7 '0 SDWLHQWV with established CVD. Therefore, the latest updated guidelines in diabetic treatments recommend that adding HPSDJOLÀR]LQ RU OLUDJOXWLGH DV D FRQVLGHUDWLRQ IRU 7 '0 SDWLHQWV ZLWK FDUGLRYDVFXODU GLVHDVH WR UHGXFH cardiovascular and all-cause mortality.

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LS12

THE ADVANCED APPLICATION OF CONTINUOUS GLUCOSE MONITORING (CGM) FROM MONITORING TO DIAGNOSIS 1

CHIA-HUNG LIN

1

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

In ‘‘professional’’ continuous glucose monitoring (CGM), the device is owned and controlled by medical professionals and patients receive no information while wearing the device. Since there are either minimal behavior changes or none at all in response to the results of professional CGM, this method is more likely to observe the patients’ actual glucose excursions. Results can be determined in D FOLQLFLDQ¶V RI¿FH DQG JUDSKHG SURYLGLQJ XVHIXO LQIRUPDWLRQ LQFOXGLQJ WKH H[WHQW RI ZLWKLQ GD\ DQG between day variations in blood glucose, and the frequency of unrecognized hypoglycemia.

7KH LGHQWL¿FDWLRQ RI JOXFRVH SDWWHUQ LQ GLDEHWLF VXEMHFWV UHFHLYLQJ LQVXOLQ WKHUDS\ LV VRPHWLPHV GLI¿FXOW 7KH UHVXOWV RI SURIHVVLRQDO FRQWLQXRXV JOXFRVH PRQLWRULQJ FDQ LPSURYH WKH LGHQWL¿FDWLRQ RI different pattern in diabetic treatment. The mean amplitude of glucose excursion (MAGE), nocturnal high glucose, and nocturnal low glucose are highly associated with the development of diagnostic algorithms. The latest CARELINK® iPRO® PATTERN SNAPSHOT is available in the clinical practice. The combinations of currently guidelines and clinical trials, prioritizing patterns and possible causes could be listed automatically. How to use clinical judgment to determine the appropriateness of the ranked order and possible causes is a upcoming issue in the education and training of CGM. In conclusion, professional continuous glucose monitoring can be used as not only monitoring EXW DOVR D XVHIXO WRRO WKDW LPSURYHV LGHQWL¿FDWLRQ RI JOXFRVH SDWWHUQV DPRQJ GLDEHWLF SDWLHQWV UHFHLYLQJ variated therapy.

104

Abstract

OD-01

THE ROLES OF ADIPOSITY ON INSULIN RESISTANCE, GLUCOSE EFFECTIVENESS, FIRST AND SECOND PHASE IN AGED SUBJECTS 1

DEE PEI, 2JIUNN-DIANN LIN, 3YEN-LIN CHEN, 2CHUNG-ZE WU, 1TE-LIN HSIA

1

Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.; 2Division of Endocrinology, Department of Internal Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 3Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.

Aims: The aim of study is to evaluate the relative influence of body mass index (BMI) on insulin UHVLVWDQFH ,5 WKH ¿UVW )3,6 DQG VHFRQG SKDVH LQVXOLQ VHFUHWLRQ 63,6 DQG JOXFRVH HIIHFWLYHQHVV *( DW D QRUPDO ¿[HG SODVPD JOXFRVH OHYHO LQ ROG VXEMHFWV Methods: In total, we enrolled 265 individuals with the same fasting plasma glucose level 5.56 mmol/l and same age 60 years old. In this way, the effects of both confounders could be adjusted. Their body mass index ranged (BMI) between 20.0-34.2 kg/m2. IR, FPIS, SPIS and GE were estimated by the equations we built previously. Since the units of the correlation lines are different, the absolute units of these four factors were transformed to relative units, the percentage. Thus, they can be compared.

Results: 6LJQL¿FDQW FRUUHODWLRQV ZHUH REVHUYHG EHWZHHQ %0, DQG )3,6 63,6 ,5 DQG *( LQ ERWK JHQGHUV which were higher those reported previously. For men, SPIS is most profoundly affected by the BMI, followed by IR, FPIS and GE. For women, the order is a slightly different from that of the men, the RUGHU LV ,5 63,6 )3,6 DQG *( 7KHUH LV D VLJQL¿FDQW GLIIHUHQFH EHWZHHQ DOO WKHVH VORSHV H[FHSW IRU the slopes between FPIS and SPIS in women (p = 0.534) and between IR and FPIS in men (p = 0.258).

Conclusions: The contribution of the obesity to these factors except GE were higher than that those reported previously. The BMI has the most profound effect on insulin secretion in men and on IR in women in this old cohort.

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OD-02

MAJOR URINARY PROTEIN 1 INTERACTS WITH CANNABINOID RECEPTOR TYPE 1 IN FATTY ACID-INDUCED HEPATIC INSULIN RESISTANCE IN A MOUSE HEPATOCYTE MODEL 1

CHIN-CHANG CHEN, 2CHING-FAI KWOK, 3YUNG-PEI HSU, 4KUANG-CHUNG SHIH, 5YAN-JIE LIN, 2,3LOW-TONE HO 1

Division of Urology, Department of Surgery, Chang Gung Memorial Hospital Linkou, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.; 3Department of Medical Research, Taipei Veterans General Hospital, Taiwan, R.O.C.; 4Department of Medicine-Metabolism, Cheng Hsin General Hospital, Taiwan, R.O.C.; 5Department of Research Planning and Development, National Health Research Institutes, Taiwan, R.O.C.

Hepatic insulin resistance (HIR) is a metabolic abnormality characterized by increased gluconeogenesis which usually contributes from an elevation of free fatty acids. Cannabinoid receptor type 1 (CB1R) and major urinary protein 1 (MUP1) are thought to play pivotal roles in mitochondrial dysfunction, liver steatosis and insulin resistance. The aim of this study was to explore the role of MUP1 in CB1R-mediated HIR through the dysregulation of mitochondrial function in AML12 mouse hepatocytes challenged with high concentration of free fatty acids (HFFA). Firstly we observed that treatment of AM251, a selective CB1R antagonist, obviously reversed the HFFA-induced reduction of MUP1 protein expression both in vivo and in vitro. Additionally, our results revealed that AM251 also reverted HFFA-mediated decrease of the mRNA level of mitochondrial biogenesis-related factors, mtDNA amount, ATP production, mitochondrial respiratory complexes-I and-III, and mitochondrial membrane potential, thus consequently might correlate with a parallel reduction of ROS production.

Meanwhile, AM251 attenuated HFFA-induced impairment of insulin signaling phosphorylation and elevation of phosphoenolpyrvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), two key enzymes of gluconeogenesis. Silence of MUP1 gene abolished the inhibitory effect of AM251 on HFFA-mediated elevation of PEPCK and G6Pase expression, whereas the suppression of insulin signaling and mRNA level of mitochondrial biogenesis-related factors were only partially recovered. $OWRJHWKHU WKHVH ¿QGLQJV VXJJHVW WKDW WKH DQWL +,5 HIIHFW RI $0 YLD LPSURYHPHQW RI PLWRFKRQGULDO functions might occur in a MUP1-dependent manner.

106

Abstract

OD-03

ASSOCIATION OF ANTIHYPERGLYCEMIC AGENTS AND GUT MICROBIOTA IN TYPE 2 DIABETES MELLITUS WEI-WEN HUNG, WEI-CHUN HUNG, YI-CHUN TSAI, HE-JIUN JIANG, SHYI-JANG SHIN, PI-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 Type 2 diabetes mellitus is one of the most prevalent disease in the modern era and cause a great threat to our health due to its multiple chronic diabetic complications. Recent studies suggest the impact of gut microbiota on metabolic functions. In addition, drug is one of the most FRPPRQ IDFWRUV LQÀXHQFLQJ JXW PLFURELRWD FRPSRVLWLRQ 7KXV ZH DLPHG WR VWXG\ WKH DVVRFLDWLRQ RI antihyperglycemic agents and gut microbiota in type 2 diabetes mellitus.

MATERIALS AND METHODS Patients with type 2 diabetes mellitus were recruited from the outpatient clinic in an university hospital. The present analysis was done based on 44 participants diagnosed with type 2 diabetes mellitus. We used 16S rRNA gene sequencing to analyze the fecal microbiota. Student’s t-test was used as statistical analysis. Based on the usage of antihyperglycemic agents, we compared the difference of gut microbiota with or without metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitor, and insulin. RESULTS We found an association between usage of antihyperglycemic agents and gut microbiota. Dipeptidyl peptidase-4 inhibitor was associated with higher relative abundance of Clostridium leptum group, while sulfonylureas and insulin were associated with less genus Bacteroides and less genus Bifidobacterium, respectively. There were no statistical differences observed with Faecalibacterium prausnitzii, phylum Firmicutes, or phylum Bacteroidetes with or without metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitor, and insulin.

DISCUSSION Our data proved the association of certain antihyperglycemic agents and gut microbiota in type 2 diabetes mellitus. Further research is needed to clarify the impact of gut microbiota on glycemic status and evaluate the cause-effect relationship between glucose metabolism and gut microbiota. In the future, gut microbiota has the potential to serve as a new therapeutic tool or target in treating type 2 diabetes mellitus.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-04

INPATIENT SCREEN OF RETINOPATHY PREDICTING LONG-TERM MORTALITY IN THE DIABETIC PATIENTS WITHOUT ALBUMINURIAAN OBSERVATIONAL STUDY 1

I-TE LEE, 1YA-MEI HSIEH

1

Taichung Veterans General Hospital

Aims: There is a high hospitalization rate in the subjects with diabetes mellitus. Since retinopathy and albuminuria are both important manifestations of microvascular diseases in diabetes, we aimed to investigate the effect of retinopathy and albuminuria on long-term mortality in diabetic inpatients in this observational cohort study.

Materials and Methods: Diabetic inpatients with a primary diagnosis of poor glucose control were consecutively enrolled during hospitalization. Clinical information was collected by review of medical records and mortality data were obtained from the national registry in Taiwan.

Results: A total of 779 diabetic inpatients were included in the study. Over a median followup period of 6.7 years (interquartile range, 4.1–9.6 years), there were 412 (52.9%) subjects who died during the study. Patients with albuminuria has highest risk of mortality (HR = 2.600, 95%CI = ௅ 3 LQ FRPSDULVRQ WR WKRVH ZLWKRXW DOEXPLQXULD DQG UHWLQRSDWK\ $PRQJ SDWLHQWV without albuminuria, those with retinopathy had higher risk of mortality (HR = 1.633, 95% CI = ௅ 3 WKDQ WKRVH ZLWKRXW UHWLQRSDWK\ +RZHYHU DPRQJ SDWLHQWV ZLWK DOEXPLQXULD WKHUH ZDV QR VLJQL¿FDQW GLIIHUHQFH LQ ULVN RI PRUWDOLW\ EHWZHHQ WKRVH ZLWK DQG ZLWKRXW UHWLQRSDWK\ 3

7KH HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH ZDV DQ LQGHSHQGHQW SUHGLFWRU RI PRUWDOLW\ CI = ௅ 3 = 0.001) but not retinopathy in diabetic inpatients with albuminuria.

Conclusions: Albuminuria is a strong predictor of long-term mortality in diabetic inpatients after discharge. Retinopathy is an independent predictor of mortality in diabetic inpatients without albuminuria, but not in those with albuminuria. Low estimated glomerular filtration rate is a better predictor of mortality than retinopathy in diabetic inpatients with albuminuria.

108

Abstract

OD-05

INCIDENCE OF CHRONIC KIDNEY DISEASE IS RELATED WITH HYPERTRIGLYCERIDEMIA IN TYPE 2 DIABETES PATIENTS - A PROSPECTIVE COHORT STUDY IN A COMMUNITY HOSPITAL 2

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

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

2

Background. Diabetic nephropathy accounts for more than 45% of end-stage renal disease in

Taiwan. However, incidence of chronic kidney disease (CKD) for type 2 diabetic (T2D) patients and risk factors contributing to CKD development in T2D has not been well studied. This study aimed at assessing CKD incidence and its attributable factors.

Methods. We recruited 512 T2D patients from a community hospital in Taipei from 2006 to 2014 DQG IROORZHG WKHP XS WKURXJK 'HFHPEHU &.' ZDV GH¿QHG DV HVWLPDWHG JOXPHUXODU ¿OWUDWLRQ rate (eGFR) < 60 ml/min/1.73 m2, and advanced CKD as eGFR < 45 ml/min/1.73 m2. The incidence of CKD was calculated by the corresponding events divided by person-years observed for those with H*)5 PO PLQ P2 in the initial recruitment. Cox proportional hazards models were used to identify risk factors contributing to development of CKD or advanced CKD in the follow-up period.

Results. The baseline characteristics of our study subjects were as follows: age: 61.9 ± 10.2 years, T2D duration: 7.5 ± 7.3 years, mean follow-up: 5.9 ± 2.4 years, BMI: 26.6 ± 11.6, HbA1c: 7.5 ± 2.1%, systolic blood pressure: 134.1 ± 10.1 mmHg, diastolic blood pressure: 74.4 ± 5.9 mmHg, LDL: 111.7 ± 17.0 mg/dL, HDL: 52.6 ± 17.2 mg/dL, and TG: 140.2 ± 69.5 mg/dL. There were 144 subjects who developed CKD and 31 subjects who developed advanced CKD. The incidence rate of CKD and advanced CKD was 55.6 and 10.2 per 1000 person-years, respectively. The multivariable Cox models VKRZHG WKH VLJQL¿FDQW ULVN IDFWRUV IRU &.' GHYHORSPHQW ZHUH DJH \HDUV +5 > &, 1.21-1.62] compared to those < 50 years) and triglyceride > 150 mg/dL (HR = 2.02 [95% CI: 1.37 @ FRPSDUHG WR WKRVH PJ G/ 2Q WKH RWKHU KDQG WKH VLJQL¿FDQW ULVN IDFWRUV IRU DGYDQFHG CKD development was HbA1c in 7-9% (HR = 8.85 [95% CI: 1.96-39.91] compared to those < 7%), HbA1c > 9% (HR = 14.16 [95% CI: 2.19-91.56] compared to those < 7%), and triglyceride > 150 mg/ dL (HR = 4.78 [95% CI: 2.05-11.12] compared to those < 150 mg/dL).

Conclusion. T2D patients were the high risk group to develop CKD. In addition to poor glycemic control, hypertriglyceridemia was found as an Independent risk factor causing CKD development in T2D patients.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-06

ASSOCIATION BETWEEN DRB1 AND AUTOIMMUNE THYROID DISEASES IN PATIENTS WITH TYPE 1 DIABETES 1,2,3,4,5

YJ LEE, 1,6CY HUANG, 1,6WH TING, 7,8FS LO, 1YT CHIANG, 1CI CHAN, 9CH LIN, 9 BW CHENG, 10WL WU, 11CM HUNG, 12HJ LI, 2CL LIN 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; 6Department of Nursing, MacKay Medicine, Nursing and Management College; 7Department of Pediatrics, Chang Gung Memorial Hospital; 8College of Medicine, Chang Gung University; 9Department of Pediatrics, Mackay Memorial Hospital HsinChu Branch; 10Department of Pediatric Endocrinology and Metabolism, Chuanghua Christian Children’s Hospital; 11Department of Pediatrics, Hsinchu Cathay General Hospital; 12Department of Pediatrics, St. Martin De Porres Hospital

Type 1 diabetes (T1D) is heterogeneous in form and number of autoantibodies. At diagnosis and during follow-up of T1D, additional autoimmune phenomena are frequently observed. In descending RUGHU RI IUHTXHQF\ WKH\ DUH +DVKLPRWR GLVHDVH *UDYHV GLVHDVH FHOLDF GLVHDVH YLWDPLQ % GH¿FLHQF\ and Addison disease. Autoimmune thyroid disease (AITD) including Hashimoto disease and Graves disease are usually preceded by appearance of antithyroid autoantibodies (anti-microsomal, anti-TPO, anti-thyroglobulin, or anti-TSH receptor antibodies). We screened thyroid function on a cohort of T1D patients annually and as indicated by clinical manifestations for AITD. HLA complex is associated with various autoimmune diseases. Therefore we genotyped the DRB1 gene on these patients to evaluate the genetic inclination for developing AITD in T1D patients.

Material and Methods

The subjects were 467 patients with T1D. T1D was diagnosed on the basis of clinical PDQLIHVWDWLRQV DQG ODERUDWRU\ HYLGHQFH 3DWLHQWV KDG D +E$ F OHYHO RI D IDVWLQJ SODVPD JOXFRVH OHYHO PPRO O PJ GO DW OHDVW WLPHV RU D UDQGRP JOXFRVH OHYHO PPRO O mg/dl) with diabetic symptoms, and at least one of autoantibodies to islet cell antigens, glutamic acid decarboxylasee (GAD) and Islet antigen-2 (IA-2) or c-peptide level < 0.7 mmol/l (2.1 ng/ml) at random or < 1.1 mmol/l (3.3 ng/ml) at the peak by a glucagon test. *UDYHV GLVHDVH ZDV GH¿QHG DV SUHVHQFH RI JRLWHU VXSSUHVVHG 76+ HOHYDWHG IUHH 7 DQG SRVLWLYH DQWL 76+ UHFHSWRU DQWLERG\ +DVKLPRWR GLVHDVH ZDV GH¿QHG DV SRVLWLYH DQWL PLFURVRPDO DQWLERG\ RU anti-TOP antibody) with/without anti-thyroglobulin antibody, elevated TSH levels, and decreased or QRUPDO IUHH 7 OHYHOV (XWK\URLG ZLWK SHUVLVWHQW WK\URLG DXWRLPPXQLW\ (X37$ ZDV GH¿QHG DV DQ\ anti-thyroid antibodies detected for 2 times or more and persisting till the last examination with a euthyroid status. Euthyroid T1D patients without any anti-thyroid antibodies were as controls.

Genotyping of DRB1

110

Abstract

We genotyped DRB1 using HLAssure SE DRB Locus SBT Kit (Texas BioGene Inc., Taipei, Taiwan) on an ABI 3730XL DNA Analyzers (Applied Biosystems, Foster City, CA) with uTYPE6.0 SBT software (Invitrogen).

Statistical analysis

Allele frequencies were determined by allele counting. Differences, ORs, and 95%CIs for the association of genotype, allele, and carrier between patients with AITD and EuPTA and controls were determined. The Bonferroni correction, Pc = 1 –(1-P)n, was used for multiple comparisons where Pc was the corrected P value, P the uncorrected value, and n the number of comparisons. In this study, n ZDV IRU HDFK DOOHOH $ 3F YDOXH RI OHVV WKDQ ZDV FRQVLGHUHG VWDWLVWLFDOO\ VLJQL¿FDQW Results

198 (90 male and 108 female) patients contracted AITD or EuPTA. Their mean (SD) age at diagnosis was 7.2 (3.9) (ranged 0.8-17.8) years. The current age 26.0 (6.8) (9.3-39.7) years. Controls were 269 (128 male and 141 female) patients. Their mean age at diagnosis was 8.5 (4.4) (ranged 1.019.0) years. The current age 22.3 (7.9) (5.9-44.4) years.

Alleles DRB1*03:01, *09:01, and *04:05 were major alleles. Allele DRB1 ZDV VLJQL¿FDQWO\ more frequent in patients with AITD or EuPTA than in controls, 121/396 (30.6%) vs 123/538 (22.9%).

The allele conferred a risk to AITD or EuPTA, OR (95%CI) = 1.48 (1.11-1.99), P = 0.008, Pc = 0.056.

Conclusion

T1D patients are prone to AITD or EuPTA. The inclination might be influenced by genetic factors. Allele DRB1*09:01 might confer a risk to AITD or EuPTA. Other genes in the HLA complex should be genotyped to further understand the mechanism.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-01

PROTEOMIC ANALYSIS OF ANAPLASTIC THYROID CANCER CELLDERIVED EXOSOME FOR TUMOR THERAPY VIA LOVASTATININDUCED DIFFERENTIATION AND VILDAGLIPTIN-INHIBITED DIPEPTIDYL PEPTIDASE-IV (DPP-IV) ACTIVITY 1

CHIH-YUAN WANG, 2HAO-AI SHUI, 2TIEN-CHUN CHANG

1

Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University,Taipei, Taiwan; 2Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

Anaplastic or undifferentiated carcinoma cells proliferate rapidly and are easy to metastasize. Our UHVXOWV KDYH RYHUWXUQHG WKH QRWLRQ WKDW ORYDVWDWLQ LV EHQH¿FLDO WR FDQFHU WKHUDS\ DQG VXJJHVWHG WKDW the effect of Lovastatin on the undifferentiated thyroid carcinoma with the concentration of the dose is double-edged. In addition to Lovastation, inhibitors of Dipeptidyl peptidase-4 (DPP4, or CD26) may KDYH D VLJQL¿FDQW HIIHFW RQ FDQFHU ZLWK SULPDU\ HYLGHQFH IURP VHYHUDO UHSRUWV VXJJHVWLQJ WKDW '33 is involved in the proliferation and metastasis of prostate cancer cells and that DPP4 can promote or inhibit cancer cells by regulating their receptors, such as growth factors, chemokines, neuropeptides, and vasoactive peptides. In the study of prostate cancer also found that, DPP4 through the regulation of intracellular mitogenic peptide (mitogenic peptides) activity, thereby affecting the development of cancer. Vildagliptin is an inhibitor of DPP4 and belongs to the class of pancreatic islet enhancers.

