108年年會

Contents Floor Plan of Conference Rooms ........................................................................................... 2 Daily Program Schedule........................................................................................................... 6 Opening Remarks ...................................................................................................................... 8 Board of Directors .................................................................................................................... 10 Sponsors ....................................................................................................................................11 Moderator & speaker ............................................................................................................. 12 Agenda ...................................................................................................................................... 14 Abstract PLȈPlenary Lecture (1-4) ................................................................................................. 35 DAROC-TADEȈDAROC-TADE Joint Symposium....................................................... 41 MTPȈMeet the Professor (1-2) ....................................................................................... 45 SDȈSymposium-Diabetes (1-7) ........................................................................................ 46 SEȈSymposium-Endocrine (1-7) ..................................................................................... 65 YLȈBasic Research and Young Investigator Research Lecture ........................................ 85 LSȈLunch Symposium (1-13) ODȈOral Presentation-Diabetes (1-6) .............................................................................. 91 OEȈOral Presentation-Endocrine (1-6) ............................................................................ 97 APȈ2019 Award .............................................................................................................. 103 PDȈPoster Presentation-Diabetes (1-26) ........................................................................ 107 PEȈPoster Presentation-Endocrine (1-35) ...................................................................... 134 BPȈExhibitor Poster Display (1-5) ................................................................................ 180

1

40

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

ѯτ୾ርཽឋϜЗΚዃ҂८შ

The

2

ѯτ୾ርཽឋϜЗΡዃ҂८შ

Floor Plan of Conference Rooms

3

ѯτ୾ርཽឋϜЗήዃ҂८შ

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

4

5

40

The

ѯτ୾ርཽឋϜЗѳዃ҂८შ

Floor Plan of Conference Rooms

5

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Ϝ๽Җ୾ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬Ᏹཽ ಒ 14 ۪ಒ 1 ԪཽসτཽᄳᏱ೛ःଇཽ ࿾ҭߓ March 30, 2019 (Saturday) Room 101

Room 301

Room 401

Room 402AB

Room 402CD

Room 202

Room 203

600 ΢

220 ΢

220 ΢

200 ΢

200 ΢

80 ΢

80 ΢

LS6 ߢල੬௧ւஷ

LS7 ᎄ࿆

ȁȁȁȁȁDAROC-TADEȁ(Room 101) DAROC-TADE Joint Symposium лࡼ΢Ȉ೩ඐ㠈ȃ‫ݔ‬ਣ໌ȃ؈ࡧ኉ȃе‫ݾ‬ϰȁ ᅌᗀ޲Ȉ‫ݔ‬პᘅȃ‫ݔ‬з៤ȃ؄ਥཐȃചવኌ

08:00-12:00

12:00-13:00

LS1 Լ᡺‫ٺ‬

LS2 ᓷؔ‫ݎ‬

LS3 ᒜ‫ڸ‬ᒜ኉

13:20-13:30

LS4 Ѕ๽

LS5 जՕւᅮ

Opening (Room 101)

13:30-14:15

PL1ȁPlenary Lecture-1 (Room 101) лࡼ΢Ȉ೩ඐ㠈ȁᅌᗀ޲ȈPhilip S. Tsaoȁ

14:15-15:00

PL2ȁPlenary Lecture-2 (Room 101) лࡼ΢Ȉ෇߈।ȁᅌᗀ޲ȈDolores M. Shobackȁ

15:00-15:20

15:20-17:00

Break (Poster Stand -3 Floor Walkway) SD-1

SE-1

SE-2

2019 Taiwan DM Atlas and Registry

KES and ESROC Joint Symposium

AI in New Generation of Medicine

лࡼ΢Ȉ೩ඐ㠈 ȁȁȁȁᔝ‫ݎ‬঩ ȁȁȁȁեᐢ೾ ᅌᗀ޲Ȉ೩‫ע‬Ԛ ȁȁȁȁ‫ݔ‬ਣ໌ Edward J Boyko

SD-2

лࡼ΢Ȉ෇߈। лࡼ΢Ȉ྇୊ി лࡼ΢Ȉٛᓃይ Eun Jig Lee ȁȁȁȁച‫ؙ‬໫ ȁȁȁȁചᄹᆌ ȁȁȁȁ؈ࡧ኉ ᅌᗀ޲Ȉച‫ي‬፲ ᅌᗀ޲ȈരҴԚ ᅌᗀ޲Ȉചߝ໸ Hossein Gharib ȁȁȁȁ؈࠶ዯ ȁȁȁȁ‫݁ݔ‬኉ Young-Kee Shong ȁȁȁȁചং࿋ Daisuke Yabe

MTP-D

MTP-E

Meet the ProfessorDiabetes

Meet the ProfessorEndocrine

OE Oral PresentationEndocrine

OD Oral PresentationDiabetes

17:00-18:00 лࡼ΢Ȉ༂ऊ൞ лࡼ΢Ȉጿջང лࡼ΢Ȉᙐም‫ ع‬лࡼ΢Ȉᗃ݃ঢ় ȁȁȁȁе‫ݾ‬ϰ ȁȁȁȁࢺΛϧ ᅌᗀ޲Ȉ ᅌᗀ޲Ȉ David G. Armstrong Dolores M. Shoback ȁȁȁȁቔቄ࣏ ȁȁȁȁചఽֆ

18:00-21:00

6

SE-3

Diabetic Kidney Update of Adrenal Disease: An Tumors Update

Welcome Dinner (Conference Room 101)

лࡼ΢Ȉചో਷ ȁȁȁȁ༂Љಉ ᅌᗀ޲Ȉង।Н ȁȁȁȁ஼ਤၗ ȁȁȁȁеᆉ࿘

Daily Program Schedule

March 31, 2019 (Sunday) Room 101

Room 301

Room 401

Room 402AB

Room 402CD

Room 203

600 ΢

220 ΢

220 ΢

200 ΢

200 ΢

80 ΢

SD3 SD-4 SE-4 SE-5 SD-5 Prof. Gerald DM Care in the Thyroid Disease Update in Application of Reaven Memorial Older People in Pregnancy Pituitary Disease AI in Diabetes: Symposium From Diagnosis to Management лࡼ΢Ȉ೩ඐ㠈 лࡼ΢Ȉചᄹᆌ лࡼ΢Ȉചࡧႁ лࡼ΢Ȉဩਐᖑ ȁȁȁȁᔝ‫ݎ‬঩ ȁȁȁȁചఽֆ ȁȁȁȁ‫׊ݔ‬ႁ ȁȁȁȁ஼ኋ‫ ܇‬лࡼ΢Ȉ྇୊ി ȁȁȁȁᗃς݃ ȁȁȁȁ༂࡛ᄀ ȁȁȁȁᗃ݃ঢ় Ida Chen ȁȁȁȁጿзᐪ 08:00-09:30 ᅌᗀ޲Ȉեᐢ೾ ᅌᗀ޲Ȉ‫ݔ‬ኋឮ ᅌᗀ޲Ȉࢋ๣ᇉ ᅌᗀ޲Ȉ‫ݔ‬ςല ȁȁȁȁരहડ ȁȁȁȁ؄࠶኉ ȁȁȁȁ༂֘ᆃ ȁȁȁȁ྇ς҅ ᅌᗀ޲Ȉ֕ᅖത ȁȁȁȁ‫ؖ‬኉݀ Masato Odawara Hossein Gharib Eun Jig Lee ȁȁȁȁ༂ఽ߹ ȁȁȁȁ᎓ఃྜ ȁȁȁȁ‫ۤؖ‬ᓘ ȁȁȁȁᇥ ⢿ ȁȁȁȁе‫ڄ‬Н ȁȁȁȁೆ৩ㅉ ȁȁȁȁ֕ఄ໱ Peter Reaven Philip S. Tsao

09:45-10:30

ȁPL3ȁPlenary Lecture-3 (Room 101)

General Assembly ཽসτཽ (Room 101)

12:00-12:10

Group Picture ཽসτӬྲ (1st Floor Square)

13:30-14:15

‫ ې‬ଋ ਫ ี ଅ ೏ 2 ዃൣ‫ژ‬೏ ‫ې‬ଋีଅਣ໣ 3/30 7:30-16:00 3/31 7:30-11:00 ႊਣณ‫ݳ‬ ୥ђᒶᖟ !