It is a potent and selective inhibitor of DPP4 activity and has been shown to promote the growth of intestinal cancer cells. Whether the drugs affect the growth of undifferentiated thyroid cancer cells is still unclear. It is now known that cancer cells tend to increase the survival rate of cancer cells through the expression of heat shock proteins (HSPs) to protect against environmental stress and to treat cancer drugs, or to regulate the proliferation of cancer cells via the mTOR signaling pathway. As described in the previous studies, both Lovastatin and Vildagliptin have an effect on cancer cell development, but whether these two drugs through the HSP and mTOR for thyroid anaplastic carcinoma or thyroid follicular carcinoma of the tumor cells is still unclear. In addition, HSP is also one of the biomarkers of the exosome surface of cancer cells. In clinical applications, exosomal proteins are considered to have the potential to predict the diagnosis, treatment and biomarker of health and disease. , Exosomes have WKH UROH RI FHOO WR FHOO FRPPXQLFDWLRQ DQG VPDOO PROHFXOH WUDQVSRUW DQG FDQ LQÀXHQFH FHOO JURZWK After several tests, the results showed that ARO cells expressed DPP4 protein, and adding 1uM Vildagliptin and 25uM Lovastatin treatment of ARO cells and SW579 cells, found that Vildagliptin $52 FHOOV ZLOO PDNH WKH '33 SURWHLQ SHUIRUPDQFH GHFUHDVHG ,Q DGGLWLRQ WR FRQ¿UPLQJ WKDW $52 FHOOV GLG LQGHHG H[SUHVV '33 SURWHLQ LW ZDV DOVR FRQ¿UPHG WKDW 9LOGDJOLSWLQ GLG LQKLELW '33 SURWHLQ expression.

112

Abstract

OE-02

THE CLINICAL SIGNIFICANCE OF OXIDATIVE MARKERS IN WELLDIFFERENTIATED THYROID CANCER 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. Purpose: Age is a determinant factor for cancer staging and prognosis in well-differentiated

thyroid cancer (WDTC). Since reactive oxygen species are age and disease, especially cancerassociated, the expression of oxidative markers (OM) such as serum total antioxidant capacity (TAC); glutathione peroxidase (GPX); myeloperoxidase (MPO) and urinary 8-hydroxy-2-deoxyguanosine (8OHdG) were compared in healthy subjects and patients with benign or malignant thyroid tumors to H[SORUH WKHLU FOLQLFDO VLJQL¿FDQFH LQ WK\URLG GLVHDVHV Methods: Data were collected from 100 normal control (NC, 50 male and 50 female, aged 21.5 to 68.9 y/o) and 20 thyroid disease patients (5 male and 15 female, aged 28 to 67 y/o) during Sep 2013 to Aug 2014 from Chang-Gung memorial hospital. Among the thyroid disease group, OM were tested post-operatively in 15 WDTC (14 papillary and 1 follicular), pre-operatively in 1 follicular adenoma and 4 nodular goiter without operation (the five patients are classified as follicular neoplasm, FN).

Each of the OM was analyzed as impact factor on gender and age; the association of OM with thyroid function, thyroglobulin (Tg), and total radioiodine (I-131) dose was studied in WDTC. Kruskal-Wallis one-way ANOVA, Mann-Whitney U test and Pearson correlation were applied in this study with the p YDOXH OHVV WKDQ FRQVLGHUHG DV VWDWLVWLFDOO\ VLJQL¿FDQW Results: Among the OM, TAC and 8-OHdG were highly disease status-associated; TAC and 8-OHdG showed the lowest and the highest levels in FN, followed by WDTC and NC, respectively.

7$& *3; DQG 2+G* ZHUH JHQGHU VSHFL¿F ZKLOH 7$& ZDV VLJQL¿FDQWO\ KLJKHU *3; DQG 2+G* ZHUH VLJQL¿FDQWO\ ORZHU LQ PHQ *3; ZDV WKH RQO\ 20 KLJKO\ H[SUHVVHG LQ DOO VXEMHFWV DQG LQ :'7& aged above 45 (P < 0.05 in all subjects and P < 0.01 in WDTC). GPX was highly and moderately correlated with Tg and accumulated I-131 dose in WDTC (R = 0.822, P < 0.001; R = 0.577, P = 0.024, UHSHFWLYHO\ *3; ZDV DOVR VLJQL¿FDQWO\ KLJKHU LQ SDWLHQWV ZLWK GLVWDQW PHWDVWDVLV 3 1RQH RI the OM was correlated with TSH in WDTC regardless of metastasis or not.

Conclusion: We found that the structurally metastatic WDTC expressed significantly higher GPX, a selenium-containing enzyme, which was also significantly associated with serum Tg and accumulated I131 dosage. With these findings, GPX may be clinically available as a prognostic or even a diagnostic marker for advanced WDTC.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-03

URINARY IODINE ANALYSIS IN A THYROID CARCINOMA PATIENT REQUIRING RADIOIODINE THERAPY WITH PREVIOUS IODINATED CONTRAST AGENT USE 1

FAN-FEN WANG, 2CHUN-JEN CHANG, 3KAM-TSUN TANG, 3GING-SHING WON

1

Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan

Radioactive iodine (RAI) therapy is a beneficial, standard-of-care treatment for advanced differentiated thyroid cancer. Radioactive iodine uptake is increased by elevating thyrotropin (TSH) levels and initiating a low iodine diet (LID) prior to therapy. A pre-therapy spot urinary iodine concentration (UIC) of < 100 ug/L would support an adequate LID preparation. However, the use of iodinated contrast agents (ICA) is thought to interfere with the RAI therapy because of the enormous amount of iodine in these agents. We report a case of a post-thyroidectomy thyroid cancer patient requiring RAI therapy for pulmonary metastatic lesions but received ICA about 2 months prior to the scheduled radiation therapy.

Case report: This 75 year-old male was a patient of follicular thyroid carcinoma and had received total thyroidectomy. Before the thyroidectomy, computed tomography (CT) including ICA use had been performed as part of the work-ups to study the etiology of the multiple nodular lesions shown by plain chest X-ray study. At that time, aspiration cytology of the thyroid nodule had been FRQFOXGHG DV EHQLJQ QRQ VSHFL¿F FHOOXODU FKDQJH IRU WLPHV :HGJH UHVHFWLRQ RI RQH RI WKH SXOPRQDU\ lesions revealed follicular carcinoma of thyroid origin. After the thyroidectomy, he was on a LID in preparation for the RAI therapy.

The spot urine collected at the 45th, 46th, and 47th day (D45, D46, D47) after the CT scan were DQDO\]HG IRU WKH 8,& E\ WKH WKHUPDO F\FOHU GLJHVWLRQ PLFURSODWH PHWKRG 7KH UHDGLQJV DW ¿UVW UXQ ZHUH 47.6 ug/L, 614.5 ug/L, and 233.6 ug/L, respectively. Since the reading of D46 exceeded the calibration range of the assay, serial dilution was performed and yielded the result of 31.9 ug/L. In the assay without dilution, markedly decreased absorbance at 1 min after the Sandell-Kolthoff (S-K) reaction of D46 was found, and the condition was also found in D47. Serial dilution of D47 yielded the result of 51.5 ug/L. The patient received the scheduled RAI therapy under recombinant human TSH stimulation and the post therapy scan showed RAI uptake at the pulmonary metastatic lesions. Follow-up CT study at 5 months post RAI therapy showed decrease of the size of the pulmonary metastatic lesions. Serum thyroglobulin was 349 ng/ml (concomitant TSH 0.11 uIU/ml ; thyroxine suppression) before the RAI therapy and 118 ng/ml (TSH 0.97 uIU/ml; thyroxine suppression) at 4 months post therapy.

Conclusion: The current case demonstrated CT scan with ICA performed 2 months prior to RAI therapy didn’t inhibit RAI uptake. The unknown substance in urine interfering with the S-K reaction could be digested in diluted samples.

114

Abstract

OE-04

NEUROENDOCRINE TUMOR OF THE THYMUS ASSOCIATED WITH ECTOPIC ACTH SYNDROME: CLINICAL MANIFESTATIONS OF TWO CASE STUDIES 1

SHIH-CHEN TUNG, 2JUI LAN, 2JUI-CHU WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Department of Anatomic Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Introduction Thymic neuroendocrine tumors (NETs) are exceedingly rare tumors, accounting for approximately 0.4% of all carcinoid tumors and < 5% of all anterior mediastinal neoplasms. The prognosis of patients with NETs is poor because of the high incidence of local recurrences and distant metastases, even after a radical tumor resection. We report the clinical manifestations of thymic NETs in two patients with ectopic ACTH syndrome.

Case reports Case 1 A 53-year-oldman was admitted due to edema of face and bilateral lower limbs. Laboratory examinations showed baseline plasma cortisol > 60 ug/dL at 08:00, 24-h urinary free cortisol (UFC) > 480 ug/day, plasma ACTH 383 pg/mL, and plasma K 1.8 meq/L. Chest CT revealed bilateral lung nodules and chest wall masses, left anterior pleural tumor, left anterior mediastinal tumor, right T11 paravertebral mass, and diffuse mixed osteolytic and osteoblastic bony lesions. A pathological examination of bilateral chest wall biopsy showed neuroendocrine neoplasm of carcinoid tumor. An immunohistochemical (IHC) stain of the tumor revealed that it as positive for ACTH, chromograninA, synaptophysin, TTF-1, NSE, and Ki-67 in 3%. This is a carcinoid neuroendocrine tumor with ectopic ACTH syndrome and multiple organ metastases. The survival time from appearance of symptoms to death was 3 years and 5 months.

Case 2 $ \HDU ROG PDQ FRPSODLQHG ÀXVKLQJ IDFH DQG K\SHUWHQVLRQ IRU PRQWKV DQG ERG\ JDLQ NJ in the past 3 months. Laboratory tests showed that baseline plasma cortisol 110.6 ug/dL at 08:00 and 109.7 ug/L at 16:00, 24-h UFC 24310 ug/day, plasma ACTH 1480 pg/ml, and K level 2.2 meq/L. Sellar MRI did not reveal pituitary tumor. Chest CT demonstrated multiple small lung nodules, left anterior mediastinal nodule, mediastinal lymph nodes, left supraclavicular lymph node, precarinal lymph node, and right hilar mass encased pulmonary vessels. A pathological examination of resection of left lower lung, periarotic tumor, and mediastinal lymph nodes showed well-differentiated neuroendocrine carcinoma of the thymus with metastasis to lymph nodes. The results of IHC stain showed positive for ACTH, chromogranin A, synaptophysin, CD56 (N-CAM), AE1/AE3, Ki-67 1%, SSTR-2a, and SSTR115

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5. This is a case of thymic neuroendocrine carcinoma with ectopic ACTH syndrome and multiple metastases. The survival time from appearance of symptoms (2011/06) to death (2013/04) was 10 months.

Conclusion 1. Ectopic ACTH syndrome should be considered if an ACTH-dependent syndrome patient combines with hypokalemia.

2. Thymic NETs are rare and very aggressive tumors with poor prognosis due to high incidence of recurrence/metastasis after surgery.

3. Thymic NETs associated with Cushing’s syndrome (CS) have poorer outcomes than those without CS. 4. The treatment of choice of NETs is surgical resection of the tumors and the involved neighboring organs.

116

Abstract

OE-05

CASE SERIES OF THYROTOXICOSIS WITH LIVER FAILURE 1

AN-CHI LIN, 1HAO-CHANG HUNG, 1YE-FONG DU, 1CHING-HAN LIN, 1 HORNG-YIH OU 1

Department of Internal Medicine, Division of Endocrinology and Metabolism, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Objective Profound hepatic dysfunction in thyrotoxicosis is infrequently reported in the literature, and its PHFKDQLVP LV QRW ZHOO XQGHUVWRRG :H SHUIRUPHG D UHWURVSHFWLYH UHYLHZ RI ¿YH WK\URWR[LF SDWLHQWV complicated with liver failure who were admitted to NCKUH during 2011 to 2014.

Methods The clinical characteristics, thyroid function tests, causes of liver failure, and clinical courses of WKHVH ¿YH SDWLHQWV ZHUH FROOHFWHG DQG UHSRUWHG Results The range of the age was from 36 to 62 years old. Thyrotoxicosis-associated liver failure was QRWHG LQ DOO ¿YH SDWLHQWV DIWHU FRPSOHWH VXUYH\ WR H[FOXGH RWKHU FDXVHV RI OLYHU IDLOXUH :LWK GLIIHUHQW clinical scenarios, our patients received different treatment for thyrotoxicosis, and ended up with diverse outcomes. Three patients recovered completely with no sequalae. However, two patients died of complications of sepsis and multiple organ failure despite intensive medical care.

Conclusions Fulminant hepatic failure is a rare but serious complication of thyrotoxicosis. Jaundice in patients with thyrotoxicosis could be due to thyrotoxicosis itself, drug treatment for thyrotoxicosis, autoimmune hepatitis, or unrelated conditions like sepsis or viral hepatitis. Whether thionamides could be used in thyrotoxic patients with hepatitis and severe jaundice is inconclusive. The two fatal cases in our series were older in age, had multiple comorbidities, and complicated with sepsis and bacteremia.

We suggest these factors to be poor prognostic indicators in thyrotoxic patients complicated with liver failure.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-06

CHROMOGRANIN A AND SYNAPTOPHYSIN EXPRESSION IN AN ALDOSTERONE, CORTISOL CO-SECRETING ADRENAL INCIDENTALOMA 1

YU-CHUN HSUEH, 1HAN-WEN LIU, 1,2TING-I LEE, 1CHUN-JEN CHANG, 1 YU-MEI CHIEN, 1,3TING -WEI LEE, 1CHI FAN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2 Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ;3 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Introduction: Each adrenal glands are divided into two distinct parts, the cortex which originates from the mesoderm and the medulla that originates from the neural crest, ectoderm-origin. According to the cortex or medulla origin of an adrenal tumor, it can be separated into an adrenal-cortical tumor or pheochromocytoma, and the clinical manifestation differs as well. Here we present a patient with an adrenal incidentaloma co-secreting cortisol and aldosterone, with a positive chromogranin A and synaptophysin stains.

Case report: The patient was a 62-year-old woman with hypertension and chronic hepatitis C. She received abdominal CT scan for follow-up of her liver tumor. The liver tumor was later proved to be a benign OHVLRQ EXW DQ LQFLGHQWDO ¿QGLQJ RI D FP ORZ GHQVLW\ WXPRU DW OHIW DGUHQDO JODQG ZDV IRXQG LQ WKH abdominal CT. Chemical shift imaging of adrenal MRI showed signal drop in out-of-phase images.

Hormonal screening showed non-suppressible cortisol level on repeated 1-mg dexamethasone suppression test with low serum ACTH level. 24-hour urine free cortisol level, aldosterone-to-renin ratio, and 24-hour urine fractionated catecholamine level were negative. Adrenal incidentaloma with subclinical Cushing’s syndrome was diagnosed.

In the following years, patient had weight gain, diabetes mellitus, and non-traumatic compression fracture of T11 vertebra. Adrenal tumor size remained the same, but the aldosteroneto-renin ratio became positive. Primary hyperaldosteronism was later confirmed by captopril test. Considering the comorbidities caused by cortisol excess, she underwent laparoscopic left adrenalectomy. The microscopic images showed a cortical adenoma without nesting or other features of pheochromocytoma. But the immunohistochemistry stain showed positive synaptophysin and chromogranin A, which is usually seen in pheochromocytoma or adrenocortical carcinoma.

Discussion: 118

Abstract

On literature review, there were few cases of histopathology-proven adrenal cortical carcinomas and adenomas posing as pheochromocytomas clinically. The other cases were corticomedullary mixed tumors with variable clinical symptoms, and cell features of both cortical and medullary components. In our case, the patient had benign cortical cells microscopically but with a positive FKURPRJUDQLQ $ VWDLQ 7KH SDWKRSK\VLRORJ\ RU FOLQLFDO VLJQL¿FDQFH RI WKLV UDUH ¿QGLQJ QHHGV IXUWKHU investigations.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-01

CASE SERIES OF INTERFERON INDUCED TYPE 1 DIABETES MELLITUS 1

YU-PING HUANG, 1YE-FONG DU, 1CHING-HAN LIN, 1HAO-CHANG HUNG, 1 HORNG-YIH OU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Objective Interferon-based treatment is currently used in a number of conditions, including chronic viral hepatitis, hematological malignancies, renal cell carcinoma, and melanoma. On the other hand, interferon (IFN) therapy can also trigger several autoimmune diseases such as type 1 diabetes mellitus (T1DM). However, this adverse effect has not gained much attention.

Here, we report on four cases of IFN-induced T1DM at our institution.

Methods We reviewed the clinical characteristics, anti-islet autoantibodies, and clinical course of four patients for whom T1DM developed shortly after IFN therapy since 2010.

Results Three of the patients were female and one of the patients was male. The range of the age at onset of T1DM was from 38 to 55 years old. Two of them had history of T2DM before IFN treatment, but none of them had history of autoimmune diseases or family history of T1DM. The time period from initiation of the IFN therapy for their chronic hepatitis C to the onset of T1DM was 3 to 5 months.

Three of them presented with diabetic ketoacidosis at diagnosis. They all had positive glutamic acid decarboxylase 65 antibodies (GAD-Ab), and the titers were extremely high in three of them. All the patients remain insulin-dependent for up to 5 years.

Conclusions Fasting blood glucose level and hemoglobin A1c should be monitored during and after IFN therapy. For high-risk subjects, GAD-Ab may be screened before and after the IFN therapy to detect anti-islet autoimmunity for preventing the life threatening events (such as diabetic ketoacidosis) associated with T1DM.

120

Abstract

PD-02

POST-GASTRIC BYPASS HYPOGLYCEMIA(PGBH): A CASE REPORT AND LITERATURE REVIEW 1

PO-TSANG CHEN, 1KAI-JEN TIEN, 1CHEWN-YI YANG, 1NAI-CHENG YEH, 1 SHANG-GYU LEE 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan Background. Bariatric surgery is an effective procedure on treatment of severe obesity with

comorbidities, including type 2 DM, hypertension, obstructive sleep apnea or dyslipidemia. However, adverse event can occur after procedure. Since 2005, post-gastric bypass hypoglycemia(PGBH), FDXVHG GXH WR K\SHULQVXOLQHPLD KDV EHHQ LGHQWL¿HG DV D UDUH FRPSOLFDWLRQ DIWHU VXUJHU\ Methods. We report a morbid obesity woman who had received bariatric surgery developed severe recurrent hypoglycemia and PGBH was suspected.

Results. The 36-year-old woman who has uncontrollable type 2 DM and morbid obesity (BMI 36.7 kg/m2) received bariatric surgery. After three months, she was admitted due to urinary tract infection. During admission, recurrent episodes of cold sweating, dizziness, weakness with low fingerstick blood glucose were found. Lab data confirmed low serum glucose with endogenous hyperinsulinemia. She received diet intervention and pharmacological treatment but in vain. As result, partial pancreatectomy was performed to alleviate her refractory hypoglycemia. The pathology reports showed focally scattered islet hyperplasia.

Conclusion. Post-gastric bypass hypoglycemia is a rare bariatric surgery complication as a result of pancreatic hyperplasia. Clinician should be aware of this rare situation and differentiate other causes of hypoglycemia carefully.

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PD-03

HBA1C CHANGE AND 24-HR GLUCOSE FLUCTUATION AFTER VILDAGLIPTIN PLUS METFORMIN (SPC) TREATMENT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED ON METFORMIN MONOTHERAPY: A PROSPECTIVE, OPEN-LABEL STUDY 1

SHIH-TE TU, 1JEN-FU KUO, 1SHI-DOU LIN, 2CHIEH-KO KU

1

Department of Internal Medicine,Division of Endocrinology and Metabolism,Chang-Hua Christian Hospital,Chang-Hua,Taiwan; 2Novartis Taiwan Background: Metformin is the most widely used oral anti-diabetes therapy in patients with type

2 diabetes mellitus (T2DM). However, metformin alone is not sufficient to maintain the glycemic JRDOV RYHU WLPH WKXV ZDUUDQWLQJ WKH QHHG IRU FRPELQDWLRQ WKHUDS\ $OWKRXJK WKH HI¿FDF\ DQG VDIHW\ RI vildagliptin and metformin combination has been demonstrated in several randomized clinical trials, OLPLWHG GDWD LV DYDLODEOH RQ JOXFRVH ÀXFWXDWLRQ *O\FHPLF YDULDELOLW\ KDV EHHQ DWWULEXWHG WR SOD\ D UROH LQ GLDEHWLF FRPSOLFDWLRQV ([SORULQJ JOXFRVH ÀXFWXDWLRQ DV D PHDVXUH RI HI¿FDF\ LV RI VFLHQWL¿F DQG clinical importance.

Objective: 7R DVVHVV WKH HI¿FDF\ DQG VDIHW\ RI YLOGDJOLSWLQ SOXV PHWIRUPLQ PJ WZLFH GDLO\ in patients with T2DM uncontrolled on metformin monotherapy.

Methods: This was a 24-week, prospective, interventional, single-arm, open-label study FRQGXFWHG LQ D VLQJOH FHQWHU LQ 7DLZDQ 3DWLHQWV DJHG \HDUV ZLWK 7 '0 JO\FDWHG KHPRJORELQ >+E$ F@ ZKR ZHUH RQ D VWDEOH GRVH RI PHWIRUPLQ PJ GD\ IRU DW OHDVW ZHHNV SULRU WR WKH ¿UVW YLVLW ZHUH HQUROOHG DQG SUHVFULEHG YLOGDJOLSWLQ PHWIRUPLQ FRPELQDWLRQ WKHUDS\ WZLFH GDLO\ 7KH PHWIRUPLQ GRVH ZDV PDLQWDLQHG VDPH WKURXJKRXW WKH VWXG\ SHULRG 3ULPDU\ HI¿FDF\ HQGSRLQW ZDV change in HbA1c from baseline to week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), postprandial plasma glucose (PPG), percentage of patients reaching the glycemic goal RI +E$ F DQG DW ZHHNV RI WUHDWPHQW UHVSHFWLYHO\ DQG RSWLRQDO PHDQ DPSOLWXGH RI glycemic excursion (MAGE). Adverse events (AEs), serious adverse events (SAEs) and hypoglycemic events (HEs) were monitored and recorded.

Results: Of 40 enrolled patients, 37 (92.5%) completed the study. Mean ± SD age was 53.9 ± 11.9 years, 76.9% were women, mean T2DM duration was 3.9 ± 3.6 years; 69.2% patients had body mass LQGH[ NJ P2. Mean HbA1c, FPG and PPG at baseline were 7.2 ± 0.6%, 143.2 ± 22.5 mg/dL and 182.6 ± 4 4.3 mg/dL, respectively. The mean change in HbA1c from baseline to 12 and 24 weeks was í S DQG í S UHVSHFWLYHO\ 0HDQ )3* UHGXFWLRQV IURP EDVHOLQH WR ZHHNV ZDV í PJ G/ 0HDQ FKDQJH LQ 33* IURP EDVHOLQH WR ZHHN ZDV

122

Abstract

í PJ G/ DQG SDWLHQWV UHDFKHG JO\FHPLF JRDOV RI +E$ F DQG UHVSHFWLYHO\ DIWHU ZHHNV 0HDQ FKDQJH LQ K 0$*( ZDV í PJ G/ IURP EDVHOLQH WR week 24. Of 40 patients in the safety population, 57 AEs occurred in 23 (57.5%) patients, most of which were mild (89.5%). One SAE was reported (moderate in severity) but was not drug related. No HEs were recorded.