лࡼ΢ȈೆҴҖȁᅌᗀ޲ȈDavid G. Armstrong

10:30-12:00

12:10-13:10

ᒶᖟൣ‫ژ‬

Break (Poster Stand -3 Floor Walkway) ੖ൣ৥ұຠϸ PD лࡼ΢Ȉ‫ݔ‬ਣ໌ȃе߹ᑺȃ؄࡛ᑺ PE лࡼ΢Ȉងีྶȃߚ୊ઊȃ֕ஏᆋ

09:30-09:45

LS8 ᒜ๽

LS9 ᗊᒜຆ

LS10 ᒜ‫ڸ‬ᒜ኉

PL4ȁPlenary Lecture-4 (Room 101)

14:15-14:45

LS11 ഻ઊ

LS12 जા٩Ѽ

лࡼ΢Ȉ‫ݔ‬ϧ኉ȁᅌᗀ޲Ȉ‫׊ݔ‬ႁ

Break (Poster Stand -3 Floor Walkway) SD-6 Prof. Ida Chen Honorary Symposium

лࡼ΢Ȉ೩ඐ㠈 ȁȁȁȁᔝ‫ݎ‬঩ ȁȁȁȁեᐢ೾ ȁȁȁȁ‫ؖ‬኉݀ ȁȁȁȁᅫ ࢎ 14:45-17:00 ȁȁȁȁೆҴҖ ᅌᗀ޲ȈೆҴҖ ȁȁȁȁࢺΛϧ ȁȁȁȁ؄࠶኉ ȁȁȁȁ᎓ఃྜ ȁȁȁȁ֕ఄ໱ ȁȁȁȁೆ৩ㅉ ȁȁȁȁ֕ᑠԋ ȁȁȁȁᇥ ⢿ Jerome Rotter Ida Chen

SD-7 DM Glucose Treatment Guideline: An Update

౪ ᆀ ‫ٲ‬ ᒶᖟ‫ٲ‬໷

SE-6 Update in Osteoporosis

LS13 ᙅ‫ٿ‬

ስಊІ‫׺‬ಊ ཽসτཽ ๗‫ࡤ؃‬Ⴒॏ 12:00-14:30 202 ࡊ ɏ ‫ཽڎ‬ᔗᒶ౪ ᆀ‫ٲ‬΢኶ϛ ӤȂཽ፝স ੽ཏഷӼѠ ୽ᒶ΢኶Ȅ

SE-7 YL Radiofrequency Basic Research Ablation in and Young Endocrine Disease: Investigator Thyroid and Others Research Lecture

лࡼ΢Ȉጿзᐪ лࡼ΢Ȉጿջང лࡼ΢Ȉе‫ڄ‬Н лࡼ΢Ȉೆ৩ㅉ ȁȁȁȁ༂ऊ൞ ȁȁȁȁ؄߫቉ ȁȁȁȁ஼Љ໚ ȁȁȁȁ༂࡛ᄀ ȁȁȁȁ؈ࡧ኉ ȁȁȁȁ྇୊ി ȁȁȁȁٛᓃይ ᅌᗀ޲Ȉ؄҅ϰ ᅌᗀ޲Ȉߚ୊ઊ ᅌᗀ޲Ȉе‫ݾ‬ϰ ᅌᗀ޲Ȉᒄᘺৡ ȁȁȁȁԨ‫ע‬Ꮫ ȁȁȁȁ༂ӑύ ȁȁȁȁᗃ࿳߭ ȁȁȁȁࢺ㦬ᄕ ȁȁȁȁጿջང Jung Hwan Baek ȁȁȁȁ؄҅ϰ Jon Y. Takemoto