Conclusions: Vildagliptin and metformin combination treatment improved not only hyperglycemia but also glycemic variability, was well tolerated and can be considered as a suitable treatment option in patients with T2DM from Taiwan who were inadequately controlled on metformin monotherapy.

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PD-04

THE RELATIONSHIPS BETWEEN GAMMA-GLUTAMYLTRANSFERASE AND INSULIN RESISTANCE, GLUCOSE EFFECTIVENESS, FIRSTAND SECOND-PHASE INSULIN SECRETION IN OLD SUBJECTS 1

TE-LIN HSIA, 2JIUNN-DIANN LIN, 3YEN-LIN CHEN, 2CHUNG-ZE WU, 1DEE PEI

1

Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.; 2Division of Endocrinology, Department of Internal Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 3Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.

The pathophysiology of type 2 diabetes is still a mystery. Till now, insulin resistance (IR), glucose effectiveness (GE), first- and second-phase insulin secretion (FPIS, SPIS, respectively) are JHQHUDOO\ FRQVLGHUHG WR FRQWULEXWH ,Q WKH VDPH WLPH EHLQJ DQ LQÀDPPDWRU\ PDUNHU VHUXP JDPPD glutamyltransferase (GGT) is at least found to be related to IR and insulin secretion. Since diabetes in mostly prevalent in the elderly, to understand the relationships between GGT and IR, GE, FPIS and SPIS would be important.

We randomly enrolled 5082 and 5851 normal men and women whose age were over 65 years old (included). IR, FPIS, SPIS and GE were calculated by the equations developed by our group. In short, by using demographic and components of metabolic syndrome, these parameters could be estimated.

Simple correlation was applied to evaluate the slopes between GGT and other factors. The slopes of the correlation lines were compared. Due to the different units, the slopes were all converted into percentage so that they can be compared.

IR, FPIS and SPIS were positively and GE was negatively correlated to GGT. By comparing their slopes, it could be noted that, from the highest to the lowest r values, GE was the most tightly related to GGT, followed by IR, SPIS and FPIS. ,Q FRQFOXVLRQ WKH OHYHO RI **7 ZDV VLJQL¿FDQWO\ UHODWHG WR WKH DOO IRXU FRQWULEXWRUV RI GLDEHWHV Among them, GE was the most important one and FPIS was the least. Inflammation might play a crucial role in the pathogenesis of diabetes in old Chinese.

124

Abstract

PD-05

A CASE REPORT OF ACUTE KIDNEY INJURY AFTER 8 WEEKS OF EMPAGLIFLOZIN USE IN AN UNCONTROLLED TYPE 2 DIABETES KUO-YANG LEE Division of Endocrinology and Metabolism, China Medical University Hospital, Taipei Branch, Taiwan Object 7R UHSRUW D FDVH UHSRUW RI DFXWH NLGQH\ LQMXU\ DIWHU ZHHNV RI HPSDJOLÀR]LQ XVH LQ DQ

uncontrolled type 2 diabetic patient.

Method: The 67 years old woman has underlying disease of type 2 diabetes mellitus and mixed hyperlipidemia since 2011. She was prescribed with metformin (500) 1# tid, glimepiride (2) 1# bid, OLQDJOLSWLQ TG H]HWLPLEH VLPYDVWDWLQ TG DQG IHQR¿EUDWH TG +RZHYHU KHU blood glucose was noted uncontrolled under oral antidiabetic drugs since this year. (HbA1C was LQ )HEUXDU\ LQ -XQH DQG LQ $XJXVW (PSDJOLÀR]LQ PJ ZDV SODQQHG WR VXEVWLWXWH linagliptin for better glycemic control.

Result: Her renal function was serum creatinine 0.6 mg/dl (eGFR 98 mL/min/1.73 m2. by MDRD) in March, 2013, Cre 0.9 (eGFR 62) in May, 2014, Cre 1.1 (eGFR 49) in August, 2015, Cre 1.32 (eGFR 40) in April, 2016 and Cre 1.04 (eGFR 53) in June, 2016. Oral antidiabetic drugs were change to DPDU\O 0 ELG DQG HPSDJOLÀR]LQ VLQFH $XJXVW nd, 2016. However, she experienced nausea, dizziness, general discomfort and visited our emergency department on September, 28th. No fever, abdominal pain, vomiting or diarrhea was associated. No diuretic, renin-angiotensin system blockade, non-steroidal anti-inflammatory drug or Chinese medicine was taken. Deteriorated renal function was noted (BUN 70 mg/dl, Cre 3.56 mg/dl, eGFR 13 mL/min/1.73 m2 ). She was treated with intravenous hydration and was referred to endocrine outpatient the next day. Anti-diabetic drugs were adjusted to linagliptin 1# qd and Novomix (70/30) 12 U bid ac. Four weeks later (Oct, 26th), her serum Cre returned to 1.2 mg/dl (eGFR 45) and HbA1C decreased to 6.8%.

Conclusion: Although recent data (EMPA-REG Renal) had shown that empagliflozin could prevent worsening diabetic nephropathy, acute renal injury may also occurred especially in elderly patients or patients with chronic kidney disease (e GFR < 60). This class of drug should be used with FDXWLRQ LQ VSHFL¿F FRQGLWLRQ ,QWHQVLYH DQG UHJXODU UHQDO IXQFWLRQ IROORZ XS LV QHFHVVDU\

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-06

DYNAMIC CHANGES OF INSULIN REQUIREMENT IN DIFFERENT MEAL TIMES IN PATIENTS WITH TYPE 1 DIABETES 1

CHUNG-CHIH SHEN, 1CHING-JUNG HSIEH

1

Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.

Purpose: to evaluate different insulin requirement in different meals’ time in patients with type 1 diabetes.

Method: This is a retrospective study. We enrolled 30 patients from our carbohydrate counting education records in ward of Endocrine& Metabolism between Jan. 2005 and Dec. 2015. They had been admitted to the ward and received carbohydrate counting education and insulin dose adjusting. The including criteria is: type 1 diabetes mellitus, receiving basal + bolus insulin injection, carbohydrate/insulin (C/I) ratio and insulin sensitivity factor (ISF) noted before discharge. The exclusion criteria is: type 2 diabetes mellitus, receiving premixed or self-mixed insulin.We recorded the C/I ratio in different meals’ time, ISF from education chart. We also recorded age, gender, duration RI W\SH GLDEHWHV ERG\ ZHLJKW +E$ F OLSLG SUR¿OH FUHDWLQLQH DQG XULQH DOEXPLQ UDWLR EHIRUH DQG after carbohydrate counting education 3, 6 and 12 months later.We will use T-Test to test the different C/I ratio in different meals. The changes of all parameters before and after carbohydrate counting education 3,6 and 12 months later will be tested using a paired t-test.

Results:The demographic characteristics of study subjects are presented in Table 1. Our data FRQ¿UPHG WKH GLIIHUHQFH RI FDUERK\GUDWHV WR LQVXOLQ EHWZHHQ EUHDNIDVW OXQFK DQG GLQQHU $FFRUGLQJ WR SDLUHG W WHVWV WKH YDOXHV RI FDUERK\GUDWHV WR LQVXOLQ DW EUHDNIDVW ZHUH VLJQL¿FDQWO\ GLIIHUHQW IURP carbohydrates-to-insulin at lunch and carbohydrates-to-insulin at dinner( at morning v.s. at lunch, p = DW PRUQLQJ Y V DW GLQQHU S 7KH GDWD RI +ED F ZDV LOOXVWUDWHG WKH WUHQG LQ ¿JXUH 7KH UHFRUG RI +ED F YDOXH DW PRQWKV DIWHU FDUERK\GUDWH FRXQWLQJ ZHUH VLJQL¿FDQWO\ GLIIHUHQW ZLWK baseline but there was no difference between baseline and after 12months(baseline v.s. after 3months, p = 0.02; baseline v.s. after 6months, p = 0.013; baseline v.s. after 9 months, p = 0.024; baseline v.s.

DIWHU PRQWKV S ,W ZDV QRWHG WKDW K\SRJO\FHPLD HSLVRGH DWWDFN GXULQJ WKH ¿UVW ZHHN SDWLHQWV &RQFOXVLRQ :H KDG FRQ¿UPHG WKH GLIIHUHQFH RI FDUERK\GUDWH WR LQVXOLQ UDWLR ZKLFK LV higher at morning. It allows for reduced total insulin doses at noon and night and was associated with somogyi effect. Patient’s sugar control was improved after carbohydrate counting methods according to reduced carbohydrate counting. Further research is required to determine if factor confound the usual estimates of carbohydrate to insulin ratios and need to be factored into advice on insulin dosing for those with type 1 DM.

126

Abstract

PD-07

TESTING FOR HBA1C, IN ADDITION TO OGTT, IN PATIENTS WITH NO HISTORY OF DIABETES MAY HELP TO IDENTIFY PATIENTS WITH EARLY Ǻ-CELL FUNCTION IMPAIRMENT 1

YU-HSUAN LI, 1WAYNE HUEY-HERNG SHEU, 1WEN-JANE LEE, 1I-TE LEE, 1SHIHYI LIN, 1WEN-LIENG LEE, 1KAE-WOEI LIANG, 1CHIA-PO FU, 1JUN-SING WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan OBJECTIVE

,W KDV EHHQ UHSRUWHG WKDW ȕ FHOO IXQFWLRQ VWDUWHG WR GHFOLQH ZLWK DQ LQFUHDVH LQ HLWKHU IDVWLQJ RU 2-h plasma glucose from low normal to diabetic range. We aimed to investigate whether testing for glycosylated hemoglobin (HbA1c), in addition to oral glucose tolerance test (OGTT), may help to LGHQWLI\ HDUO\ ȕ FHOO IXQFWLRQ LPSDLUPHQW LQ SDWLHQWV ZLWK QR KLVWRU\ RI GLDEHWHV RESEARCH DESIGN AND METHODS This was a cross-sectional study included 1044 patients with no history of diabetes who were previously admitted for coronary angiography (CAG). Two to four weeks after hospital discharge, 2*77 ZDV FRQGXFWHG DQG +E$ F ZDV PHDVXUHG +RPHRVWDWLF PRGHO DVVHVVPHQW +20$ ȕ ZDV calculated to assess their beta cell function.

RESULTS According to OGTT, there were 432 (41.4%) patients with normal glucose tolerance (NGT), 432 (40.5%) with pre-diabetes, and 189 (18.1%) with newly detected diabetes. In patients classified as 1*7 E\ 2*77 WKRVH ZLWK +E$ F KDG VLJQL¿FDQWO\ ORZHU +20$ ȕ FRPSDUHG WR WKRVH ZLWK +ED F 3 1R VLJQL¿FDQFH GLIIHUHQFH EHWZHHQ +20$ ȕ LQ SDWLHQWV ZLWK +ED F DQG +E$ F ,Q SDWLHQWV FODVVL¿HG DV SUH GLDEHWHV E\ 2*77 WKRVH ZLWK +E$ F KDG VLJQL¿FDQWO\ ORZHU +20$ ȕ FRPSDUHG WR WKRVH ZLWK +E$ F 3 :KHQ DOO SDWLHQWV ZHUH GLYLGHG E\ +ED F OHYHOV WKRVH ZLWK +E$ F DQG +E$ F KDG VLJQL¿FDQWO\ ORZHU +20$ ȕ FRPSDUHG WR WKRVH ZLWK +E$ F 3

CONCLUSIONS Testing for HbA1c may help to detect early beta cell dysfunction, even in those who had normal glucose tolerance according to OGTT

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-08

INDICATOR ANALYSIS FOR RESPONSIVENESS TO SODIUMGLUCOSE CO-TRANSPORTER-2 INHIBITORS (SGLT2I) IN TYPE 2 DIABETIC TAIWANESE 1

CHIUNGYA CHEN, 1SUZ-TAH CHEN

Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Taiwan, R.O.C. Background: As a new class of glucose-lowering drugs, sodium-glucose co-transporter 2

inhibitors (SGLT2i), such as Dapagliflozin (Dapa) and Empagliflozin (Empa) are effective for controlling hyperglycaemia. This study aimed to identify possible indicators between SGLT2i responders and non-responders.

Design and Methods: Sixty-three poor controlled Type 2 Diabetic (T2D) patients were enrolled for either Dapa or Empa treatment. The duration of SGLT2i usage ranged from 3 to 6 months. Dipeptidyl peptidase-4 inhibitors, if ever used, were ceased on switching to SGLT2i. Clinical characteristics and parameters were documented initially and every 3 months. The dosing of Dapa and Empa or other DQWLGLDEHWLF DJHQWV ZDV EDVHG RQ FOLQLFDO MXGJPHQW $ 6*/7 L UHVSRQGHU ZDV GH¿QHG DV D GLIIHUHQFH RI hemoglobin A1c (HbA1c) equal to or more than 0.8% decrement. Binary logistic regression analysis was used to compare the difference between responder and non-responder groups.

Results: 63 out of 93 patients received more than 3 months of SGLT2i treatment, 9 stopped initially and 5 non-responders discontinued SGLT2i 3 months later due to adverse effects. 22 out of 63 (34.92%) were responders. Demographically, pre-treatment HbA1c level was higher (10.8 [10.1; 12.5] vs. 9.1 [8.4; 10.4]%, P = 0.000); initial Cr was lower (0.67 [0.615; 0.9] vs. 0.87 [0.77; 1.12] mg/ dL, P = 0.015); and eGFR was higher (98 [85; 137] vs. 82.7 [64.0; 99.5] mL/min/1.73m2, P = 0.004) in responders than in non-responders. HbA1c was significantly better in responders than in nonresponders (-1.65 [-2.9; -1.3] vs. -0.1% [-0.4; 0.7], P = 0.000). Average of 1 Kg body weight loss was GRFXPHQWHG LQ ERWK JURXSV ZLWKRXW VLJQL¿FDQW GLIIHUHQFH )LQDOO\ GXUDWLRQ RI VWDWLQ XVH ZDV VKRUWHU in responders than in non-responders (4.91 vs. 39.59 months, P = 0.012). For individual SGLT2i, the responders have higher pretreatment HbA1c (11.1 [10.2; 11.9] vs. 9.0 [8.3; 9.9], P = 0.001), higher eGFR (115 [85; 139] vs. 84.2 [52.8; 100.8], P = 0.009), and better Ă HbA1c (-1.6 [-3.1; -1.3] vs. 0.3 [-0.4; 0.7], P = 0.000) in the Empa group; and higher pre-treatment HbA1c (10.6 [9.5; 12.6] vs. 9.1 [8.4; 10.7], P = 0.023) and better HbA1c (-1.7 [-2.4; -1.3] vs. -0.15 [-0.4; 0.33], P = 0.000) in the Dapa group as well.

Conclusion: Higher HbA1c and eGFR are 2 independent factors for SGLT2is responsiveness.

128

Abstract

PD-09

METABOLIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN A REGIONAL TEACHING HOSPITAL IN TAOYUAN CITY: A CROSS-SECTIONAL STUDY IN DIABETES SHARED CARE MODEL OUTPATIENTS LI JUI-HSIANG, LO SU-HUEY Tao-Yuan General Hospital

Objective: the objective of this survey was to assess patients’ achievement of ADA guideline UHFRPPHQGDWLRQ IRU JO\FDWHG KHPRJORELQ OLSLG SUR¿OH EORRG SUHVVXUH %0, DQG UHQDO IXQFWLRQ VWDWXV in T2D outpatient clinics.

Methods: This is a descriptive cross-sectional study with 3875 ambulatory T2DM patients recruited between January and September 2016 and who are being treated in in a regional teaching hospital in Taoyuan city . Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glycosylated hemoglobin (HbA1c), creatinine, lipid profile, and urinary analysis. Laboratory parameters and blood pressure were evaluated according to ADA guideline recommendations Result Of the 3875 patients, 51.5% were female and the mean age was 63.2 ± 13.1 years. The proportion of age less than thirty years old was only 1.4% but the proportion of old than sixty-four years old was 43.9%. The mean diabetic duration was 11.9 ± 8.6 years. The proportion of glycemic FRQWURO ZLWK +E$ F EORRG SUHVVXUH FRQWURO XQGHU PPKJ /'/ OHYHO PJ GO DQG Triglyceride < 150mg/dl was 40.6%,79.0%, 59.5% and 57.0% respectively. The diabetes with normal %0, SURSRUWLRQ ZDV 7KH SHUFHQWDJH RI H*)5 UDQJH ZDV

VWDJH DQG (65' 7KH XULQH SURWHLQ RI XULQDU\ DQDO\VLV ZDV 3DWLHQWV ZLWK UHDFKLQJ $%& JRDO ZDV RQO\ Conclusion: Among individuals with type2 diabetes, there was still poor attainment of ADA recommendation (A1C, BP and LDL). 65.5% type 2 diabetes patients was overweight or obesity.

Interventions are urgently needed in order to prevent long term diabetic complication and overweight or obesity.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-10

A RESEARCH OF S14 PROTEIN IN THE LIPOGENESIS AND METABOLIC DISORDERS 1

YEN-TING CHEN, 2FEN-YU TSENG, 2PING-HUEI TSENG, 3DER-SHENG HAN, 2 YU-CHIAO CHI, 1,2WEI-SHIUNG YANG 1

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 3 Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital Beihu Branch, Taipei, Taiwan 2

Objectives: Spot 14 (S14) is a protein involved in the regulation of fatty acid synthesis in lipid-

producing tissues, primarily in the liver, lactating mammary gland and adipose tissue. However, the exact role of S14 in adipose tissue has not been investigated. In this study, we planned to study the regulation and function in adipogenesis and metabolic disorders.

Methods: We utilized S14 knockdown (KD) 3T3-L1 as an in vitro cell model to observe adipocyte differentiation. Adipogenesis-related gene mRNA expressions were analyzed by real-time PCR. ,QÀDPPDWRU\ F\WRNLQHV DQG (5 VWUHVV LQGXFHUV ZHUH XVHG WR PLPLF REHVLW\ UHODWHG LQVXOLQ UHVLVWDQFH An immunoassay was set-up to measure serum S14 concentration in human subjects.

Results: S14 KD reduced 3T3-L1 adipocyte differentiation and lipid accumulation. Several FDUGLQDO WUDQVFULSWLRQ DFWLYDWRUV GXULQJ DGLSRJHQHVLV VXFK DV ./) & (%3Į DQG 33$5Ȗ ZHUH down-regulated during S14 KD. The mRNA expression level of S14 was related to insulin resistance and the serum S14 concentration was negatively associated with thyroid-stimulating hormone and triglyceride levels.

Conclusions: S14 might play a critical role in adipocyte differentiation and participated in the mechanism of endocrine and metabolic disorders.

130

Abstract

PD-11

THE RELATIONSHIP BETWEEN SERUM RNASE-L LEVEL AND METABOLIC SYNDROME: A CROSS-SECTIONAL STUDY 1

YI-TING WANG, 2PING-HUEI TSENG, 1, 3CHI-LING CHEN, 1, 4YU-CHIAO CHI, 4 FENG-YU TSENG, 1, 4, 5, 6WEI-SHIUNG YANG 1

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan; 2 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taiwan; 3 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan; 4 Division of Endocrinology & Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan; 5 Center for Obesity, Lifestyle and Metabolic Surgery, National Taiwan University Hospital, Taiwan; 6 Graduate Institute of Medical Genomics & Proteomics, College of Medicine, National Taiwan University, Taiwan

Objectives: Ribonuclease-L (RNase-L) was considered as a ubiquitous enzyme involved in various cellular functions, especial in innate immunity. Recently, it was reported to participate in adipogenesis and myogenesis in rodents. Here, we developed a method to measure serum levels of RNase-L and analyze the association of RNase-L with metabolic syndrome (MetS).

Methods: A total of 396 subjects were recruited from a health check-up program of National Taiwan University Hospital (NTUH). An in-house RNase-L immunoassay was developed, and the serum RNase-L levels of these subjects were then measured. The association of MetS-related factors with serum RNase-L levels was assessed. To investigate this relationship, independent t-test assay, multivariate linear regression analysis, and odds ratio estimation were applied.

Results: The mean level of serum RNase-L of the subjects with MetS were lower than those ZLWKRXW ȝJ PO YV ȝJ PO P = 0.016). It was observed that the subjects with central obesity, elevated blood pressure, or impaired fasting glucose (IFG) had lower serum RNase-L OHYHOV LQ FRPSDULVRQ WR WKRVH ZLWKRXW 'LDVWROLF EORRG SUHVVXUH ȕ P = 0.031) and highGHQVLW\ OLSRSURWHLQ FKROHVWHURO +'/ & ȕ P = 0.037) were related to serum RNase-L in multivariate linear regression analysis. It is associated with a reduced risk of MetS (OR, 0.84, 95% CI, 0.71-0.99, P = 0.036), central obesity (OR, 0.82, 95% CI, 0.71-0.94, P = 0.004), elevated blood pressure (OR, 0.86, 95% CI, 0.74-0.99, P = 0.049), or low HDL-C (OR, 0.85, 95% CI, 0.73-0.99, P =

ZLWK HYHU\ ȝJ PO LQFUHDVH LQ VHUXP 51DVH / OHYHOV 0RUHRYHU DJH LV LQYHUVHO\ UHODWHG WR WKH levels of RNase-L in various analyses.

Conclusions: The serum RNase-L levels were negatively associated with MetS, unfavorable metabolic profiles and age in these subjects from a health check-up program. The mechanism underlying the link between RNase-L and MetS warrants further investigation.

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PD-12

EXPRESSION AND PURIFICATION OF CNTA PROTEIN FROM MICROBIOTA 1,2

SHIH-TING TSENG, 3CHIA SHIN YANG, 3YEH CHEN

1

Department of Endocrinology and Metabolism, Kuang Tien General Hospital, Taiwan; 2 Department of Food and Nutrition, Providence University, Taiwan; 3 Department of Biotechnology, Hungkuang University, Taiwan;

L-carnitine supplements are used to increase L-carnitine levels in people whose natural level of L-carnitine is too low because they have a genetic disorder, are taking certain drugs that uses up the body’s L-carnitine.. Choline supplements are often taken as a form of ‘smart drug’ or nootropic, due to the role the neurotransmitter acetylcholine plays in various cognition systems within the brain.

Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine and Choline through a microbiota-dependent mechanism. Previous study demonstrated that microbial produced TMA from L-carnitine by Rieske-type protein oxygenase/ reductase, CntA and CntB, and from Choline by Choline radical enzyme, CutC and CutD. To decrease the risk of dietary L-carnitine and Choline, inhibiting the function of CntA, CntB, CutC or CutD can be an idea for consideration. Therefore, CntA, CntB, CutC and CutD protein structures could be a basis for searching the suitable inhibitors. Until now, the CntA, CntB and CutD do not have the similar structures established. In this study, we plan to construct the plasmids containg cntA gene DQG WKHQ WUDQVIHFW WR ( FROL $IWHU RYHUH[SUHVVHG LQ ( FROL DQG VXEVHTXHQW VHULDO SXUL¿FDWLRQ VWHSV WKH SXUL¿HG &QW$ LV FU\VWDOOL]HG WR GLIIUDFW E\ ; UD\ VRXUFHG IURP V\QFKURWURQ WKH LQKLELWRU GUXJ RU chemicals searching will be conducted using the bioinformatics’ software. The suitable inhibitor may be produced as a functional food with the dietary L-carnitine and Choline. It will help to decrease the risk of atherosclerosis.

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Abstract

PD-13

SEASONAL VARIATION OF HBA1C CAN BE INDEPENDENT OF THE ANNUAL CHANGES OF GLYCEMIC CONTROL IN EACH SEASON 1

PO-HSUN CHEN, 2SHEU-CHEN LIU, 3CHIA-LIN LEE

1

Department of Internal Medicine, Taichung Veterans General Hospital, Chiayi branch, Chiayi, Taiwan; Department of Nursing, Taichung Veterans General Hospital, Taichung, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

2

Introduction: ,W KDV EHHQ UHSRUWHG WKH VHDVRQDO YDULDWLRQ RI +E$ F ZDV VLJQL¿FDQWO\ FRUUHODWHG ZLWK DPELHQW temperature in different countries in northern hemisphere. Decreased physical activity and increased calorie intake, especially during cultural events, were proposed causes.

Objective: This retrospective study was designed to evaluate the relationship between annual HbA1c changes of each season and seasonal variation of glycemic control at different HbA1c levels.

Methods: Among the patients in Diabetic Shared Care Network in Taichung Veterans General Hospital from -DQXDU\ WR -XQH ZH LGHQWL¿HG DGXOW SDWLHQWV ZLWK W\SH GLDEHWHV PHOOLWXV 7 '0 ZKR KDG +E$ F DQG IDVWLQJ EORRG JOXFRVH RI FRQVHFXWLYH VHDVRQV 7KH DYHUDJH GDWD LQ WKH ¿UVW VHDVRQ ZHUH FRXQWHG DV WKH EDVHOLQH 7KH\ ZHUH FODVVL¿HG LQWR JURXSV GHWHUPLQHG E\ GLIIHUHQW EDVHOLQH +E$ F OHYHO a :H FODVVL¿HG 'HFHPEHU WR )HEUXDU\ DV ZLQWHU 0DUFK WR 0D\ DV spring, June to August as summer, and September to November as fall/autumn.

Results: A total of 2014 patients with T2DM in the Diabetic Shared Care Network were investigated +E$ F Q +E$ F Q +E$ F Q 7KH EDVHOLQH HbA1c (%) of each group was 6.4 ± 0.4, 7.7 ± 0.6, and 10.3 ± 1.1, respectively (p < 0.001). In each RI \HDUV +E$ F LQ ZLQWHU ZDV VLJQL¿FDQWO\ KLJKHU WKDQ VXPPHU LQ HDFK JURXS DOO p-values were <

,Q WKH ORZHVW +E$ F JURXS +E$ F LQ WKH UG \HDU < ZDV VLJQL¿FDQWO\ KLJKHU WKDQ WKH VW year (Y1) in each season (Y1 vs Y3: 6.5 ± 0.7 vs 6.9 ± 0.9 in spring, 6.5 ± 0.7 vs 6.7 ± 0.8 in summer, 6.6 ± 0.8 vs 6.8 ± 0.8 in fall, 6.7 ± 0.7 vs 6.8 ± 0.9, repectively, all p-values were < 0.001). The opposed changes were found in the other two groups. In the middle-HbA1c group, the annual changes of HbA1c in each season (Y1 vs Y3) were 7.7 ± 0.9 vs 7.6 ± 1.1 in spring, 7.6 ± 0.9 vs 7.4 ± 1.0 in summer, 7.7 ± 1.0 vs 7.5 ± 1.1 in fall, 7.7 ± 1.0 vs 7.6 ± 1.1 in winter, respectively (all p-values were < 0.001). In the highest-HbA1c group, the annual changes of HbA1c in each season (Y1 vs Y3) were 9.6 ± 1.6 vs 8.6 ± 1.7 in spring, 9.2 ± 1.7 vs 8.3 ± 1.6 in summer, 9.1 ± 1.6 vs 8.5 ± 1.6 in fall, 9.3 ± 1.6 vs 8.5 ± 1.7 in winter, respectively (all p-values were < 0.001). The annual changes of fasting blood

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glucose in each season were not consistent with the HbA1c changes.

Conclusion: Clinical comprehensive diabetes care involving physicians, educators, nurses, and dietitians in real world could not improve the annual HbA1c in each season in the patients with good glycemic control despite seasonal variation of HbA1c still exhibited in all groups in 3 years. Previous proposed FDXVHV PD\ QRW HQRXJK H[SODLQ RXU ¿QGLQJV 2WKHU SK\VLRORJLF UHVSRQVHV WR WKH FKDQJHV RI DPELHQW temperature or sunlight exposure may be more important.

134

Abstract

PD-14

THE JOINTED EFFECT OF VASCULAR CELL ADHESION MOLECULE-1 AND CORONARY ARTERY DISEASE ON BRAINDERIVED NEUROTROPHIC FACTOR 1

I-TE LEE, 1JUN -SING WANG, 1CHIA-PO FU, 1WAYNE HUEY-HERNG SHEU

Division of Endocrinology and Metabolism, Taichung Veterans General Hospital Background: There is a high prevalence of depression in subjects with coronary artery disease

(CAD). Brain-derived neurotrophic factor (BDNF) is important for neural protection. In the present VWXG\ ZH H[DPLQHG WKH HIIHFWV RI LQÀDPPDWLRQ DQG &$' RQ %'1) Methods: Subjects who had undergone diagnostic angiography for angina were enrolled. Serum BDNF was determined at 0, 30 and 120min during an oral glucose tolerance test (OGTT) to calculate area under the curve (AUC) for BDNF. Serum vascular cell adhesion molecule-1 (VCAM-1) was GHWHUPLQHG DW IDVWLQJ &$' ZDV GLDJQRVHG EDVHG RQ KLVWRU\ DQG DQJLRJUDSKLF ¿QGLQJV Results: 6LJQL¿FDQWO\ ORZHU $8& RI %'1) YV QJ KU P/ 3 DQG higher serum VCAM-1 (583 ± 383 vs. 482 ± 171 ng/mL, P = 0.017) were noted in subjects with CAD than those without CAD. High VCAM-1 levels were an independent factor for low AUC of BDNF in subjects with and without CAD (95%CI between -0.011 and -0.002, P = 0.008; and 95%CI between -0.033 and -0.002, P = 0.029, respectively). Serum BDNF was lowest in the CAD subjects with high VCAM-1 levels at all time points during OGTT. Conclusion: Our results show that CAD was associated with low serum BDNF in response to OGTT, and VCAM-1 contributed a jointed effect with CAD on the BDNF.

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PD-15

ASSOCIATION BETWEEN SYSTOLIC BLOOD PRESSURE AND FUTURE RISK OF MORTALITY IN DIABETIC SUBJECTS AMONG U.S. ADULTS 1

CHING-YUN HU, 1YI-TING KUO, 2CHIA-LIN LEE

1

Taichung Veterans General Hospital, Wanciao Branch, 2Taichung Veterans General Hospital

Title: Association between systolic blood pressure and future risk of mortality in diabetic subjects among U.S. adults: NHANES 2001-2010 Background: Hypertension is a common comorbidity of type 2 diabetes. Epidemiological analyses show that hypertension is associated with increased cardiovascular(CV) event rates and mortality in individuals ZLWK GLDEHWHV 5DQGRPL]HG FOLQLFDO WULDOV KDYH GHPRQVWUDWHG WKH EHQH¿W RI ORZHULQJ blood pressure. However, optimal range of systolic blood pressure (SBP) in diabetes still remained controversial.

Object: The aim of this study was to examine the association between SBP and the risk of overall and CV mortality in subjects with diabetes.

Study design: This study was derived from National Health and Nutrition Examination Survey (NHANES) 2001-2010. Subjects less than 18 years old were excluded. Blood pressure and questionnaire of diabetes were recorded in NHANES enrollment. Diabetes was assigned if the subject reported a physician diagnosis of diabetes . The primary endpoint was all-cause mortality. CV mortality was GH¿QHG DV PRUWDOLW\ RI KHDUW RU FHUHEURYDVFXODU GLVHDVH $OO VXEMHFWV ZHUH IROORZHG XQWLO Result: Overall, 2744 subjects with diabetes were included. Among them, weighted percentage of male were 49.7%. The weighted average SBP was 130 + 0.5 mmHg. Over an average of 60 months of follow-up, the CV mortality rate was 4.8% and all- cause mortality was 17%. Comparing with the subjects of SBP 110-119 mmHg, the weighted risk of overall mortality were 1.96(1.02-3.78), 1.41 (0.79- 2.52), 1.40 (0.72- 2.70), 1.14 (0.54- 2.41), 3.01 (1.44- 6.30) and 1.88 (0.98- 3.58) for SBP of < 110mmHg, 120-129,130-139,140-149,150-159 and greater than 160, respectively.

Comparing with the subjects of SBP 110-119 mmHg, the weighted risk of CV mortality were 3.36(1.34- 8.38), 1.38 (0.46- 4.14), 2.04 (0.64- 6.54), 1.37 (0.35- 5.36), 4.75 (1.35- 16.72) and 3.71 (1.30- 10.60) for SBP of < 110mmHg, 120-129,130-139,140-149,150-159 and greater than 160, respectively.

Conclusion SBP below 110 mmHg was associated with higher risk of overall and CV related mortality in subjects with diabetes.

136

Abstract

PD-16

A CASE REPORT: USE OF GLP 1 AGONIST IN AN OBESE TYPE 2 DIABETES MELLITUS PATIENT WITH WEIGHT LOSS FAILURE AFTER VERTICAL BANDED GASTROPLASTY 1

HUAN-WEN CHEN, 1HSIAO-LIEN CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C

Introduction: Bariatric surgery (weight reduction surgery) includes a variety of procedures: reducing the size of the stomach with a gastric band; removing a portion of the stomach (sleeve gastrectomy); or resecting and re-routing the small intestines to a small stomach pouch (gastric E\SDVV VXUJHU\ $OWKRXJK EDULDWULF VXUJHU\ LV FRQVLGHUHG WR KDYH PRUH HI¿FDF\ WKDQ GUXJ WUHDWPHQW weight regain after bariatric surgery is a challenging problem. Glucagon-like peptide-1 agonists (GLP1 agonists) may be a resolute. We reported an obese type 2 diabetes case with weight loss failure after vertical banded gastroplasty. She received exenatide and then she had adequate blood glucose control and her body weight decreased gradually. We changed exenatide to liraglutide when her renal function GHFUHDVHG WR HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWH H*)5 P/ PLQ P2. After more 2 years, she still had adequate glucose control and her body weight maintained.

CASE REPORT: A 66-year-old female was obese since young adulthood. She was diagnosed with type 2 diabetes and hypertension at the age of 47. She initially received medication with oral antidiabetic drugs (OADs) and then had weight reduction surgery (vertical band gastroplasty, VBG) in the following year, September 1997. Her body weight decreased from 93 kg (BMI 40) in Sep 1997 to 70 kg (BMI 30.7) in Jun 1999. However, her body weight increased gradually to 113 kg (BMI 49.6) in April 2008. She tried some over-the-counter medication, which maintained her body weight at around 100~105 kg. Although she received OADs and basal insulin for many months, her blood glucose level was often more than 200 mg/dl. She received exenatide twice a day starting from May 2012. In August 2013, her body weight decreased to 86.7 kg (101.3 kg, BMI 44.4 before exenatide) and her HbA1C decreased to 6.4% (8.2% before exenatide). We tapered the dose of OADs and she still had adequate blood glucose control (A1C < 7%). We ever reported that exenatide is effective in controlling body weight and blood sugar level in an obese type 2 diabetes case with weight loss failure after vertical banded gastroplasty in the 35th annal meeting of the endocrine society and the diabetes association of the R.O.C (Taiwan) in March 2014. The patient’s renal function went downhill gradually. So we changed exenatide to liraglutide when her renal function decreased to eGFR < 50 mL/min/1.73m2.

After more 2 years and 5 months till Oct 2016, she still had good body weight (around 86 kg) and blood glucose control (A1C < ĸ炴 ).

After VBG, the patient lost about 23 kg in around 22 months. Unfortunately she regained her 137

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body weight after that, and she became heavier than before the weight reduction surgery. After receiving exenatide, her appetite decreased and her weight decreased gradually. Her blood glucose level was also under better control. We changed exenatide to liraglutide when her renal function went downhill. She did not regain her body weight and she still had blood glucose control. Although exenatide can not be used in impaired renal function, we can use liraglutide to keep the benefit of exenatide.

CONCLUSIONS: This case showed that GLP-1 agonist is effective in reducing body weight and improving diabetes control in an obese type 2 diabetes mellitus patient with weight loss failure after vertical banded gastroplasty.

138

Abstract

PD-17

PAINFUL DIABETIC POLYNEUROPATHY IS ASSOCIATED WITH 3-YEAR ALL-CAUSE MORTALITY IN T2DM 1

SHENG-SHU CHIANG, 2CHING-YUN HU, 3SHIH-YI LIN, 3HSIU-CHEN LIU, 3 JUN-SING WANG, 3I-TE LEE, 3YUH-MIN SONG, 3CHIA-PO FU, 3YI-TING TSAI, 3 WAYNE H-H SHEU, 3CHIA-LIN LEE 1

Divisions of Internal Medicine, Sinying Hospital, Tainan, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Wanqiao branch, Taichung Veterans General Hospital, Chiayi, Taiwan;3 Divisions of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan Introduction

Diabetic neuropathy is one of the most common complications in patients with T2DM. According to the previous study, there were increased mortality rate in those who had cardiovascular autonomic neuropathy. In addition, diabetic polyneuropathy was also an independent predictor of diabetes-related and all-cause mortality. However, there was no study reporting about the relationship between the cardiovascular risks or all cause mortality and the painful diabetic polyneuropathy (PDPN.) Our aim is to investigate whether there is increased risk of cardiovascular disease and all-cause mortality in PDPN in patients with T2DM. Method:

This retrospective study enrolled 2,877 outpatients with type 2 diabetes with completed survey of Douleur Neuropathique en 4 Questions (DN4) questionnaire from January 2013 to October 2013 in one RI PHGLFDO FHQWHU LQ FHQWUDO 7DLZDQ 3'31 ZDV GH¿QHG DV D WRWDO VFRUH H[FHHGLQJ SRLQWV 3DWLHQWV¶ characteristics and current medication list were also recorded. We reviewed the medical records and calculated about the CHA2DS2_VASc score (Congestive heart failure/left ventricular dysfunction, +\SHUWHQVLRQ $JH >GRXEOHG@ 'LDEHWHV 6WURNH >GRXEOHG@ ± 9DVFXODU GLVHDVH $JH ± DQG 6H[ category [female]) of each patient. One-way ANOVA was used to compare the CHA2DS2_VASc score among different DN4 scores. Cox proportional hazard model was used to estimate the impact of PDPN on future risk of overall mortality.

Results:

Overall, 226 (7.9%) patients were diagnosed as having PDPN, who were 109 (48.2%) men, mean 69.3 ± 12.8 years old, mean HbA1c 7.72 ± 1.63%, mean DM duration 13.1 ± 9.3 years, and insulin user 23%. Reviewing past history, there were 8% (non-PDPN, 3.4%) patients with PDPN had congestive heart failure (CHF), 15% (non-PDPN, 8.4%) had cerebrovascular accidents (CVA),

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and 9.7% (non-PDPN, 4.9%) had coronary artery disease (CAD). The higher DN4 total score was associated with higher CHA2DS2_VASc score (p for trend < 0.001.) After adjusting the association factors (HbA1c, age, sex, eGFR < 60, albuminuria, history of CHF, CVA, and CAD), three-year allcause mortality was increased in the patients with PDPN (HR = 1.862, p = 0.049.)

Conclusion:

PDPN may be a predictor of all-cause mortality in T2DM.

140

Abstract

PD-18

HYPOGLYCEMIA-RELATED EMERGENCY DEPARTMENT VISITS IN PATIENTS WITH TYPE 2 DIABETES: FOCUSING ON DPPIV INHIBITOR VS. SULFONYLUREA TREATMENT ON TOP OF METFORMIN 1,2

YING-JU CHEN, 2,3CHEN-CHANG YANG, 4MING-CHIA HSIEH, 5,6CHII-MIN HWU

1

Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Division of Clinical Toxicology & Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 5Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 6Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan Background: Add-on dipeptidyl peptidase-4 (DPP-IV) inhibitor treatment is an option for patients

with type 2 diabetes mellitus when metformin is not sufficient to achieve the desired therapeutic targets. However, real-world clinical data for this combination treatment are sparse.

Objective: The purpose of the study was to compare the occurrence of hypoglycemia-related emergency department (ED) visits associated with a combination therapy of DPP-IV inhibitor vs. sulfonylurea on top of metformin by using data extracted from The Taiwan National Health Insurance Research database (NHIRD).

Methods: We used a version of the Longitudinal Health Insurance Dataset of the NHIRD (with one million subjects sampled from all beneficiaries of the NHRID in 2010) for the current study.

All medical records of the selected insurers from 2000 to 2012, including outpatient, ED visits, hospitalization, medication use, and diagnostic data were obtained for the analysis. Patients with type 2 diabetes on dual oral combination antidiabetic therapy of metformin plus a DPP-IV (n = 5,319) vs. metfmormin plus a sulfonylurea (n = 13,601) were followed up. The primary outcome is the time to ¿UVW K\SRJO\FHPLD DVVRFLDWHG (' YLVLW RU WR WKH HQG RI VWXG\ :H XVHG WKH .DSODQ 0HLHU PHWKRG WR estimate the survival curves and the log-rank test to test the homogeneity between survival curves. +D]DUG UDWLR +5 DQG WKH FRQ¿GHQFH LQWHUYDO &, IRU WKH &R[ SURSRUWLRQDO KD]DUG PRGHO ZHUH used to evaluate the association between treatments of interests and primary outcome.

Results: Sulfonylureas were associated with higher risks for hypoglycemia-related ED visits (adjusted HR 9.45, 95% CI, 5.40 to 16.54) compared with DPP-IV inhibitors as add-on therapy to metformin. Other risk factors for hypoglycemia-related ED visits in this cohort included aging, female sex, and history of ischemic stroke.

Conclusion: 2XU GDWD VXJJHVWHG WKH EHQH¿WV RI '33 ,9 LQKLELWRUV DGG RQ WR PHWIRUPLQ WKHUDS\ concerning reduced risk for severe iatrogenic hypoglycemia compared with sulfonylureas.

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PD-19

OBESITY/OVERWEIGHT REDUCES THE RISK OF ACTIVE TUBERCULOSIS: A NATIONWIDE POPULATION-BASED COHORT STUDY IN TAIWAN 1,2

YUNG-FENG YEN, 3,4HSIAO-YUN HU, 5,6YA-LING LEE, 7PO-WEN KU, 2,8,9 DACHEN CHU, 2,10YUN-JU LAI 1

Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Education and Research, Taipei City Hospital, Taipei, Taiwan; 4Institute of Public Health and Community Medicine Research Center, National YangMing University, Taipei, Taiwan; 5Department of Dentistry, Taipei City Hospital, Taipei, Taiwan;6School of Dentistry, National Yang-Ming University, Taipei, Taiwan; 7Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan; 8Department of Neurosurgery, Taipei City Hospital, Taipei, Taiwan; 9Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 10Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan

BACKGROUND: In animal studies, obesity was associated with impaired T cell immune function. However, the effect of obesity on tuberculosis (TB) development has not been extensively studied. This nationwide population-based cohort study investigated the effect of obesity on TB GHYHORSPHQW LQ 7DLZDQHVH DGXOWV 0(7+2'6 :H LQFOXGHG DGXOW SDUWLFLSDQWV DJH \HDUV

from 3 rounds (2001, 2005, and 2009) of the Taiwan National Health Interview Survey. Obesity was GH¿QHG DV D ERG\ PDVV LQGH[ %0, NJ P2). Data on BMI and other covariates at baseline ZHUH FROOHFWHG E\ LQ SHUVRQ LQWHUYLHZV ,QFLGHQW FDVHV RI DFWLYH 7% ZHUH LGHQWL¿HG IURP WKH 1DWLRQDO Health Insurance database. Multivariate logistic regression was used to estimate the associations of obesity and overweight with active TB, with adjustment for age, sex, smoking, alcohol consumption, socioeconomic status, and other covariates.

RESULTS: In total, 241 new cases of active TB occurred during the study period. Obesity DGMXVWHG RGGV UDWLR >$25@ FRQ¿GHQW LQWHUYDO >&,@ DQG RYHUZHLJKW $25 95% CI, 0.49-0.91) were associated with lower risk of incident TB, after adjusting for demographic characteristics and comorbidities. There was a linear dose–response relation of BMI with active TB incidence (AOR per unit change in BMI, 0.92; 95% CI, 0.88-0.95; P < 0.001).