໡ ಊ 14:45-17:00 205 ࡊ

7

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

౪‫ߞٲ‬यມ ө՞ཽসυςȃӒҢȈ ࢍཹ߇໡‫ޠ‬ήУЉȂ᠎ߕө՞ཽসυςӒҢ‫ٿ‬ѯі୥ђϜ๽Җ୾ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬ Ᏹཽಒ 14 ۪ಒ 1 ԪཽসτཽȊؑԒഇႇԒཽ‫ޠ‬ᐡཽȂᏱཽԋ௷ΚЉљ‫ޠ‬Ᏹ೛ࣁ୞Ȃ ᡲτঢ়ರ᠚୾ϲѵ஠ঢ়Ᏹ޲ᅌᗀȂჃᓿτঢ়ᑗ྄୥ᇅଇ፤ȃϸ‫ٵ‬စᡜȂ෉ࡠཽসউഎ ૗ᕖூഷུഷ᝙ີ‫ࣻޠ‬ᜱᚃᕜ‫ޤ‬ᜌІ‫׭‬೛Ȃᔗң‫ژ‬ᖞ‫੿ט‬΢ྲៗȂ‫ܗ‬Жึः‫ف‬РӪȂ ‫ٯ‬ᘘ৥୾ርຝഐȄ ՅџԒ᝱റጢᒯΠΚᐍԒ‫ࡿޠ‬Ж‫ޏ׾‬ϏձȂଷΠ‫ྲٸ‬ഷུ ADA І EASD ࡛ឋȂ ᎍ࿌ঔҔȶ2018-2019 ᑦ‫੿׎‬ᖞ‫ྲט‬ៗࡿЖȷȂ‫ש‬উη‫׈‬ԚΠȶ2019 ѯᢋᑦ‫੿׎‬๬᠛ ੿ᡑᖞ‫ྲט‬ៗࡿЖȃׂ৓ᑦ‫ྲ੿׎‬ៗКьȃ2019 ѯᢋᑦ‫੿׎‬ՃԒఋထᖞ‫ྲט‬ៗࡿЖȷ ཽসউѠпαᆪίၸࣻᜱၦਠȇѫѵѣ໡ȶᑦ‫੿׎‬ઢစ੿ᡑӔᜌϊಣཽឋȷ෉ࡠ஡ഷ ུ‫ޠ‬ᑦ‫ࣻ੿׎‬ᜱስ஀‫ޤޠ‬ᜌȃः‫ف‬ழ๞ཽসȄ ϭԒཽস፤Н‫׺‬ጉӔॏԥ 73 ጖Ȃπᓟൣ֚ 12 ጖ȃᏪൣ৥ұ 61 ጖ȄԒཽ‫ޠ‬ᑦ‫׎‬ ੿࿾ҭϜȂ‫ש‬উ੬րԋ௷өᑦ‫ࣻ੿׎‬ᜱዦߟስ஀‫ޠ‬ឋᚡȂ஡өስ஀‫ໍུޠ‬৥֖౫๞ཽ সȂєࢃȈ 2019 Taiwan DM Atlas and RegistryȃDiabetic Kidney Disease: An Updateȃ DM Care in the Older PeopleȃApplication of AI in Diabetes: From Diagnosis to ManagementȃDM Glucose treatment: An update ᇅፐఁᏱཽӬᒳፐఁ፟โःଇཽȃः‫ف‬ ॏฬዪᓿԚ‫ߓึݏ‬Ȅ ϭԒԒཽ࿾ҭϜ‫ש‬উ੬րԋ௷ Prof Gerald M Reaven ‫ޠ‬ख‫܉‬ःଇཽȂӔӤᛅ‫܉‬Ӷ џԒߒႇз‫ޠ‬ѭϞᆌτᏱ Reaven ఁ௳ȄӤਣȂ‫ש‬উηԋ௷Πདᗃ൶஥ Prof Ida Chen Ᏹ೛ःଇཽȂηདᗃԃႇџ኶ΫԒᄈѯᢋᑦ‫ࣩ੿׎‬Ᏹ೛ः‫ޠف‬ЖስᇅଔᝧȄ དᗃ‫ܛ‬ԥཽসυςӒҢпІີᇾ୥ђҐᏱཽᇅϲϸ‫ݫ‬ᏱཽϟԒ࡚౿ཽȄඐ㠈ᐋӉ ‫ڎ‬ӉϳԒ౪‫֊ߞٲ‬஡֚ΚࢳဤȂདᗃ౪ᆀ‫ٲ‬ȃཽসউ‫ޠ‬МࡼᇅჃᓿȃདᗃ‫ݔ‬ਣ໌બਫ ߞȃӼ՞୚બਫߞᇅཽଡ଼Ӥϧউ‫ڟޠ‬ ֆȂᡲ‫ש‬উ໸ւ‫׈‬ԚӼ໷२τ٩โ࿭ ‫ޠ‬ϏձӉଡ଼Ȃ‫ש‬উ஡ϏձԚ‫ݏ‬ཋᐍԚ ьȂණ‫ٽ‬τঢ়ࡿҔȄ ིણτঢ় ٙᡞୋஷȂ҂ԋ‫ץ‬዆Ȃ τཽ༬ᅗԚѓȄ ަყ‫ݳ‬΢Ϝ๽Җ୾ᑦ‫੿׎‬Ᏹཽ ౪‫ߞٲ‬ȁȁȁȁȁȁȁȁᙲα ȁȁȁȁȁȁȁ 108 Ԓ 3 У 30 С 8