CONCLUSION: Obesity and overweight are associated with lower risk of active TB. Future studies should investigate the underlying mechanisms and clinical and epidemiological consequences RI WKHVH ¿QGLQJV

142

Abstract

PD-20

FACTORS ASSOCIATED WITH VISIT-TO-VISIT GLUCOSE VARIABILITY IN PATIENTS WITH TYPE 2 DIABETES 1

YU-WEI CHEN, 1JUN-SING WANG, 1WAYNE H-H SHEU, 1SHIH-YI LIN, 1I-TE LEE, 1 YUH-MIN SONG, 1CHIA-PO FU, 1CHIA-LIN LEE Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Introduction: Previous studies have demonstratedvisit-to-visit variability (VVV) of fasting plasma glucose (FPG) was associatedwithvascular events and mortality in patients with diabetes.We DLPHG WR HYDOXDWH ZKLFK IDFWRUV PD\DIIHFW )3* ÀXFWXDWLRQ LQ SDWLHQWV ZLWK W\SH GLDEHWHV Method:This retrospective cohort studyhad followed clinical data from7490 type 2 diabetes patients for one year. All of them had checked FPG at least once per season and coefficients of variance (CVs) of the patients’ FPG was calculated. The subjects were divided into two groups based on CVs of VVV of patients’ FPG. Baseline biochemical and demographicvariableswere measured and correlations of VVV with these clinical factors were investigated.

Result: The mean age and diabetes mellitus (DM) duration of the study population were66.7 years and 8.7 years, respectively, and the mean FPGand HbA1c levels of the patients were 148 mg/ dLand 7.6 %, respectively. Multivariate logistic regression analysis showed that CVs value was VLJQL¿FDQWO\ KLJKHU LQ SDWLHQWV WDNLQJ VXOIRQ\OXUHDV 68 25 S RU UHFHLYLQJ LQVXOLQ injection (OR = 3.33, p < 0.001),lower in those taking metformin (OR = 0.77, p = 0.002), and no FRUUHODWLRQZLWK RWKHU FODVVHVRI RUDO K\SRJO\FHPLF DJHQWV &9V YDOXH DOVR FRUUHODWHG VLJQL¿FDQWO\ ZLWK baseline FPG (OR = 1.06, p < 0.001), HbA1c levels(OR = 1.42, p < 0.001) and DM duration (OR = S EXW QHJDWLYHO\ ZLWK HVWLPDWHG JORPHUXODU ¿OWUDWLRQ UDWHOHYHOV 25 S

and it was not associated with age or gender.

Conclusion: 2XU ¿QGLQJV LQGLFDWHG WKDW 999 RI )3* ZDV KLJKHU LQ WKRVH UHFHLYLQJ PHGLFDWLRQV like SU or insulin, and in patients with longer DM duration or poorer glycemic control during the study period. VVV of FPG was lower in subjects with better renal function or under metformin treatment.

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PD-21

HYPERTRIGLYCERIDEMIA IS A RESIDUAL RISK FACTOR ASSOCIATED WITH NEW-ONSET DKD IN TYPE 2 DIABETIC PATIENTS WITHOUT HYPERTENSION 1

LI-LUN CHUANG, 1YU-HUNG CHANG, 1,2DER-WEI HWU, 1KUN-CHEN LIN, 1 YAU-JIUNN LEE 1

Lee’s Endocrinology Clinic, Pingtung 90000, Taiwan; 2Graduate institute of Clinical Medicine, Kaohsiung Medical University, Taiwan Background: Under standard care, risk factors for new-onset diabetes kidney disease (DKD) were

not yet clear, particularly in patients with type 2 diabetes mellitus (T2DM) without hypertension. The aim of this study is to reveal residual risk factors associated with new-onset DKD in T2DM patients without hypertension Material and Methods: Non-albuminuric normotensive T2DM patients with estimated GFR H*)5 PO PLQ P2 who had followed in the Taiwan Diabetes Shared Care Program were included. Physical and metabolic factors regarding the quality of diabetes control were recorded and calculated for their mean value. The development of DKD was defined as the new-onset of albuminuria or eGFR < 60 ml/min/1.73m2. Multivariate cox-regression analysis was used to identify the risk factors associated with new-onset DKD. Results: 563 T2DM patients with mean age of 58.4 were included. During the 4.8-year follow-up period mostly covered with statin therapy (72.8%), there were 67 patients (11.9%) recognized as the QHZ RQVHW '.' JURXS 7KHUH ZDV QR VLJQL¿FDQW GLIIHUHQFH LQ DJH JHQGHU VPRNLQJ VWDWXV GLDEHWHV disease duration, body mass index, mean HbA1C (non-DKD vs. DKD: 7.5 ± 1.1 vs. 7.6 ± 1.3%), mean total cholesterol (185.3 ± 18.1 vs. 186.2 ± 16.0 mg/dl), mean LDL-C (99.0 ± 15.1 vs. 100.4 ± 12.4 mg/dl) and mean diastolic pressure (74.1 ± 7.3 vs. 74.8 ± 7.5 mmHg) between the two groups. +RZHYHU WKH QHZ RQVHW '.' JURXS KDG D VLJQL¿FDQWO\ KLJKHU PHDQ YDOXH RI V\VWROLF SUHVVXUH ± 11.2 vs. 125.7 ± 12.0 mmHg; P = 0.036), triglycerides (130.2 ± 50.2 vs. 111.8 ± 44.0 mg/dl; P = 0.048) and lower mean HDL-C levels (54.5 ± 12.9 vs. 57.4 ± 10.6 mg/dl; P = 0.045). After multivariate FR[ UHJUHVVLRQ DQDO\VHV WKH UHVXOWV LQGLFDWHG WULJO\FHULGHV PJ GO LV WKH RQO\ UHVLGXDO PHWDEROLF risk factor associated with new-onset DKD with OR of 3.52 (95%C.I.: 1.48~8.34; P = 0.004).

Conclusion: In T2DM patients without hypertension under standard diabetes management, hypertriglyceridemia is an independent risk factor associated with new-onset DKD.

144

Abstract

PD-22

OPTIMIZING GLYCEMIC CONTROL IN TUBE-FED DIABETIC PATIENTS WITH CONTINUOUS GLUCOSE MONITORING 1

YE-FONG DU, 1HORNG-YIH OU, 1HAO-CHANG HUNG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Taiwan, R.O.C Background

Long-term care had become an important issue in recent years. Up to one-half of tube-fed elderly SDWLHQWV LQ ORQJ WHUP VHUYLFHV KDG GLDEHWHV PHOOLWXV +LJKO\ ÀXFWXDWHG JO\FHPLF RVFLOODWLRQ LV REVHUYHG in diabetic patients receiving bolus feeds 5~6 times a day, 3~4 hours apart. There was no consensus on how to improve the unintended hyperglycemia events and glycemic variability in long-term tube-fed patients with type 2 diabetes. Execution of basal bolus insulin injection as guideline suggested in this group of patients increase the care burden of the caregivers. Patient will need 5~6 times of injection a day if completely compliant to this regimen. An easier implemented regimen is more applicable for caregivers.

Method

Type 2 diabetic patients who were under enteral nutrition, aged 18-90 years old, followed at endocrinologist’s OPD in National Cheng Kung University Hospital were retrospectively reviewed if they had ever received CGM before and after regimen adjustment.

Enteral formula of these patients were evaluated by registered dietitian with re-designed food FRPSRVLWLRQ LQFOXGLQJ FDUERK\GUDWH DPRXQW SURSRUWLRQ DQG ¿EHU DPRXQW DV $'$ UHFRPPHQGDWLRQV before receiving CGM. Patients receiving bolus feeds were controlled with either metformin plus insulin glargine once-daily with or without DPP4 inhibitors or metformin/pioglitazone plus humulin N (NPH) and/or DPP4 inhibitors.

Patients receiving regimen adjustment had CGM exam at baseline and 3 months after implementation of new regimen when fasting blood glucose had been maintained below 130 mg/dl steadily. All glycemic variability was calculated using EasyGV© software Result

'XULQJ SHULRG IURP WR WKHUH DUH RQO\ SDWLHQWV IXO¿OOHG WKH HQUROOPHQW criteria. There were 2 patients received metformin plus NPH, 4 received metformin plus once daily insulin glargine with DPP4 inhibitors, 1 received pioglitazone plus DPP4 inhibitor and NPH, and 1 received metformin plus DPP4 inhibitors only. A participant self removed nasogastric tube before scheduled 3 months CGM follow-up (Case 8). For newly diagnosed diabetes patients on NG feeding (case 7) and patient with good response to SU (case 2), it is easier to control blood glucose within target range with metformin plus DPP4 inhibitors, with or without once daily long acting insulin.

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Metformin plus NPH twice daily and metformin plus insulin glargine plus DPP4 inhibitors both improved postprandial peak after bolus feeding with better quality of glycemic control.

Conclusion

Glycemic pattern in diabetic patients receiving bolus-feed were highly oscillated, especially at postprandial phase. Both regimen, metformin plus NPH bid injection or plus insulin glargine and DPP4 inhibitors offer altervative choice to improve quality of glycemic control in type 2 diabetic patients receiving bolus feeding.

146

Abstract

PD-23

LONG-TERM GLYCEMIC CONTROL AFTER 5 YEARS OF HEALTH EDUCATION ON GLYCEMIC CONTROL DURING HOLIDAY TIME IN TYPE 2 DIABETIC PATIENTS 1

FY CHEN, 1,2HS CHEN

1

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

2

OBJECTIVE— Our previous study demonstrated that type 2 diabetic patients receive holiday-

VSHFL¿F HGXFDWLRQDO SDPSKOHWV KDG EHWWHU JO\FHPLF FRQWURO GXULQJ WKLV &KLQHVH 1HZ <HDU¶V KROLGD\V than those received diabetic managed care. However, it is not well known whether the effects of regular, professional health education could improve long-term glycemic control during winter holidays.

RESEARCH DESIGN AND METHODS— Subjects were randomized to receive regular health education between Oct. 20 and Nov. 25 in 2004 and then every 3-4 months (program 1) or a special reminder pamphlets were given during the holidays (program 2). In this 5-year follow-up, we collected data from November 1st to the beginning of the Chinese New Year’s holiday as the pre-holiday period, and from the end of the holiday to April 30th as the post-holiday period.

RESULTS— A total of 110 subjects with type 2 DM were recruited for the study, and 89 patients were available for completing data (80%). The HbA1c levels before holiday was marginally statistically lower in the program 2 in the 5th year. The HbA1c levels after holiday was marginally statistically lower in the program 2 in the 1st, 2nd and 5th year. The mean HbA1c increased during holiday was marginally statistically lower in the program 2 in the 1st and 2nd year.

CONCLUSIONS—Our findings demonstrated that a special educational reminder pamphlet for the holidays led to improvements in glycemic control is non-inferiority to regular, professional health education during Chinese New Year’s holiday for 5 years.

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PD-24

ONE STOP SERVICE OF DIABETIC INTEGRATED CARE 1

CHUNGSEN CHEN, 1KUOMENG LIAO, 1PISUNG CHENG

Division of Endocrinology and Metabolism, Zhongxiao Branch, Taipei City Hospital

Introduction: Diabetes mellitus with poor glycemic control was notorious for its chronic complications. It ZDV GLI¿FXOW WR SHUVXDGH GLDEHWLF DJHG SHRSOH WR GLODWH SXSLOV IRU \HDUO\ UHWLQDO H[DPLQDWLRQ DQG RQ schedule to check other complications. Because of no survey of complications, no diagnosis, thus no managements were happened in the real world.

Methods: One visit in our clinics, we will provide survey of microvascular complications including of urine albumin excretion rate (nephropathy), non-mydriatic retinal camera (retinopathy), and quantitative sensory testing (neuropathy). Macrovascular complication (peripheral artery disease) was also assessed by ankle brachial index at the same visit. We served four complications survey in one stop.

We will check the rate of four examinations before and after the service. Satisfaction survey was also performed.

Results: The percentage of four examinations were increased after the service. Retinal examination rate increased from 67.6% to 72.8%, urine albumin excretion from 63.5% to 79.8%, quantitative sensory testing from 0% to 45%, and ankle brachial index from 89.9% to 95.1%. Satisfaction survey selected IRUP VXEMHFWV UHYHDOHG VDWLV¿HG 7KH QXPEHU RI OR\DO SDWLHQWV LQ RXU FOLQLFV ZDV DOVR increased from 4676 to 5147.Care quality including of Hba1c < 7 % rate was raised from 56.3% to 57.8%. LDL (low density lipoprotein) < 100 mg/dl from 59.5% to 61%.

Conclusions: One stop survey complications of diabetes were a patient-center service. Integrated care of patient could increase the percentage of diagnosed complications; thus, we could provide managements. One VWRS VHUYLFH QHHG VSDFH UHFRQVWUXFWLRQ DGGLWLRQDO VWDII DQG LQFUHDVHG LQVWUXPHQWV ,W ZDV D GLI¿FXOW road to walk. but it was a patient-center service. After the procedure reconstruction, we can see the EHQH¿W

148

Abstract

PD-25

GENETIC VARIANTS OF UROKINSE PLASMINOGEN ACTIVATOR IN SUBJECTS WITH TYPE 2 DIABETES MELLITUS AND DIABETIC NEPHROPATHY IN UREMIC STATE 1,2

CHUNG-ZE WU, 3JIN-SHUEN CHEN, 4LI-CHIEN CHANG, 5YUH-FENG LIN, 1,2 JIUNN-DIANN LIN, 1,2AN-TSE HSIEH, 6DEE PEI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C 3 Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C; 4 School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, R.O.C; 5 Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C; 6 School of Medicine, College of Medicine, Catholic Fu Jen University, Taiwan, R.O.C Background: The prevalence of type 2 diabetes mellitus (T2DM) rapidly boosts in recent decades

in worldwide. Diabetic nephropathy with uremia is one serious complications and leads to disability.

How to identify the patients with high risk of T2DM and diabetic nephropathy with uremia is an LPSRUWDQW LVVXH 8URNLQDVH SODVPLQRJHQ DFWLYDWRU X3$ FRQWULEXWHV WR ¿EULQRO\VLV LPPXQH UHJXODWLRQ cellular remodeling and repaired, and is associated with insulin secretion, islet cell regeneration, and atherosclerosis. The present study investigated the polymorphism of uPA in patients with T2DM, T2DM with fatty liver and T2DM in uremia. In addition, we also explored the uPA levels and activity in different genotype.

Material and Methods: There were 187 subjects enrolled. They were divided to health, T2DM, T2DM with fatty liver, and uremia groups. The uPA polymorphisms rs2227564 (C- > T), located on exon 6 and kringle domain of uPA, and rs2227568 (C- > T) located on exon 8 were explored.

Meanwhile, the uPA levels and activities in different genetic variants were measured.

Results: &RPSDUHG ZLWK KHDOWK DQG RWKHU JURXSV 7 '0 JURXS KDG VLJQL¿FDQWO\ KLJKHU IUHTXHQF\ of CC genotype on rs2227564. In other hand, uremia group had higher frequency CT genotype on rs2227568. Subjects carried with C allele of rs2227564 had significant lower uPA levels, but no significant difference on uPA activities. Subjects carried with T allele of rs2227568 had significant higher uPA levels, but lower uPA activities.

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PE-01

COCURRENT GRAVES’ DISEASE AND BILATERAL CAROTID ARTERY STENOSES (MOYAMOYA DISEASE): A CASE REPORT 1

SHIH-CHE HUA, 2PO-YEN YEH

1

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

Background: Moyamoya disease is a cerebrovascular disorder characterized by bilateral stenoses or occlusion of the terminal portions of the internal carotid arteries accompanied by typical netlike collateral vessels at the base of the brain. Although higher incidence in Asians, it is very rare to report patients suffering Moyamoya disease and Graves’ disease simultaneously. We present a young lady with the diagnosis of concurrent Moyamoya disease and Graves’ disease.

Case report: A 28-year-old lady with past history of Graves’ disease visited our hospital complaining of bilateral frontal headache followed by progressive weakness of his left arm, which had been getting worse for 3 days. An emergent head computed tomography showed one small acute infarction in the right parietal lobe; old infarction in the right frontal lobe, right corona radiata and left parietal lobe. /DERUDWRU\ GDWD VKRZHG ORZ 76+ ȝ,8 PO UHIHUHQFH DQG HOHYDWLRQ RI 7 reference: 84.6-201.8) and T4 (14.3 ng/ dl, reference: 4.6-12.0), abnormal AMIA: 1:6400(+). He was admitted to Neurology ward. A brain magnetic resonance imaging (MRI) scan showed acute infarct over right middle cerebral artery (MCA) territory. Computed tomography angiography (CTA) and magnetic resonance angiogram (MRA) all revealed bilateral carotid stenosis and the presence of collaterals. Laboratory screening tests for young stroke including protein C, protein S, and Rheumatologic exams all showed negative. As to treatment, antiplatelet therapy (Aspirin 300mg/day) and antithyroid therapy (methimazole 20mg/day combined with propranolol) were performed. After her neurological symptoms/signs improved, she was discharged and followed up at the clinic with the above mentioned drugs.

Discussions: Although it has previously been reported, coexistence of Moyamoya disease and Graves’ disease is very rare. Moyamoya disease and Graves’ disease are with implicated genetic factors because one gene locus of Moyamoya disease (chromosome 8q23, MYMY3) is very close to that of autoimmune thyroid disease (8q23-24). There has not been available for optimal treatment yet.

It has been suggested to use antiplatelet, antithyroid therapy, or revascularization surgery in some literatures.

150

Abstract

PE-02

ALTERNATIVE UPTAKE (FLIP-FLOP) OF METAIODOBENZYLGUANIDINE (MIBG) AND FLUORODEOXYGLUCOSE (FDG) IN DETECTING CATECHOLAMINE PRODUCING TUMOR: DEMONSTRATE 3 CASES 1

YU-PEI LIN, 2SHAUH-DER YEH, 3YEU-LIN LIU, 4CHING-HUEI KUNG, 5SEY-EN LIN, 6 CHEN-LING HUANG, 1,6CHUNG-HUEI HSU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 2 Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan 3 Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan; 4 Department of Radiology, Taipei Medical University Hospital, Taipei, Taiwan; 5 Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan; 6 Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan

Introduction: Radioiodine labeled MIBG (MetaiodoBenzylGuanidine) incorporated into noradrenalin storage granules is a functioning imaging for localizing and evaluating catecholamine producing tumors arising from adrenal gland or extraadrenal origin. We present three cases, malignant pheochromocytoma, paraganglioma and neuroblastoma, respectively, using

123

I-MIBG (MyoMIBG-I

123, FUJIFILM RI Pharma Co., LTD, Tokyo, Japan) scan for this rare disease.

Case1: \U ROG PDOH ZLWK LQWHUPLWWHQW WDFK\FDUGLD KRW ÀDVK RI IDFH K\SHUWHQVLRQ VXSUDQRUPDO urinary catecholamine levels and MRI showing a tumor in right adrenal gland received right adrenectomy for pheochromocytoma 12 years previously. Recurrence of the disease was suspected on account of reappearance of the symptoms. Urinary biochemical levels were normal. MRI revealed an irregular lesion at medial aspect of right suprarenal region. The lesion was MIBG avid. After surgery, metastatic paraspinal lymph node and invasion of surrounding soft tissue was proved. Recurrent PDOLJQDQW SKHRFKURPRF\WRPD ZDV ¿QDOO\ GLDJQRVHG 5HSHDW UHFXUUHQFH ZDV LGHQWL¿HG E\ 0,%* DQG MRI images recently, while FDG-PET was negative.

Case2: 60-yr-old male who had symptoms and markedly elevated urinary biochemical markers to suggest catecholamine producing tumor. CT scan revealed a huge retroperitoneal tumor in upper paraaortic region. The tumor appeared devoid of MIBG uptake (cold), while FDG-PET revealed intense uptake into the tumor. Paraganglioma was diagnosed after operation-pathological ¿QGLQJV Case 3: 24-yr-old male who harbored left adrenal gland neuroblastoma with lymph nodes metastases since 12 years of age (2003) had received operation, stem-cell transplantation and radio/ chemotherapy. Recurrence of the disease was noted in 2009, 2012, 2014 and 2015, respectively.

Recent CT scan showed soft tissue mass at left para-vertebral region of posterior lower mediastinum.

FDG-PET/CT revealed increased tumor glucose metabolism while MIBG scan showed faint 151

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visualization of the mass. Metastatic neuroblastoma involving soft tissue and lymph nodes was proven by surgery. The tumor tissue showed strong positive Anaplastic Lymphoma Kinase (ALK) protein expression.

Discussion:

123

I-MIBG whole body scan is a useful tool to detect and evaluate catecholamine

producing tumor. Concomitant utilization of FDG-PET can assess malignant potential of the disease. $OWHUQDWLYH XSWDNH ÀLS ÀRS SKHQRPHQRQ PD\ RFFXU EHWZHHQ 0,%* DQG )'* 3(7 LPDJLQJ

152

Abstract

PE-03

THE OCCULT ECTOPIC ACTH SYNDROME TREATED WITH METYRAPONE - A CASE REPORT 1

KAI-PI CHENG, 1HAO-CHANG HUNG, 1HORNG-YIH OU

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital

Endogenous Cushing’s syndrome is a disease with diverse manifestations due to prolonged exposure to excess glucocorticoids. It can be further divided into adrenocorticotropic hormone (ACTH) dependent and ACTH independent forms. Although the vast majority of patients with ACTH dependent Cushing’s syndrome are caused by the pituitary corticotroph adenoma, some are due to ectopic (extrapituitary) tumors that secrete ACTH. Around 6.7%-18.9% patients with ectopic ACTH V\QGURPH GHVSLWH H[WHQVLYH WHVWLQJ KDYH RFFXOW VRXUFHV RI $&7+ %HLQJ XQDEOH WR ¿QG RXW WKH RULJLQ RI $&7+ VHFUHWLRQ PDNHV LW GLI¿FXOW IRU WKH FOLQLFLDQV WR WUHDW WKLV NLQG RI SDWLHQWV +HUH ZH UHSRUW RQ a case with occult ectopic ACTH syndrome treated successfully with metyrapone.

A 62-year-old man was admitted to our hospital because of progressive limbs edema and unintentional body weight gain for one year. On examination, Cushingoid appearance including moon face, facial plethora, buffalo hump and central obesity was found. The am and pm cortisol OHYHOV ZHUH ERWK KLJKHU WKDQ ȝJ GO 7KH PLGQLJKW FRUWLVRO DQG $&7+ OHYHOV ZHUH ȝJ GO and 78.8 pg/ml, respectively. The cortisol levels were not suppressible by overnight and low dose dexamethasone suppression tests. In spite of more than 50 percent decrease of cortisol level under high dose dexamethasone suppression test, no pituitary gland lesion was detected by magnetic resonance imaging. In addition, there was hypokalemic metabolic alkalosis. Therefore, ectopic Cushing’s syndrome was impressed. However, chest, abdominal, and pelvic computed tomography did not UHYHDO DQ\ WXPRU $OWKRXJK ÀXRURGHR[\JOXFRVH )'* SRVLWURQ HPLVVLRQ WRPRJUDSK\ GLVFORVHG IRFDO FDG uptake in the ascending colon, biopsy through the colonoscopy showed colitis only. Moreover, other tests, including urinary 5-HIAA, 24 hours urinary catecholamines and VMA, serum calcitonin DQG &($ GLG QRW SURYLGH D FOXH WR ¿QG WKH FXOSULW 7R UHGXFH WKH KDUP RI FKURQLF H[SRVXUH WR H[FHVV glucocorticoids, after well discussing with the patient, we gave metyrapone to inhibit steroidogenesis.

The serum cortisol level decreased then. We will continue to evaluate the patient’s condition closely and provide necessary examinations to discover the occult source of ACTH secretion.

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PE-04

TUMORAL CALCINOSIS IN CHRONIC HEMODIALYSIS WITH HYPERPHOSPHATEMIA - A CASE REPORT YI-HSIN LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Taiwan Adventist Hospital

Tumoral calcinosis is an uncommon disorder in which calcium salt deposition is found in solitary or multiple, peri-articular soft tissue. The accumulations are often outside of the large joint capsule, such as hip, elbow, shoulder, ankle, and wrist. They cause progressive swelling around joints, but less pain and rare restriction of movement, secondary to compression of normal surrounding structures. They have potential to extrude and ulcerate the overlying skin. There are two types of tumoral calcinosis. The primary type is an inborn abnormality of phosphorus metabolism, known as hyperphosphatemic familial tumoral calcinosis, caused by increased renal absorption of phosphate due to loss-of-function mutations in the FGF23 or GALNT3 gene. (Less frequently normophosphatemia may also be noted). The secondary tumoral calcinosis is often associated with hyperphosphatemia in chronic renal failure with long term dialysis. We presented a 37-year-old female foreigner (Palau), end stage renal disease under hemodialysis since 2007, referred from international medical service for progressive, painful, and swelling over her right shoulder and scheduled percutaneous transluminal DQJLRSODVW\ IRU KHPRGLDO\VLV DUWHULRYHQRXV ¿VWXOD RI OHIW DUP

154

Abstract

PE-05

A CASE REPORT OF VON HIPPEL-LINDAU DISEASE 1

YU YI LIN, 2KUANG KUO WANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Cheng Hsin General Hospital, Taiwan, R.O.C Background. Von Hippel-Lindau disease (VHL) is a rare autosomal dominantly inherited

neoplastic syndrome and is characterized by highly vascular tumors of the retina, brain, and spinal cord, as well as benign and malignant tumors and/or cysts of the kidneys, adrenal medulla and sympathetic paraganglia, endolymphatic sac, epididymis, and broad ligament. VHL disease is caused by germ-line mutations of the VHL tumor suppressor gene, located on the short arm of chromosome 3 (3p25-26), regulating hypoxia-inducible factor ( HIF) for upregulation of vascular endothelial growth IDFWRU 9(*) SODWHOHW GULYHG JURZWK IDFWRU EHWD 3'*)ȕ WUDQVIRUPLQJ JURZWK IDFWRU DOSKD 7*)Į

and erythropoietin substances. Since the discovery of the VHL gene in 1993, genetic testing for VHL is widely available and will detect a disease-causing mutation in rate 95% to 100% of individuals who have a clinical diagnosis of VHL. Method. We report a case of VHL disease presenting with multiple pancreatic cysts, renal cysts and craniospinal hemangioblastomas.

Results. A 27-year-old female presented with poor glycemic control, intermittent nausea, vomiting and occipital headache for about 2 months. Physical examination revealed a thin girl with VRIW QHFN VWDEOH YLWDO VLJQV DQG RWKHUZLVH QR VLJQL¿FDQW DEQRUPDOLW\ 5RXWLQH DEGRPLQDO VRQRJUDSK\ revealed multiple cysts in the pancreas and two small cysts in the right kidney. To further identify the cause of those lesions, abdominal CT was performed. Because of worsening of headache combined with severe vomiting, brain CT was arranged to make sure whether there was intra-cranial lesion or not. Brain CT showed a cystic mass in left cerebellum, compressing fourth ventricle. Her symptoms persisted and aggrevated despite symptomatic treatments. Brain MRI with contrast also revealed a cystic mass in left cerebellum. Esophagogastroduodenoscopy revealed GERD, Grade A and external compression at antrum. Her family pedigree showed autosomanl dorminant heritage of multiple tumors involving pancreas, kidneys and retina. Taken together, she was clinically diagnosed as VHL disease. Left occipital craniotomy and removal of brain tumor under microscope was performed. The pathological report revealed a hemangioblastoma with extensive vascular network and neoplastic stromal cells; which is compatible with VHL disease. Twenty five days later, she was admitted again due to progressive low back pain with radiation to bilateral thighs.MRI of spine revealed intramedullary soft tissue mass located between T11 and 12. Laminectomy was performed and SDWKRORJLFDO UHSRUW FRQ¿UPHG WKH GLDJQRVLV RI KHPDQJLREODVWRPD )ROORZ XS 05, RI WKH EUDLQ DIWHU months of operation showed complete resolution of intracranial lesions.

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Conclusion. VHL disease is often difficult to diagnose due to the wide range of clinical

symptoms. Patients diagnosed with hemangioblastoma should be tested for VHL gene mutations. If mutations are present, the patient’s relatives should be offered a genetic consultation. VHL patients may develop further lesions many years after the initial diagnosis, despite complete excision of initial neoplasm. Continuous close and long-term follow-up in patients with VHL disease is necessary.

156

Abstract

PE-06

THE STRATEGY OF CUSHING’S DISEASE WITHOUT INITIAL MANIFESTATION OF PITUITARY ADENOMA IN MRI EXAMINATION: A CASE REPORT 1

WEI-FU HUANG, 1CHWEN-YI YANG, 1KAI-JEN TIEN, 1NAI-CHENG YEH, 1 SHANG-GYU LEE 1

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

The goal of our study was to the evaluate next step of Cushing’s disease with initial negative pituitary magnetic resonance imaging(MRI) Material and Methods

Cushing’s disease was diagnosed in a 30 year old female on the basis of clinical and biochemical ¿QGLQJV ZLWKRXW 05, OHVLRQV LQ WKH EHJLQQLQJ 7KH EORRG FRUWLVRO OHYHO ZDV HOHYDWHG WKH DYHUDJH OHYHO was 21.35ug/dl) with ACTH elevation (73.63 pg/ml) and it appeared no changeability of circadian rhythm.

Results

Due to the lack of indication for transsphenoidal surgery (TSS) with hesitating in inferior petrosal sinus sampling(IPSS) study, cabergoline monotherapy was prescribed. A 8-month course of treatment resulted in no amelioration of hypercortisolism. Re-arrangement of brain pituitary resonance imaging appeared a poorly-enhanced nodular lesion(7x5mm), favoring pituitary microadenoma. Transferred to neurosurgery for transsphednoidal surgery. Postoperatively the patient’s hypercortisolism and hyperprolactinaemia improved right away.

Conclusion

Pituitary ACTH tumor grows very slowly. The biochemical evidence usually preceded the LPDJLQJ ¿QGLQJV 6R WKH EHVW VWUDWHJ\ LQ RXU SDWLHQW ZDV QRW WR GR ,366 IRU FRQ¿UPDWLRQ RI &XVKLQJ¶V disease and closely following up with medication treatment. Besides, we extremely suggest repeating pituitary MRI examination at least 6 months later if hypercortisolism still existed.

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PE-07

CASE REPORT: A CASE OF UNCONTROLLED GRAVES’ DISEASE PRESENTING WITH MITRAL VALVE CHORDAE RUPTURE WITH SEVERE MITRAL REGURGITATION YU-LING LIN Feng yuan hospital, ministry of health and wealfare

Heart failure due to metabolic derangements is uncommon in clinical practice. Hyperthyroidism is associated with some serious complications involved the heart. When the precipitating factor is recognized and treatment is initiated in a timely fashion, These complications generally are reversible with appropriate treatment.

We report a 44 year-old female, a case of 1. arrthymia 2. hyperthyroidism lost F/U for yeart.

This time, she suffered from short of breath and DOE, with palpitation for 3 weeks. She came to CV OPD at 0713, PE revealed no obvious rales. EKG showed Af with RVR. X ray sowed bilateral pleural HIIXVLRQ DGPLVVLRQ LV VXJJHVWHG 6KH DGPLWWHG DW IRU VXVSHFW K\SHUWK\URLGLVP ÀDULQJ XS $IWHU admission, concor 1.25mg 1#BID with methimazole 2#TID were prescribed, ATD side effect education is done. Followed lab revealed TSH:0.02, free T4:4.66. We also arranged cardiac echo to follow cardiac function: mitral valve chordae rupture with severe MS were found(cardiac echo: Heart echo: RA/RV/LA enlarged. Af. LVEF 68%. Mod TR, peak systolic pressure gradient = 82mmHg, suggesting SXOPRQDU\ K\SHUWHQVLRQ 6HYHUH 05 GXH WR $0/ ÀDLO 0LOG $5 0LOG 35 7KXV ZH FRQVXOWHG &96 GRFWRU IRU IXUWKHU VXUJLFDO LQWHUYHQWLRQ 2S LQGLFDWLRQ ULVN DQG EHQL¿W ZHUH ZHOO H[SODLQHG WR WKH SW and family. Thyroid function must be controlled, and then surgery will be arranged as soon as possible.

After well preoperative preparation, MVR + tricuspid repair were performed on 1050929.

Postoperative course was smooth and warfarin was prescribed. She was discharged when INR reached the target level. Now postoperation course smooth, pt was under ATD therapy at meta opd.

Early recognition and prompt management of hyperthyroidism and associated cardiac complication can result in an imminent improvement of cardiac function.

158

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PE-08

THYROID STORM: CASE REPORT YU-LING LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Feng yuan hospital, ministry of health and wealfare

Thyroid storm is an endocrine emergency, remains a diagnostic and therapeutic challenge. The incidence of thyroid storm in the emergency department is low, with a mortality rate of 20%-30%; thus, it should not be overlooked. We present a 42 y/o female, a case of HBV carrier, denied thyroid disease in the past. In 105/08/15, she was sent to our ER due to shortness of breath, bilateral lower limbs pitting edema and decreased urine amount for several days. In our ER, acute pulmonary edema and cardiomegaly were noted, r/o CAD, she was admitted to ICU for intensive care. Under concerned of young age and without other vital organ dysfunction, we had checked thyroid function and primary hyperthyroidism(Free T4: 5, TSH: 0.02). Meta specialist was consulted and thyroid storm was impressed (Burch-wartofsky score: Temp:5 + CNS:0 + GI:20 + HR:20 + Heartfailure:15 + precipitant; 0 = 60). We added methimazole, lugol solution, hydrocortisone and propranolol for controlling. With monitoring her clinical performance, we kept shifting her medication dosage frequently. Diuretic agents was for fluid balance. With adjusting fluid suplement and medication dosage, we also tried weaning protocol. Her condition improved by closely monitored therapy guided by team consisting of Cardiologists and Endocrinologists. Endotracheal tube and ventilator were successfully weaning on 105/08/23. With relatively improving respiratory pattern, we transferred to ordinary ward for further care at 1050819. Now pt was under ATD therapy smoothly at meta opd.

Many cases of thyroid storm occur after a precipitating event. Early diagnosis and appropriate treatment may reduce mortality and morbidity rates. In the emergency departments, thyroid storm must be put on the list of differential diagnoses in 30-50 y/o patients, esp. female, if the patient is presenting with suspicious symptoms/signs.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-09

A CASE REPORT: THYROID VOLUME IN A PATIENT WITH HASIMOTO THYROIDITIS IS PROGRESSIVELY REDUCED AS A SEQUELA OF CHEMOTHERAPY FOR LYMPHOMA 1

HUAN-WEN CHEN, 2JIE-YU YOU, 3CHU-TEH CHEN, 1HSIAO-LIEN CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C; 2Division of Oncology and Hematology, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C; 3Division of Pathology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C

Hashimoto’s thyroiditis is a chronic lymphocytic thyroiditis, and it is an autoimmune disease. The thyroid gland is gradually destroyed. The thyroid may enlarge in early stage.

We report a 70 year-old female with large thyroid gland for years. Hypothyroidism was noted in Sep 2009. The level of Thyroid-stimulating hormone (TSH) was 22.6 uIU/ml. The level of Microsomal Ab (AMIA) was 1:100 (+). After eltroxin replacement, she was often under euthyroidism. But the thyroid volume was not reduced much. She ever received partial thyroidectomy to exclude thyroid lymphoma, but the pathology reported compatible with Hasimoto thyroiditis.

She sometimes had enlarged lymph nodes at neck. Diffuse large B-cell lymphoma was diagnosed after excision of lymph node at other hospital in May 2011. She received chemotherapty since that time. The thyroid volume was progressively reduced.

Hashimoto thyroiditis is a known risk factor for the development of primary thyroid lymphoma.

Chemotherapy can decrease the thyroid volume in primary thyroid lymphoma. But primary thyroid lymphoma was excluded after partial thyroidectomy in our patient. Our patient’s thyroid became atrophy after chemotherapy. So we suggested to check thyroid function and AMIA or anti-thyroid peroxidase antibody (anti-TPO ab) to exclude Hasimoto thyroiditis before the patient receiving chemotherapy for lymphoma. If the patient had Hasimoto thyroiditis, we suggested to check thyroid function frequently after the patient receiving chemotherapy for lymphoma. Adequate eltroxin replacement therapy is important when early detect thyroid atrophy and hypothyroidism.

160

Abstract

PE-10

PARATHYROID CARCINOMA MIMICKING ANAPLASTIC THYROID CARCINOMA 1

YIN-HUEI CHEN, 1CHING-CHUNG CHANG, 1CHING-CHU CHEN, 1YI-CHIH HUNG, 2 YEN-NIEN LIN, 1CHWEN-TZUEI CHANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical Universiry Hospital, Taichung, Taiwan, R.O.C.; 2Division of Cardiovascular medicine, Department of Internal Medicine, China Medical Universiry Hospital, Taichung, Taiwan, R.O.C.

Parathyroid carcinoma is very rare endocrine malignancy, it accounts for 0.5~5% all cases of primary hyperparathyroidism. We report a case of parathyroid carcinoma with brief literature review.

A 48-year-old previously healthy female presented with hypercalcemic crisis and PTH dependent hyperparathyroidism. Thyroid ultrasound revealed a 3.5x2.4x3.9 cm lobulated heterogenous K\SRHFKRLF PDVV LQ WKH OHIW ORZHU SROH RI WKH WK\URLG UHJLRQ 'LDJQRVWLF ¿QH QHHGOH DVSLUDWLRQ VKRZHG high tissue PTH level. Sestamibi scan displayed increased radionucleotide uptake in same left inferior thyroid. The patient underwent left thyroidectomy parathyroidectomy and left group VI lymph node dissection. Upon surgical exploration, the parathyroid mass was found to be grossly fibrotic and irregular in comparison to adjacent tissue. Histopathological examination revealed parathyroid carcinoma with contained capsular invasion while thyroid and lymph node specimens were negative for malignancy.

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PE-11

TRANSIENT THYROID SWELLING FOLLOWING FINE NEEDLE ASPIRATION: A RARE COMPLICATION OF THYROID FINE NEEDLE ASPIRATION 1

SHIH-CHANG LO, 1EDY KORNELIUS, 1CHIEN-NING HUANG, 1YI-SUN YANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital

We report a case of acute transient thyroid swelling following fine-needle aspiration, a rare complication and still unknown pathophysiology. A 43-year-old woman visited the clinic because of right thyroid goiter. The ultrasonographic pattern was an eccentric nodule with partial cyst and measured 24.3 x 18.2 x 14.2 mm. Fine needle aspiration of the right nodule was performed with a 19-gauge needle. Less than 5 minutes after the aspiration, the patient felt bilateral neck acute pain, especially during swallowing. Ultrasound showed rapid swelling of bilateral lobe: the right thyroid volume increased from 8.54 ml to 18.93 ml and left volume also increased from 7.06 ml to 14.84 ml. No evidence of bleeding on ultrasound and physical examination. The thyroid swelling returned to baseline after 3 days and painful sensation recovered about 1 week. Cytology was colloid, colloidophages, and scant follicular cells.

162

Abstract

PE-12

RARE ORGAN METASTASES IN A RARE SKIN NEUROENDOCRINE TUMOR 1

LO-CHIAO HUNG, 1MING-FONG TSAI, 1PEI-HUA HSU, 1YUIN-JU KUO, 1,2 CHIEN-CHIN HSU 1 2

Chiayi Chang Gung Memorial Hospital Kaohsiung Chang Gung Memorial Hospital

We described the case of a rare cutaneous neuroendocrine tumor with multiple organ involvement in a ninety-three years old woman who underwent right facial skin tumor excision biopsy. The immunohistochemical pathology report showed that the tumor cells were positively stained for CK-20, V\QDSWRSK\VLQ DQG FKURPRJUDQLQ $ DQG ZHUH QHJDWLYHO\ VWDLQHG IRU &. 7KH UHVXOWV FRQ¿UPHG WKH diagnosis of Merkel cell carcinoma (MCC).

F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was performed and showed multiple organ metastases, involving the thyroid glands, bilateral adrenal glands, small bowel, peritoneum, bone, and left subscapular soft tissue.

MCC is an uncommon neoplasm involving the skin, while very rare, subsequently metastasize to lymph nodes and other organs. These tumors are believed to arise from neuroendocrine-derived mechanoreceptor, Merkel cells, located at basal layer of the epidermis, that form synapse-like contacts with enlarged nerve terminals. The main risk factor is sunlight exposure, especially the ultraviolet light. The incidence of MCC has been rising steadily in Caucasian population, but few cases have been reported in Asian patients. We present here the 18F-FDG PET/CT images of a Merckel cell skin tumor manifested with rare multiple organ metastasis.

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PE-13

A CASE OF HYPOPITUITARISM PRESENTING WITH GALACTORRHEA 1

YIN-HUEI CHEN, 1CHING-CHU CHEN, 1CHING-CHUNG CHANG, 1YI-CHIH HUNG, 2 YEN-NIEN LIN, 1ZI-YUAN WANG Division of Cardiovascular medicine, Department of Internal Medicine, China Medical Universiry Hospital, Taichung, Taiwan, R.O.C.

Pituitary stalk interruption syndrome (PSIS) is a rare abnormality of the pituitary. It was first reported by Fujisawa et al in 1987. It is characterized by a classic triad of interrupted pituitary stalk on MRI, absent or ectopic posterior pituitary and anterior pituitary hypoplasia or aplasia. PSIS PDQLIHVWDWLRQV LQFOXGH D ZLGH VSHFWUXP RI FOLQLFDO SKHQRW\SHV DQG SLWXLWDU\ KRUPRQH GH¿FLHQFLHV RI variable degree and timing of onset. In addition, clinical presentation also varies according to age.

In adults, it presents as short stature and anterior pituitary deficiency. Perinatal events and genetic mutations may cause PSIS but the exact pathophysiology has not been illuminated yet. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Here in, we want to describe a 28 year old female with pituitary stalk interruption syndrome who presented with short body stature and galactorrhea.

164

Abstract

PE-14

A CROSS-SECTIONAL RETROSPECTIVE STUDY TO IDENTIFY INDICATORS FOR INITIATING THYROID HORMONE REPLACEMENT THERAPY IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM 1

PEI-CHI CHEN, 2CHIH-YUAN WANG

1

ུӏ֕Э྿ख‫܉‬ᚃଲུചхᗃऌȂ2 ѯτᚃଲϲऌഌхᗃϲϸ‫ݫ‬ऌ

Subclinical hypothyroidism (SCH) is defined by elevated serum thyroid stimulating hormone (TSH) levels and normal levels of total or free thyroxin. SCH is associated with increased risk of cardiovascular morbidity and mortality, but convenient risk indicators are lacking. We aimed to identify reliable indicators of cardiovascular risk for determining initiation of thyroid hormone replacement therapy in SCH patients. This is a cross-sectional retrospective study. Medical records of 412 consecutive healthy subjects with SCH who underwent routine health check-ups at National Taiwan University Hospital between January 1, 2009 and December 31, 2009 were reviewed.

Demographic, physical and clinical data were collected, including waist circumference, body mass index, thyroid function tests, fasting blood glucose, glycohemoglobin (HbA1c), and lipid profiles.