Opening Remarks

౪‫ߞٲ‬यມ ᠎ߕө՞ཽস୥ђ 108 Ԓ‫ޠ‬ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬ᏱཽԒཽІᏱ ೛ःଇཽȄҐԒ࡚τཽҦᑦ‫੿׎‬ᏱཽлᒳȂϲৡᙵ൳‫׈‬ᐍȄϲ ϸ‫ݫ‬Ᏹཽᗝ፝୾ር‫ޤ‬ӫ‫ ޠ‬Dolores Shoback ఁ௳ȃ‫׊ݔ‬ႁఁ௳ȃ Hossein Gharib ఁ௳ᐋӉ Plenary lectureȃMeet-the-Professor ᗀ৵Ȃ ή՞ఁ௳‫ޠ‬Ᏹ೛ోᎵІᖞ‫ט‬စᡜᙵ൳ȂཽসউѠпҦуউ‫ޠ‬ᅌᗀϜԥ࡟Ԃ‫ޠ‬ᏱಭȄϲ ϸ‫ݫ‬Ᏹཽԋ௷‫ޠ‬ःଇཽӔԥΝൠȂϸր࣐Ϝᗻϲϸ‫ݫ‬Ᏹཽһࢻ ( ᗻ୾ᇅཽѵᇾ࣐ϲϸ ‫ݫ‬Ᏹཽ౪‫ ߞٲ‬Eun-Jig Lee ఁ௳І Young-Kee Shong ఁ௳ )ȃ΢Ϗහኌȃ๬αသ੾੿ȃҧ ‫ޒ‬သ੾੿ᇅᛅѺȃဟ࠮ᡞ੾੿ȃଽ፵౶ᚭȃਰᚃᔯࢦᇅ‫ݾ‬ᕜ๊лᚡȄ‫ܛ‬ᗝ፝‫ޠ‬ᅌᗀ޲ Ілࡼ΢എ࢑ॷۨΚࡿ‫ޠ‬஠ঢ়ȂϲৡᆡீѠ෉Ȅϲϸ‫ݫ‬Ᏹཽ஡ܼԒཽ෉໣Ӥਣя‫ޏ‬ȶׂ ৓ᇅ౱ࡤҧ‫ޒ‬သ੾੿ᖞ‫ט‬ຩ‫ݾ‬КьȷȂѠпණ‫ཽٽ‬সᖞ‫ט‬୥ՄȄѫѵȂᑦ‫੿׎‬Ᏹཽԋ ௷ ‫ ޠ‬Plenary lectureȃ ख ‫ ܉‬Prof. Gerald Reaven І ൶ ི Prof. Ida Chen ‫ ޠ‬Symposiumȃ ‫ڐ‬уөϛӤлᚡ‫ ޠ‬symposiumȃཽস‫ޠ‬πᓟ‫ܗ‬Ꮺൣ፤Нൣ֚ȃ᛿ࣩӤϧԋ௷‫ ޠ‬Lunch symposium ๊ηഎ࢑ᆡߜ࿳ϸȂࣻ߭‫ܛ‬ԥ‫ཽޠ‬সഎ૗஋Ӷ೼ൠᏱ೛౿৞ϜԞᛧᅗᅗȄ ᙲԫདᗃ‫ܛ‬ԥлࡼ΢Іᅌᗀ޲ȃᑦ‫੿׎‬Ᏹཽ೩ඐ㠈౪‫ߞٲ‬ȃϲϸ‫ݫ‬Іᑦ‫੿׎‬Ᏹཽ‫ڎ‬ ཽ‫ޠ‬બਫߞȃ୚બਫߞȃબਫȃ‫ܛ‬ԥ‫᜔ޠ‬ֆ޲Ȃ‫؂‬ᗃᗃ‫ܛ‬ԥཽস‫ޠ‬୥ϡᇅМࡼȄ‫ཽڎ‬ಒ 13 ۪౪ᆀ‫ٲ‬Ӊ෉֊஡۪ᅗȂϭԒ‫ཽޠ‬সτཽ‫ש‬উ஡ණяήԒ‫ޠٿ‬ᏱཽϏձൣ֚Ȅᙲԫ དᗃ‫ܛ‬ԥཽস‫ޠ‬МࡼȂᏱཽ឵ܼӓᡞཽসȂ෉గಒ 14 ۪౪ᆀ‫ٲ‬ᒶᖟΚϹ໸ւȂτঢ়ყ ๗ӬձȂ࣐ѯᢋϲϸ‫ݫ‬ȃᑦ‫੿׎‬ȃུചхᗃ੾੿ϟᖞ‫ט‬ຩᕜІᏱ೛ः‫ึف‬৥ՅևΩȄ ᙲણ τঢ়ٙᡞୋஷȃ࿳‫ٲ‬ԄཏȄ ަყ‫ݳ‬΢Ϝ๽Җ୾ϲϸ‫ݫ‬Ᏹཽ ౪‫ߞٲ‬