6XEMHFWV ZHUH GLYLGHG LQWR WKUHH JURXSV E\ +E$ F OHYHO DQG 1DWLRQDO Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) risk assessment was used WR HVWLPDWH FDUGLRYDVFXODU ULVN *URXS KDG VLJQL¿FDQWO\ KLJKHU IDVWLQJ EORRG JOXFRVH P < 0.001), postprandial glucose (P < 0.001), triglycerides (P < 0.001) and lower HDL-C (P = 0.039) than groups 1 and 2. HbA1c levels > 5.7% are associated with cardiovascular risk in SCH patients. HbA1c is an objective, convenient parameter for determining initiation of thyroid hormone replacement therapy in SCH patients with higher cardiovascular risk. Further studies are needed to demonstrate HbA1c capability for predicting cardiovascular risk in SCH patients and whether T4 treatment can improve outcomes.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-15

A CASE REPORT: ACUTE SUPPURATIVE THYROIDITIS WITH GAS FORMATION ORIGINATING FROM URINARY TRACT INFECTION 1

HUAN-WEN CHEN, 2YUAN-YUN TAM, 3I-HUNG SHAO, 1HSIAO-LIEN CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C; 2 Department of Otorhinolaryngology - Head and Neck Surgery, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C; 3 Division of Urology, Department of Surgery, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yi-Lan, Taiwan, R.O.C

Introduction: Because of a relatively high amount of iodine in the tissue, high vascularity and lymphatic drainage to the region, the thyroid is resistant to bacterial infection. So acute suppurative thyroiditis (AST) is rare. AST often involves the left lobe of the thyroid because it is often associated with the persistence of a pyriform sinus from the pharynx to the thyroid capsule. Therefore, AST is usually in children and young adults. It is often caused by oral bacteria including Staphylococcus aureus, Streptococcus hemolyticus, and pneumococcus. Other aerobic or anaerobic bacteria may also be involved. Acute emphysematous thyroiditis is AST with gas formation. It is a severe pyogenic infection of the thyroid gland characterized by the production of gas. It is a rarer type of AST. Case report: We present the clinical course of 78 year-old female patient with urosepsis and a large neck mass. She was a known diabetic for years on irregular oral hypoglycaemic agents. She was admitted to receive antibiotics for urinary tract infection (UTI) in early July 2015. One large F\VWLF JRLWHU DW ULJKW WK\URLG ZLWK WUDFKHDO FRPSUHVVLRQ ZDV FRQ¿UPHG E\ QHFN FRPSXWHG WRPRJUDSK\ (CT). But she refused further study or treatment for goiter. After completing the course of antibiotics, she was discharged. She fell down and she suffered from neck contusion about 4 days before this admission in late July 2015. She complained of more and more neck tightness. She was taken to the emergent room on July 27, 2015 when she had consciousness disturbance. On examination, she had WDFK\FDUGLD 7KHUH ZDV D ODUJH LOOGH¿QHG VZHOOLQJ LQ WKH ULJKW OREH RI WKH WK\URLG ZLWKRXW RYHUO\LQJ erythaema or edema. Pyuria, leukocytosis, and large neck mass were found. CT revealed a large mass, about 6.6x5.4x6.7 cm, with marked hetergeneous gas collection in right lobe of thyroid gland and the trachea was compressed on July 27, 2015. Subclinical hyperthyrodism was noted. She was diagnosed as having urosepsis and thyroid abscess, and hence she received emergency surgical exploration and ¿QH QHHGOH DVSLUDWLRQ -XO\ FF EURZQ WKLFN ÀXLG ZDV WDSSHG DQG WKH F\WRORJ\ UHSRUWHG abundant neutrophils and a few erythrocytes and a few histiocytes and few lymphocytes were seen.

Intraoperative neck sonography was done to screen out other focus of pus or hematoma. The patient was treated with antibiotic therapy followed by emergency surgical exploration and fine needle aspiration. Right lobe of thyroid became smaller initially, and then it enlarged again. Neck CT revealed a focal large air-trapping lesion in right lobe of thyroid gland with tracheal compression. So she

166

Abstract

UHFHLYHG VXUJLFDO H[SORUDWLRQ DQG GUDLQDJH RQ -XO\ 0XFK EORRG GDUN EURZQLVK ÀXLG DQG some pus were drained. Escherichia coli (E. coli) was the causative micro-organism cultured from the pus, urine and blood specimen. So we suspected that E. coli in the patient’s AST resulted from hematogenous spread. We changed antibiotics according to infection specialist’s suggestion. Her thyroid function became normal after 10 days. No antithyroid drug was prescribed.

Conclusion: AST is rare in old age people. Acute emphysematous thyroiditis is AST with gas formation. It is a rarer type of AST. Fine needle aspiration or surgical exploration and drainage to remove the pus is very important. We also need to search the infection source and give adequate antibiotics when the old age people suffer from AST.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-16

HYPERCALCEMIA FROM SUSPECTED MATASTATIC GASTROINTESTINAL STROMAL TUMOR (GIST) TO THE LUNG: A CASE REPORT 1

WEI CHE CHEN, 2CHEN WANG CHANG, 3PEI JAN CHEN, 1CHUN CYUAN LI

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospita, Taiwan, R.O.C.; 2Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospita, Taiwan, R.O.C.; 3Division of Chest Medicine, Department of Internal Medicine, Mackay Memorial Hospita, Taiwan, R.O.C.;

Hypercalcemia is a paraneplastic syndrome and is common in advanced lung cnacer, breast cancer and multiple myeloma. The invasion of bone from the malignancy could cause it. It also might be from the production of parathyroid hormone-related protein (PTHrP), parathyroid hormone or 1,25-dihydroxylvitamin D. Hypercalcemia of malignancy often means a poor prognosis.

We present a case report of hypercalcemia in a 84 years-old female. We found a lung tumor in the right apical lung from the computed tomography. Biopsy from broncoscopy was done and the pathological report present gastroinstetinal stromal tumor (GIST), most likely metastatic.

168

Abstract

PE-17

A CYCLIN-DEPENDENT KINASE INHIBITOR, DINACICLIB IN PRECLINICAL TREATMENT MODELS OF THYROID CANCER 1

SHU-FU LIN, 1JEN-DER LIN, 2CHUEN HSUEH, 3TING-CHAO CHOU, 4RICHARD WONG

1

Department of Internal Medicine, 2Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 3Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 4Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Background: We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK)

inhibitor, in the treatment of thyroid cancer.

Materials and methods: Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was DVVHVVHG XVLQJ :HVWHUQ EORW DQDO\VLV DQG LPPXQRÀXRUHVFHQFH PLFURVFRS\ &HOO F\FOH GLVWULEXWLRQ ZDV PHDVXUHG E\ ÀRZ F\WRPHWU\ DQG LPPXQRÀXRUHVFHQFH PLFURVFRS\ $SRSWRVLV DQG FDVSDVH DFWLYLW\ ZHUH PHDVXUHG E\ ÀRZ F\WRPHWU\ DQG ÀXRURPHWULF DVVD\ 0LFH EHDULQJ ÀDQN DQDSODVWLF WK\URLG FDQFHU (ATC) were treated with intraperitoneal injections of dinaciclib.

Results: Dinaciclib inhibited thyroid cancer cell proliferation in a dose-dependent manner.

'LQDFLFOLE KDG D ORZ PHGLDQ HIIHFW GRVH Q0 WR LQKLELW FHOO SUROLIHUDWLRQ LQ VHYHQ WK\URLG cancer cell lines. Dinaciclib decreased CDK1, cyclin B1, and Aurora A expression, induced cell cycle arrest in the G2/M phase, and induced accumulation of prophase mitotic cells. Dinaciclib decreased Mcl-1, Bcl-xL and survivin expression, activated caspase-3 and induced apoptosis. In vivo, the growth of ATC xenograft tumors was retarded in a dose-dependent fashion with daily dinaciclib treatment. +LJKHU GRVH GLQDFLFOLE PJ NJ FDXVHG VOLJKW EXW VLJQL¿FDQW ZHLJKW ORVV ZKLFK ZDV DEVHQW ZLWK lower-dose dinaciclib (40 mg/kg) treatment.

Conclusions: Dinaciclib inhibited thyroid cancer proliferation both in vitro and in vivo. These ¿QGLQJV VXSSRUW GLQDFLFOLE DV D SRWHQWLDO GUXJ IRU IXUWKHU VWXGLHV LQ FOLQLFDO WULDOV IRU WKH WUHDWPHQW RI patients with refractory thyroid cancer.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-18

RATHKE’S CLEFT CYST INDUCED PANHYPOPITUITARISM PRESENTED WITH RECURRENT HYPONATREMIA 1

CHIH-KANG WAN, 1CHUNG-MO CHANG, 2CHING-LING LIN

1

Department of Internal Medicine Cathay General Hospital Taipei; 2 Division of Endocrinology and Metabolism Cathay General Hospital Taipei

Case report: A 59-year-old Asian male complained of persistent dizziness, nausea and vomiting for one week, which prompted him to our ER. On arrival his vital sign showed BP:170/79 mmHg, PR:68/min, RR:20/ min. BT:37 ɗ . Lab data showed Hb:11.1, Na+ :113, K:3.8, Cr: 0.87, Osm: 235, CRP: 1.933, Urine Na: 113, Urine Osm: 436, FENa:2.3%. Brain CT showed no evidence of intracranial hemorrhage but widening of pituitary fossa was noted. Under the impression of hyponatremia and mild ileus, he was admitted for further evaluation. He denied fever, cough, rhinorrhea, chest tightness, dysuria, pitting edema, sore throat, palpitation, dyspnea, and tarry stool. He also denied decreased libido, LOBW and no loss of pubic or axillar hair. History review showed that hyponatremia had been found some 1.5 yr ago in another medical center while he suffered from the same S/S however no further evaluation had been conducted due to he recovered promptly. Diagnostic work-up for hyponatremia revealed TSH = 3.09, FT4 = 0.33, ACTH (8AM) = 14.9pg/ml, Cortisol (8AM) = 6.6, Testosterone = 2.0 ng/mL , GH = 0.05ng/ml, IGF-1 = 54.4ng/ml, LH = 0.40mIU/ml, FSH = 1.98mIU/ml, Prolactin = 20.2ng/ml with normal liver, cardiac and renal function. Panhypopituitism was impressed. An enhanced MRI of pituitary revealed a 1.4 x 1.6 x 1.3 cm sellar lesion with hyperintensity both on T1W and T2W images.

9LVXDO ¿HOG HYDOXDWLRQ E\ RSKWKDOPRJLVW VKRZHG QR YLVXDO ¿HOG GH¿FLW 1HXURVXUJHRQ ZDV FRQVXOWHG and the patient underwent endoscopic endonasal transsphenoidal hypophysectomy. Prior to surgery his hyponatremia responded poorly to 3% saline infusion but normalized promptly after replacement of WK\UR[LQ DQG FRUWLVRQH DFHWDWH EHIRUH VXUJHU\ +LVWRSDWKRORJLFDO ¿QGLQJV ZHUH FRQVLVWHQW ZLWK 5DWKNH¶V cleft cyst without evidence of malignancy. After surgery his serum sodium remained normal without further requirement of thyroxin and cortisone acetate therapy during OPD follow up.

Discussion: Rathke’s cleft cysts (RCC) are non-neoplastic remnants of Rathke’s pouch. They usually remain asymptomatic with a prevalence of 13% to 22% in autopsies series and treatment is rarely required.

However, symptoms could develop if adjacent structures are compressed. Presentation of symptomatic 5DWKNH¶V FOHIW F\VW FDQ EH QRQ VSHFL¿F ZKLFK LQFOXGH KHDGDFKHV YLVXDO GLVWXUEDQFHV DQG JDODFWRUUKHD Also hypopituitarism can be caused by compression of adjacent pituitary tissue or pituitary stalk. In VSLWH RI YDULDEOH UDGRSJUDSKLF IHDWXUHV RI 5DWKNH¶V FOHIW F\VWV KDG EHHQ UHSRUWHG WKHUH LV QR GH¿QLWH characteristic imaging finding to facilitate the diagnosis of Ratheke’s cleft cysts from other sellar 170

Abstract

lesions. Delayed diagnosis therafore is not uncommon in clinical setting. Surgery is not a routine solution for asymptomatic, incidentally found pituitary lesions but sometimes it is the only solution LQ V\PSWRPDWLF FDVH ERWK IRU GLDJQRVWLF DQG WKHUDSHXWLF SXUSRVHV 'H¿QLWH GLDJQRVLV RI V\PSWRPDWLF Rathke’s cleft cysts also require pathological evidence since the variable radiographic features of Rathke’s cleft cyst sometimes made it indistinguishable from other sellar lesions. Our case highlights WKH GLI¿FXOW\ RI GLDJQRVLQJ K\SRQDWUHPLD nd to panhypopituitarism and physicians should be vigilant in such clinical scenario to unearth the disease underneath which include Rathke’s cleft cyst.

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-19

HYPERALDOSTERONISM RELATED HYPOKALEMIA IN ANOREXIA NERVOSA, A CASE REPORT 1

CHIA-WEI LAI, 1HE-JIUN JIANG, 1WEI-WEN HUNG, 1SHYI-JANG SHIN, 1 PI-JUNG HSIAO Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital

$QRUH[LD QHUYRVD D SV\FKLDWULF HDWLQJ GLVRUGHU DOZD\V FRPSOLFDWHV ZLWK VLJQL¿FDQW VRFLDO DQG medical morbidities. The overall standard mortality rates were 6 folds in female and 5.0 folds in male patients with anorexia nervosa than in general population. Anorexia nervosa occurs in adolescents and adults worldwide. The estimated lifetime prevalence in adult is 0.6 ~ 4.2 % in Caucasian and it is reported to increase in a trend in Asia, including Taiwan.

Here, we reported a 37-year-old female admitted with main manifestation of general weakness, severe hypokalemia and emaciation. She looked extremely thin (BW 18 kg, BH: 162 cm, BMI < 7 kg/m2) and was bedridden for a long time. Her biochemistry demonstrated severe microcytic anemia, hyponatremia, hypokalemia and metabolic alkalosis. Secondary hyperaldosteronism was caused by her repeated, and long-time self-inducing vomiting and laxative misuse since she was 18 years old.

Extreme status of anorexia nervosa was diagnosed based on her BMI < 15 kg/m2, hypogonadotropic hypogonadism, hypercortisolism, non-thyroidal illness syndrome, severe osteoporosis (T-score of BMD -5) and multiple bony fractures. +HU OLIH WKUHDWHQLQJ PDOQRXULVKHG GLVRUGHU ZDV JUDGXDOO\ UHFRYHUHG E\ ÀXLG HOHFWURO\WHV VXSSO\ and total parenteral nutrition supplement. However, acute refeeding syndrome occurred with features of progressive short of breath, cardiomegaly and bilateral pleural effusion one week later. These symptoms were improved by intravenous infusion with albumin and loop diuretics. Then, she was discharged and sustained with home parenteral nutrition therapy. Her body weight was raised up to 30 kg in 6 months and was regularly followed at outpatient clinic until now.

All causes of the mortality rate among patients with anorexia nervosa were reported up to 5.9%.

Sudden cardiac death and suicide mainly account for 60% of the death. The exact mechanism of sudden cardiac death remains unknown but maybe relevant to left ventricular atrophy, myocardial fibrosis, alteration in cardiac conduction, high-grade atrioventricular block, QTc-prolongation in background of profound hypokalemia. Therefore, patients manifested with hypokalemia, metabolic alkalosis and extreme emaciation should be hospitalized and treated soon.

172

Abstract

PE-20

DEDUCED MECHANISM OF EPIMEDIUM INDUCED MYOTUBE HYPERTROPHY IN C2C12 CELLS 1

YI-AN LIN, 2MEI-CHICH HSU, 3SZU-TAH CHEN

1

National Taiwan Sport University, 2Kaohsiung Medical University, 3Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Linko BACKGROUD: Both insulin-like growth factor 1 (IGF-1) and androgen are known to be

associated with muscle hypertrophy through the activation of PI3K/Akt/mTOR signaling pathway; which is also important for myogenesis and therefore, attenuation of muscle atrophy. Recently, Epimedium and its constitutional flavonoids have been found to mediate PI3K/Akt/mTOR signaling cascades in myocytes and adipocytes; however, the mechanisms remain unclear.

PURPOSE: To study the difference between Epimedium and IGF-1 or androgen induced PI3K/Akt/ mTOR cascades.

METHODS: Epimedium extracts (EE) was applied to differentiated C2C12 myotubes in this study. +\SHUWURSK\ RI & & P\RWXEHV ZDV HYDOXDWHG E\ LPPXQRÀXRUHVFHQW VWDLQLQJ RI P\RVLQ KHDY\ FKDLQ (MyHC). The expression levels of IGF-1R, Akt, p70S6K, ERK 1/2, and MyHC proteins as well as MYH2, MYH4, MYH7, MRF4, myogenin, MAFbx, and MuRF1 mRNAs were assessed by western blot and RT-PCT, respectively.

RESULTS: EE enhanced C2C12 myotube hypertrophy through PI3K/Akt/mTOR activation and MyHC isoform overexpreession like IGF-1 and testosterone did. All these treatment alo promoted ERK 1/2 phosphorylation. Different from testosterone treatment, the activated ERK 1/2 induced by EE and IGF-1 could be abolished by LY294002 and rapamycin. Consequently, EE up-regulated MRF4 and MYH2 (MyHC 2A) gene expression could be reduced byPI3K/Akt/mTOR inhibition.

CONCLUSION: Our data suggested that EE stimulated myotube hypertrophy was more likely through IGF-1 related signaling pathways.

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PE-21

INFUNDIBULO-NEUROHYPOPHYSITIS WITH DIABETES INSIPIDUS: A CASE REPORT 1

TSE CHEN, 1PEI-CHI CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taiwan, R.O.C.

Backgournd. Hypophysitis is heterogenous in underlying etiologies and histopathological types. %HFDXVH RI WKH UDULW\ WKHUH LV VWLOO XQFHUWDLQW\ DERXW WKH FODVVL¿FDWLRQ QDWXUH FRXUVH DQG WUHDWPHQW RI hypophysitis. However, the incidence seemed to increase in these years.

Methods. We reported a case of infundibulo-neurohypohpysitis presenting as diabetes insipidus and review the literatures.

Results. A 51 y/o male who suffered from polydipsia, polyuria, and nocturia for three months.

It was noted that the patient had abnormally diluted urine and could be fully corrected with DDAVP. Central diabetes insipidus was diagnosed, and infundibulo-neurohypohpysitis was considered to be the cause after sella MRI. There was no compression symptoms and signs of pituitary. Considering of the risks of surgery, radiation therapy, or steroid use, the patient only received DDAVP replacement therapy. The pituitary image improved after a year, though, the deficiency of ADH seemed to be permanent.

Conclusions. Diabetes insipidus is a rare disease. The manifestations might be vague, and it was sometimes neglected at the first place. Therefore, we should keep this diagnosis in mind when the patients complain of polyuria and polydipsia.

174

Abstract

BP-01

RATIONALE, DESIGN FEATURES, AND BASELINE CHARACTERISTICS: THE HEART INSTITUTE OF JAPAN-PROPER LEVEL OF LIPID LOWERING WITH PITAVASTATIN AND EZETIMIBE IN ACUTE CORONARY SYNDROME (HIJ-PROPER) 1

ERISA KAWADA-WATANABE, 1HIROSHI OGAWA, 1RYO KOYANAGI, 1 HIROYUKI ARASHI, 1JUNICHI YAMAGUCHI, 2KUNIHIKO MATSUI, 1 NOBUHISA HAGIWARA 1

Department of Cardiology, The Heart Institute of Japan, Tokyo Women’s Medical University, Tokyo, Japan Department of General and Community Medicine, Kumamoto University Hospital, Kumamoto, Japan

2

BACKGROUND: In contrast to current guidelines in Western countries, moderate reduction of low-density lipoprotein cholesterol (LDL-C) is recommended for Japanese patients with atherosclerotic cardiovascular disease and dyslipidemia even in secondary prevention. HIJ-PROPER (Heart Institute of Japan-PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute coRonary syndrome) is a prospective, randomized, open-label, blinded endpoint multicenter trial designed to assess whether closely controlled LDL-C lowering with a standard statin dose plus ezetimibe, targeting LDL-C of < 70mg/dL, would reduce cardiovascular events more than standard statin monotherapy targeting LDL-C of < 100mg/dL as per the Japan Atherosclerotic Society guideline in patients with acute coronary syndrome (ACS) and dyslipidemia.

METHODS: We recruited patients with ACS and dyslipidemia who had undergone coronary angiography. Participants are randomly allocated to either intensive LDL-C lowering treatment (target LDL-C of < 70mg/dL; pitavastatin plus ezetimibe) or standard LDL-C lowering treatment (target LDL-C of 90-100mg/dL; pitavastatin monotherapy). The primary endpoint is a composite of total death, non-fatal myocardial infarction (MI), non-fatal stroke, unstable angina, and any ischemia-driven revascularization. Patients will be followed for a minimum of 3 years.

RESULTS: Between January 2010 and April 2013, 1734 patients were enrolled from 19 hospitals in Japan with a mean age of 65.6 years; 75.5% were men and 83.3% were statin-naïve. The qualifying $&6 ZDV DQ DFXWH 0, LQ 7KLV VWXG\ LV H[SHFWHG WR UHSRUW LWV ¿QGLQJV LQ $XJXVW CONCLUSION: HIJ-PROPER will determine whether targeting LDL-C of < 70mg/dL with pitavastatin plus ezetimibe can improve cardiovascular outcomes in Japanese patients with ACS and dyslipidemia in comparison to targeting LDL-C of 90-100mg/dL with standard pitavastatin monotherapy.

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BP-02

HAEMODYNAMIC EFFECTS OF COMBINATION THERAPY WITH THE DPP-4 INHIBITOR LINAGLIPTIN AND RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN PATIENTS WITH TYPE 2 DIABETES 1

M E COOPER, 2V PERKOVIC, 1,3P-H GROOP, 4B HOCHER, 5J CESCUTTI, 6 T MEINICKE, 6A KOITKA-WEBER, 7S THIEMANN, 7M EYNATTEN 1

Baker IDI Heart and Diabetes Institute, Melbourne, Australia 2George Institute for Global Health, Sydney, Australia 3Division of Nephrology, Department of Medicine, Helsinki, Finland 4Institute of Nutritional Science, University of Potsdam, Potsdam, Germany 5Boehringer Ingelheim, Reims, France 6Boehringer Ingelheim, Biberach, Germany 7Boehringer Ingelheim, Ingelheim, Germany

Background and aims: People with type 2 diabetes often require multi-drug therapy for adequate vascular risk factor management. Previous mechanistic clinical studies hypothesised an unfavourable potential drug-drug interaction between dipeptidyl peptidase (DPP)-4 inhibitors and angiotensin-converting enzyme inhibitors (ACEi) by postulating a clinically relevant increase in sympathetic activity and rise in blood pressure. We therefore investigated whether initiation of the DPP-4 inhibitor linagliptin on a background of renin-angiotensin system (RAS) blockade may alter clinical haemodynamic conditions.

Materials and methods: MARLINA–T2D™, a multicentre, double-blind, placebo-controlled clinical trial, randomised 360 patients with type 2 diabetes on a stable background of single RAS blockade (ACEi 33.3% [n = 120]; angiotensin receptor blocker [ARB] 66.7% [n = 240]) to either linagliptin (n = 182) or placebo (n = 178). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was considered as an exploratory safety endpoint and was conducted at baseline (BL) and after 24 weeks of treatment.

Results: In the treated set population, ABPM data were available for 298 patients (linagliptin, n = 155; placebo, n = 143) at baseline. Overall mean (SE) BL 24-h systolic blood pressure (SBP), diastolic BP (DBP), and pulse rate were 132.7 (0.7) mmHg, 75.9 (0.5) mmHg, and 77.3 (0.6) bpm, respectively.

At week 24, treatment with linagliptin was not associated with any clinically relevant haemodynamic changes: placebo-adjusted mean (SE) 24-h SBP, DBP, and pulse rate changes from BL were 0.0 (1.4) mmHg (95% CI –2.7, 2.7; NS), 0.0 (0.8) mmHg (95% CI –1.5, 1.5; NS), and 0.8 (0.7) bpm (95% CI –0.7, 2.2; NS), respectively. The presence of either ACEi or ARB background therapy at BL provided similar results (Table).

Conclusion: Adding linagliptin to stable RAS blockade background therapy was not associated with systemic haemodynamic changes. Our study supports its concomitant use for dual enzyme blockade of DPP-4 and ACE in patients with type 2 diabetes.

176

Abstract

BP-03

EFFECT OF EMPAGLIFLOZIN ON ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND HIGH CARDIOVASCULAR RISK 1

C WANNER, 2B ZINMAN, 3S E INZUCCHI, 4M MATTHEUS, 4A KOITKA-WEBER, 4 M EYNATTEN, 5H J L HEERSPINK, 6D CHERNEY. 1

Dept of Medicine, Würzburg Univ Clinic, Würzburg, Germany 2Lunenfeld-Tanenbaum Research Inst, Mount Sinai Hospital, Toronto, Canada 3Section of Endocrinology, Yale Univ, New Haven, CT 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 5Dept of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands 6Toronto General Hospital, Univ of Toronto, Canada.

Background: 6KRUW WHUP WUHDWPHQW ZLWK HPSDJOLÀR]LQ (03$ UHGXFHG DOEXPLQXULD LQ SDWLHQWV with type 2 diabetes (T2D). The present analysis aimed to explore short- and long-term effects of EMPA on albuminuria in EMPA-REG OUTCOME®.

Methods: Patients with T2D and established cardiovascular (CV) disease were randomized (1:1:1) to EMPA 10 mg, 25 mg or placebo in addition to standard of care. Changes in urinary albuminto-creatinine ratio (UACR, log-transformed) from baseline were analyzed for EMPA pooled vs placebo using a mixed model repeated measures analysis.

Results: 7020 patients were treated. At baseline, 59%, 29% and 11% had normo-, micro- and macroalbuminuria, respectively. At Week 12, placebo-corrected adjusted geometric mean ratio of UACR change from baseline with EMPA pooled was -7% (95%CI -12, -2; p = 0.0132), 25% (95%CI -31, -19; p < 0.0001) and -32% (95%CI -41, -23; p < 0.0001) in patients with normo-, micro- or macroalbuminuria at baseline, respectively. At Week 164, placebo-corrected adjusted geometric mean ratio of UACR change from baseline with EMPA pooled was -12% (95%CI -21, -4; p = 0.0072), -30% (95%CI -39, -19; p < 0.0001) and -32% (95%CI -47, -13; p = 0.0020) in these subgroups, respectively (Figure).

Conclusions: In patients with T2D and established CV disease, EMPA led to significant reductions in UACR from as early as Week 12, regardless of baseline albuminuria status. These results support both short- and long-term renal effects of EMPA on UACR.

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BP-04

RAPID ONSET OF RENAL EFFECTS WITH EMPAGLIFLOZIN IN TYPE 2 DIABETES: A CUMULATIVE RENAL EVENT ANALYSIS OVER TIME IN THE EMPA-REG OUTCOME® TRIAL 1

C WANNER, 2A KOITKA-WEBER, 2M MATTHEUS, 2M EYNATTEN, 3M E COOPER

1

Dept of Medicine, Würzburg Univ Clinic, Würzburg, Germany 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 3Baker IDI Heart and Diabetes Institute, Melbourne, Australia.

Background: Patients with diabetes are at high risk of developing chronic kidney disease &.' ,Q (03$ 5(* 287&20( HPSDJOLÀR]LQ (03$ VLJQL¿FDQWO\ VORZHG &.' SURJUHVVLRQ in patients with type 2 diabetes and established cardiovascular disease. To further explore the onset of the observed renal effects with EMPA we investigated hazard ratios (HRs) over time for the composite outcome of incident or worsening nephropathy.

Methods: Patients were randomized to receive EMPA 10mg, 25mg or placebo in addition to standard of care. The cumulative probabilities of experiencing incident or worsening nephropathy (i.e. progression to macroalbuminuria, doubling of serum creatinine accompanied by eGFR [MDRD] P/ PLQ P2, initiation of renal replacement therapy or death due to renal disease) were DQDO\]HG IRU SRROHG (03$ YV SODFHER LQ SDWLHQWV WUHDWHG ZLWK GRVH RI VWXG\ GUXJ +5V DQG CIs (obtained from Cox regression analyses) were derived at each time point following randomization until the last observation of the last patient. All events until the respective cut-off day were considered and patients without events were censored at that day.

Results: $ VLJQL¿FDQWO\ ORZHU ULVN IRU WKH FRPSRVLWH UHQDO RXWFRPH ZLWK (03$ YV SODFHER ZDV REVHUYHG ZLWKLQ WKH ¿UVW PRQWKV DQG WKLV HIIHFW ZDV PDLQWDLQHG WKURXJKRXW WKH WULDO )LJXUH +5V stabilized as the number of patients with events increased over time.

Conclusions: 5HQDO HIIHFWV RI (03$ RFFXUUHG ZLWKLQ WKH ¿UVW PRQWKV RI WUHDWPHQW 7KLV UDSLG RQVHW RI DFWLRQ PD\ UHÀHFW UHQDO KHPRG\QDPLF FKDQJHV DQG UHGXFWLRQ RI JORPHUXODU K\SHUWHQVLRQ

178

Abstract

BP-05

HEART FAILURE HOSPITALISATION OR CARDIOVASCULAR DEATH WITH EMPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES AND HIGH CARDIOVASCULAR RISK: ANALYSIS OVER TIME 1

D FITCHETT, 2J GEORGE, 2J LEE, 2H-J WOERLE

1

St Michael's Hospital, Division of Cardiology, University of Toronto, Toronto, Canada 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Background and aims: In the EMPA-REG OUTCOME trial, empagliflozin (EMPA) given in DGGLWLRQ WR VWDQGDUG RI FDUH VLJQL¿FDQWO\ UHGXFHG SRLQW PDMRU DGYHUVH FDUGLRYDVFXODU &9 HYHQWV (3-point MACE; composite of CV death, non-fatal myocardial infarction, non-fatal stroke) in patients with type 2 diabetes (T2DM) and high CV risk. This reduction was driven by a 38% reduction in CV death vs placebo (PBO). EMPA also reduced hospitalisation for heart failure by 35% and the composite of heart failure hospitalisation or CV death by 34%. We investigated hazard ratios with EMPA vs PBO for the composite of heart failure hospitalisation or CV death at time points following randomisation.

Materials and methods: Patients were randomised to receive EMPA 10 mg, EMPA 25 mg, or PBO in addition to standard of care. The cumulative probabilities of experiencing the composite of heart failure hospitalisation or CV death were analysed for pooled EMPA versus PBO in patients WUHDWHG ZLWK GRVH RI VWXG\ GUXJ LQFOXGLQJ DOO HYHQWV IURP UDQGRPLVDWLRQ XQWLO VWXG\ HQG +D]DUG ratios and 95% confidence intervals (obtained from Cox regression analyses) were derived at each time point following randomisation until the last observation of the last patient. All events until the respective day were considered and patients without events were censored at the respective day.

Results: Reductions in the risk of heart failure hospitalisation or CV death with EMPA vs PBO were observed by the first month and persisted for the duration of the trial (Figure). Hazard ratio stabilised as the number of patients with events increased over time.

Conclusion: In patients with T2DM and high CV risk, an early reduction in the risk of heart failure hospitalisation or CV death was observed in patients treated with EMPA. This reduction in risk persisted throughout the duration of the trial.

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BP-06

FACTORS ASSOCIATED WITH INSULIN ADHERANCE AMONG PATIENTS WITH TYPE 2 DIABETES: THE MOSAIC STUDY 1

THOMAS LEW (PRESENTER ONLY), 2MENGDONG HE, 3BRADLEY H. CURTIS, 3 JAY BAE, 3AYAD K. ALI, 4WILLIAM H. POLONSKY, 5LUCAS RISTA, 6 SALEM A. BESHYAH, 7MARTHA M. FUNNELL, 8RENAN MAGALHAES MONTENEGRO JR, 8VIRGINIA FERNANDES, 2SEOYOUNG C. KIM 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Brigham and Womens Hospital, Boston, MA, USA; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Diabetes Behavioral Institute, Del Mar, CA, USA; 5 University Rosario, Rosario, Argentina; 6Diabetes Clinic, Abu Dhabi, United Arab Emirates; 7University of Michigan, Ann Arbor, MI, USA; 8Universidade Federal do Ceará (UFC), Fortaleza-Ceara, Brazil

While insulin is the most effective glucose lowering therapy, adherence varies widely. Few studies KDYH LQYHVWLJDWHG WKLV LVVXH RYHU DQ H[WHQGHG SHULRG 7KLV DQDO\VLV LGHQWL¿HG IDFWRUV DVVRFLDWHG ZLWK insulin nonadherence within MOSAIc, a 2-year prospective cohort study. Patients with type 2 diabetes 7 ' \HDUV ROG DQG RQ LQVXOLQ IRU PRQWKV LQ FRXQWULHV ZHUH LQFOXGHG 'HPRJUDSKLF clinical, and self-reported data were collected at baseline and over 2 years. Insulin nonadherence was GH¿QHG DV PLVVLQJ DQ\ LQVXOLQ LQMHFWLRQV ZLWKLQ WKH SDVW GD\V RI D FOLQLF YLVLW 0XOWLYDULDEOH ORJLVWLF regression and multiple imputations were used in the analyses. Among 2706 patients, mean (standard deviation) age was 62.1 (10.8) years, 50% were female, and 608 (29.3%) were nonadherent at the end of study. These patients were younger (p < .0001), had lower diabetes knowledge test scores (p = .04), and were likely to be nonadherent at baseline (p < .0001), use mixed insulin (p = .0003), inject > 1 time per day (p = .001), have a worse experience with their insulin delivery system (p = .01), and have poor communication with their physicians compared to adherent patients. After adjustment, age and EDVHOLQH LQVXOLQ QRQDGKHUHQFH UHPDLQHG VLJQL¿FDQWO\ GLIIHUHQW EHWZHHQ WKH JURXSV ,Q FRQFOXVLRQ our study indicates that among patients with T2D utilizing insulin, younger patients with a history of poor adherence are less likely to be adherent over time.

Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at the American Diabetes Association – WK $QQXDO 6FLHQWL¿F 6HVVLRQV -XQH ± 1HZ 2UOHDQV /$ 86$

180

Abstract

BP-07

DEMOGRAPHIC AND CLINICAL FACTORS MAY PREDICT INSULIN PROGRESSION AND GLYCEMIC CONTROL AMONG PATIENTS WITH TYPE 2 DIABETES USING INSULIN: LEARNING FROM THE MOSAIC STUDY 1

THOMAS LEW (PRESENTER ONLY), 2AYAD K. ALI, 2BRADLEY H. CURTIS, 3 JAMES R. ROGERS, 3MENGDONG HE, 3ABDURRAHMAN ABDURROB, 4 BRUNO LINETZKY, 2JAY BAE, 2RAN DUAN, 5STEVE BAIN, 6MANOJ CHAWLA, 7 YOEL TOLEDANO, 8IKURO MATSUBA, 9MUSTAFA ARAZ, 10 WILLIAM H. POLONSKY, 3SEOYOUNG C. KIM 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA; 4Eli Lilly and Company, Buenos Aires, Argentina; 5Swansea University, Swansea, UK; 6Lina Diabetes Care Centre, Mumbai, India; 7Hillel Yaffe Medical Center, Maccabi, Petah Tikva, Israel; 8Kanagawa Physicians Association, Kanagawa, Japan; 9 Gaziantep University, Gaziantep, Turkey; 10Diabetes Behavioral Institute, Del Mar, CA, USA

MOSAIc is a multinational 2-year prospective cohort study designed to understand challenges associated with insulin progression in patients with type 2 diabetes (T2D). This analysis describes characteristics of patients who had insulin progression over the 2-year period according to their JO\FHPLF FRQWURO VWDWXV (OLJLEOH SDWLHQWV ZHUH WKRVH ZLWK 7 ' \HDUV ROG DQG XVLQJ LQVXOLQ IRU 3 months with/without other antidiabetes medications seen as part of their usual care, in 18 countries.

Data were measured during patient visits to physicians, semiannually for 2 years. Insulin progression ZDV GH¿QHG DV DQ LQFUHDVH LQ DQWLGLDEHWHV WUHDWPHQW FRPSOH[LW\ *O\FHPLF FRQWURO JRDO DW <HDU ZDV GH¿QHG DV +E$ F 0XOWLSOH LPSXWDWLRQV YLD FKDLQHG HTXDWLRQV ZDV XVHG IRU PLVVLQJ GDWD 'XULQJ the study period, a total of 924 patients had insulin progression. Of those, only 28% achieved glycemic control at Year 2. Those who achieved glycemic control were older, with lower baseline HbA1c; majorities were males, nonsmokers, and those with a family history of diabetes. In addition, 30% of this group still had their HbA1c level above their physician’s stated treatment goal. In conclusion, there are important demographic and clinical differences at baseline among patients with T2D with insulin progression by glycemic control status.

Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at the American Diabetes Association – WK $QQXDO 6FLHQWL¿F 6HVVLRQV -XQH ± 1HZ 2UOHDQV /$ 86$

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BP-08

EFFICACY AND SAFETY BY BASELINE A1C WITH ONCE-WEEKLY DULAGLUTIDE IN THE AWARD PROGRAM 1

THOMAS LEW (PRESENTER ONLY), 2SAMUEL DAGOGO-JACK, 3VIVIAN THIEU, 4 MARIA YU, 3NAN ZHANG, 3DARA SCHUSTER, 3LUIS-EMILIO GARCIA-PEREZ 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2University of Tennessee Health Science Center, Memphis, TN, USA; 3Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA; 4Eli Lilly Canada, Danforth, Canada

Dulaglutide (DU), a once-weekly glucagon-like peptide-1 receptor agonist, was studied in the AWARD clinical trial program in adult patients with type 2 diabetes (T2D) and demonstrated VLJQL¿FDQW KHPRJORELQ $ F $ F UHGXFWLRQ DQG SRWHQWLDO IRU ZHLJKW ORVV To evaluate the efficacy and safety of DU 1.5 mg and DU 0.75 mg in patients with T2D by EDVHOLQH $ F RU ZH FRQGXFWHG D SRVW KRF DQDO\VLV RQ $:$5' WR DQG DW months.

Across 7 studies, 55% to 82% of the DU-treated patients had a baseline A1c < 8.5%, and 18% WR KDG D EDVHOLQH $ F 7KH UDQJHV RI $ F UHGXFWLRQV ZLWK EDVHOLQH $ F DQG 8.5%, respectively, were: DU 1.5 mg: -0.67% to -1.25% and -1.22% to -2.37%; DU 0.75 mg: -0.53% to -1.07% and -1.37% to -2.19%. The A1c reduction from the pooled analysis was greater in patients ZLWK EDVHOLQH $ F WKDQ LQ SDWLHQWV ZLWK EDVHOLQH $ F UHVSHFWLYHO\ '8 PJ and -1.02%; DU 0.75 mg: -1.75% and -0.83%. DU treatments were well tolerated among baseline A1c subgroups.

Across the AWARD program, DU 1.5 mg and DU 0.75 mg demonstrated significant A1c UHGXFWLRQ LQ ERWK VXEJURXSV ZLWK DQ DFFHSWDEOH VDIHW\ SUR¿OH &RPSDUHG WR SDWLHQWV ZLWK EDVHOLQH $ F SDWLHQWV ZLWK EDVHOLQH $ F KDG JUHDWHU $ F UHGXFWLRQ Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at American Diabetes Association – 76th $QQXDO 6FLHQWL¿F 6HVVLRQV -XQH ± 1HZ 2UOHDQV /$ 86$

182

Abstract

BP-09

EFFICACY AND SAFETY BY DURATION OF DIABETES WITH ONCEWEEKLY DULAGLUTIDE IN THE AWARD PROGRAM 1

THOMAS LEW (PRESENTER ONLY), 2BAPTIST GALLWITZ, 3IMRE PAVO, 4 VIVIAN THIEU, 4NAN JIA, 4NAN ZHANG, 4LUIS-EMILIO GARCIA-PEREZ

1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2University of Tübingen, Tübingen, Germany; 3Eli Lilly Regional Operations, Vienna, Austria; 4Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN, USA

Dulaglutide (DU), a once-weekly glucagon-like peptide-1 receptor agonist, was studied in the AWARD clinical trial program in adult patients with type 2 diabetes (T2D) and demonstrated VLJQL¿FDQW KHPRJORELQ $ F $ F UHGXFWLRQ DQG SRWHQWLDO IRU ZHLJKW ORVV To evaluate the efficacy and safety of DU 1.5 mg and DU 0.75 mg in patients with T2D by GXUDWLRQ RI GLDEHWHV 'R' \HDUV DQG \HDUV DQG \HDUV ZH FRQGXFWHG D SRVW KRF analysis on the completed studies, AWARD-1, -2, -5, -6, and -8, at 6 months. AWARD-3 and -4 were not included in the analysis because, due to the population studied, small numbers of patients had DoD \HDUV LQ $:$5' DQG 'R' \HDUV LQ $:$5' Across the 5 studies, the proportions of patients with DU treatment were similar among DoD VXEJURXSV 7KH UDQJHV RI $ F UHGXFWLRQV ZLWK 'R' \HDUV DQG \HDUV DQG \HDUV respectively, were: DU 1.5 mg: -1.19% to -1.54%, -1.16% to -1.56%, and -1.04% to -1.50%; DU 0.75 mg: -0.90% to -1.28%, -0.94% to -1.21%, and -0.82% to -1.38%. The A1c changes were similar from WKH SRROHG DQDO\VLV ZLWK 'R' \HDUV DQG \HDUV DQG \HDUV '8 PJ -1.27%, and -1.17%; DU 0.75 mg: -1.02%, -0.93%, and -0.98%, respectively. The effects on weight were similar among DoD subgroups with both DU doses, respectively. DU treatments were well tolerated among DoD subgroups.

In conclusion, irrespective of DoD, patients treated with DU demonstrate similar A1c reduction, ZHLJKW FKDQJH DQG DFFHSWDEOH VDIHW\ SUR¿OH Disclosures: This study was supported and conducted by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that was presented at the American Diabetes Association – WK $QQXDO 6FLHQWL¿F 6HVVLRQV -XQH ± 1HZ 2UOHDQV /$ 86$

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BP-10

ASSESSING THE ECONOMIC BURDEN OF PATIENTS WITH HYPOGLYCEMIA IN TAIWAN USING THE NATIONAL HEALTH INSURANCE RESEARCH DATABASE (NHIRD) 1

CJ CHANG, 2,3HSIEH AN-TSZ, 5THOMAS LEW, 4BRUCE C.M. WANG, 4 WESLEY FURNBACK; 6WEE TECK NG, 6ALENA STRIZEK 1

Medical Statistics Research Center, Chang Gung University, 2Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan, 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, 4Elysia Group Ltd., Taipei, Taiwan, 5Eli Lilly and Company (Taiwan), Inc., 6Eli Lilly and Company, Indianapolis, IN, USA

Purpose: For patients with type 2 diabetes mellitus (T2DM), hypoglycemia, whether severe RU PLOG FDQ UHVXOW LQ VLJQL¿FDQW FR PRUELGLWLHV LPSDFWLQJ TXDOLW\ RI OLIH 7KHVH LQ WXUQ LQFUHDVH WKH economic burden of the disease. This study aims to quantify the economic burden of hypoglycemia in Taiwan using the National Health Insurance research database (NHIRD), a claims-based dataset encompassing 99% of Taiwan’s population.

Methods: Using the NHIRD 2 million patient sample, the index period ran from 2001 to 2012 with 2000 and 2013 serving as the pre- and post-index periods, respectively. Patients were indexed into the study if they had a diagnosis of T2DM during the index period, had a minimum of 12 months continuous enrollment in their pre- and post-index periods, and did not meet any exclusion criteria.

Patients with a hypoglycemic episode (HE) (defined by ICD-9 code) during the index period were LGHQWL¿HG 0HDQ DQQXDO GLUHFW PHGLFDO FRVWV ZHUH FRPSXWHG IRU HDFK FRKRUW GXULQJ WKH VWXG\ SHULRG A matched study cohort of patients with T2DM which did not have a HE was also identified and matched 4:1 on index date, age, sex, and the Charlson Comorbidity Index (CCI) to the HE cohort for comparison.

Results: :H LGHQWL¿HG SDWLHQWV ZLWK LQFLGHQW +(V EHWZHHQ DQG 0HDQ DQQXDO direct medical costs for patients with and without incident HEs were NT$173,701 and NT$93,275, respectively. The incremental mean annual direct costs between the HE cohort and without HE cohort was NT$80,426. Incremental costs between the HE and non-HE cohorts were driven by higher mean annual inpatient costs (NT$42,654), outpatient costs (NT$31,718), and emergency department costs (NT$6,055).

Conclusion: The economic burden of Taiwanese T2DM patients with HEs is substantially higher than T2DM patients not experiencing HEs. The introduction of new diabetic therapies with improved +( VLGH HIIHFW SUR¿OHV FRXOG UHGXFH WKH LQFLGHQFH RI +(V WKXV GLPLQLVKLQJ KHDOWK V\VWHP FRVWV DQG improving the health outcomes of Taiwanese patients.

184

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186

th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Memo

Abstract

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th Annual Meeting of April 8-9, 2017 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Memo

Abstract

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