108 Ԓ 3 У 30 Сȁȁȁȁȁȁ 9

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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

10

ᔝ‫ݎ‬঩ Tong-Yuan Tai

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

Sponsors

The Endocrine Society and the Diabetes Association of the R.O.C (Taiwan) Would Like to Recongnize the Following for Their Support of the 40th Annual Meeting Ȟ‫์ྲٸ‬დ௷‫ז‬ȟ Ωτშਫԥ४ϵѨ

The Leader Book Company Ltd.

Ѕ๽Ң‫׭‬ᚃ᛿޷ӌԥ४ϵѨ

Orient EuroPharma Co., Ltd.

ѯᢋҥᜟᇨ᛿޷ӌԥ४ϵѨ

Taiwan Tanabe Seiyaku Co., Ltd.

ѯᢋԋὺ߭ԥ४ϵѨ

Ascensia Diabetes Care Taiwan, Ltd.

ѯᢋԼ᡺‫੉ٺ‬ੀᑲ޷ӌԥ४ϵѨ

Boehringer Ingelheim Taiwan Ltd.

ѯᢋ‫ݢ‬ҥ᛿ࠣϏཿ޷ӌԥ४ϵѨ

Takeda Pharmaceuticals Taiwan, Ltd.

ѯᢋࡷՇ޷ӌԥ४ϵѨ

Bayer Taiwan Co., Ltd.

ѯᢋ৥㝛ᚃᕜᏣ؆ԥ४ϵѨ

IKI Medical Co., Ltd.

ѯᢋᒜ‫ڸ‬ᒜ኉᛿ࠣ޷ӌԥ४ϵѨ

Novo Nordisk Pharma (Taiwan) Ltd.

ѯᢋᒜ๽޷ӌԥ४ϵѨ

Novartis (Taiwan) Co., Ltd.

ѯᢋᙅ‫޷ٿ‬ӌԥ४ϵѨ

Eli Lilly Company (Taiwan)

ԋջҢᚃ޷ӌԥ४ϵѨ

AmCad BioMed Corporation

‫ݳ‬୧ઊ඾Ң޷ӌԥ४ϵѨѯᢋϸϵѨ

IPSEN Pharma Taiwan Branch

जՕւᅮୋஷ޷ӌԥ४ϵѨ

Alere Taiwan Alere Health Corp

ज୧‫ٴ‬ஊ޷ӌԥ४ϵѨѯᢋϸϵѨ

Abbott Laboratories Services Corp. Taiwan Branch

ज୧ᓷؔ‫ݎ‬᛿ኆ޷ӌԥ४ϵѨѯᢋϸϵѨ

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

഻ઊҢ‫޷׭‬ӌԥ४ϵѨ

Chuang Yi Biotech

ུђ‫ۄ‬୧जા٩Ѽᚃ᛿ԥ४ϵѨѯᢋϸϵѨ

A.Menarini Singapore Pte. Ltd., Taiwan Branch

პ኉᛿ࠣӍཿ޷ӌԥ४ϵѨ

Char Deh Drugs Enterprise Co., Ltd.

ᇄᢋߢල੬௧ւஷ޷ӌԥ४ϵѨ

AstraZeneca Taiwan Limited

ዊⵯ኉ᚃᕜᏣ؆޷ӌԥ४ϵѨ

23(' $VLD 3DFL¿F &R /WG

ᎄ࿆τ᛿ኆ޷ӌԥ४ϵѨ

3¿]HU 7DLZDQ /WG

ᗊᒜຆ޷ӌԥ४ϵѨ

6DQR¿ 7DLZDQ &R /WG

ᛴЫτ᛿ኆ޷ӌԥ४ϵѨ

Roche Products Ltd. 11

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

лࡼ΢ȃᅌᗀ޲ӗߓ ( ѵᇾ ) Daisuke Yabe, M.D.,Ph.D.

Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan; Division of Diabetes and Endocrinology, Kansai Electric Power Medical Research Institute, Kobe, Japan

David G. Armstrong, DPM, M.D., Ph.D.

Professor of Surgery, Keck School of Medicine USC; Department of Surgery

Dolores M. Shoback, M.D.

Professor of Medicine in Residence University of California, San Francisco

Edward J. Boyko,M. D.,M.P.H.

Professor, Department of Medicine, Adjunct Professor, Department of Epidemiology, Adjunct Professor, Department of Health Services, University of Washington

Eun Jig Lee, M.D., Ph.D.

President of Korean Endocrine Society, Professor of Endocrinology; Chairman, Department of Medicine; Yonsei University, College of Medicine; Chief Physician, Department of Medicine; Severance Hospital

Hossein Gharib, M.D., MACP, MACE

Professor of Medicine, Mayo Clinic College of Medicine; Past President, American Association of Clinical Endocrinologists; Past President, American Thyroid Association

Jerome I.Rotter, M.D.

Professor of Pediatrics, UCLA School of Medicine Professor of Human Genetics, UCLA School of Medicine; Director, Institute for Translational Genomics and Population Sciences, LABioMed/Harbor-UCLA; Director, Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Harbor-UCLA

Jon Y. Takemoto, Ph.D.

Professor of Biology; Department of Biology, Utah State University

Jung Hwan Baek, M.D., Ph.D.

Professor of Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea President of the Korean Society of Thyroid Radiology

Masato Odawara, M.D.

The Department of Diabetes,Endocrinology,Metabolism and Rheumatology,Tokyo Medical University

Peter Reaven, M.D.

Professor of Clinical Medicine; University of Arizona; Phoenix, Arizona

Philip S. Tsao, Ph.D.

Professor of Medicine (Cardiovascular Medicine); Stanford University School of Medicine Associate Chief of Staff for Precision Medicine; VA Palo Alto Health Care System Director; VA Palo Alto Epidemiology Research and Information Center (ERIC) for Genomics Co-Principal Investigator; Million Veteran Program

Yii-Der Ida Chen, Ph.D.

Professor of Pediatrics and Medicine, UCLA; Director, Biochemistry, Molecular Phenotyping, and Microarray Laboratory, ITGPS, LA Biomed/Harbor-UCLA

Young-Kee Shong, M.D., Ph.D.

Professor, Asian Medical Center, University of Ulsan, Seoul, Korea ( ‫ ྲٸ‬First name Ԇҕ໸‫) ז‬

12

Moderator & speaker

лࡼ΢ȃᅌᗀ޲ӗߓ ( ୾ϲ ) е‫ڄ‬Н ା໱ߞ۹ᚃଲ

೩‫ע‬Ԛ ଓყ‫ݳ‬΢୾ঢ়ፐҢः‫ف‬ଲထᡞୋஷऌᏱः‫ܛف‬

е‫ݾ‬ϰ ᇄτᚃଲϲऌഌхᗃϲϸ‫ݫ‬ऌ

೩ඐ㠈 ᇄϜᄹҖᖃᚃଲ

е߹ᑺ ᇄϜᄹҖᖃᚃଲϲϸ‫ུݫ‬ചхᗃऌ

ച‫ؙ‬໫ ᇄᢋτᏱஆӱᡞᄳ೗ҪᡞᚃᏱः‫ܛف‬

еᆉ࿘ ህϧτᏱߤ೪ᚃଲ‫׎ݫ‬ഌ

ച‫ي‬፲ ஆ໫ߞ۹ᚃଲΚૢѵऌ

Ԩ‫ע‬Ꮫ ା໱ᄹᖃུചхᗃऌ

ചߝ໸ ήॗᖃᚃଲ๬᠛ϲऌ

եᐢ೾ ᇄіᄹҖᖃᚃଲ

ചࡧႁ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

֕ஏᆋ ᇄτᚃଲϲऌഌхᗃϲϸ‫ݫ‬ऌ

ചং࿋ ѯᢋ΢ϏහኌᄃᡜࡊȃᇄᢋτᏱҢ‫ޑ‬ᐡႬ‫ق‬

֕ఄ໱ Min-Shung Wu Diabetes Clinic

ചવኌ ᄕஆᚃᕜଓყ‫ݳ‬΢ഫ෬ஆ࿝ఁᚃଲ

֕ᅖത ๽ᆉ໵ᆓᄳ๽ᆉୋஷᖃစ౪

ചో਷ ᇄіᄹҖᖃᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

֕ᑠԋ ߇ጹཐᔽᚃᏱϜЗ

ചఽֆ Ϝ୾ᚃ᛿τᏱߤ೪ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

؄҅ϰ ᇄτᚃଲϲऌഌ

ചᄹᆌ ା໱ߞ۹ख‫܉‬ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

؄߫቉ ࿳߀ᚃଲ

രҴԚ

؄࠶኉ ᇄϜᄹҖᖃᚃଲϲϸ‫ུݫ‬ചхᗃऌ

രहડ Ϝ୾ᚃ᛿τᏱߤ೪ᚃଲϲऌഌུചхᗃऌ

؄࡛ᑺ ήॗᖃᚃଲϲϸ‫ུݫ‬ചхᗃऌ

෇߈। ᇄτᚃଲϲऌഌ

؄ਥཐ ᄕஆᚃᕜଓყ‫ݳ‬΢ഫ෬ஆ࿝ఁᚃଲ

༂Љಉ ୾੏ᆤӬᚃଲϲϸ‫ུݫ‬ചхᗃऌ

؈࠶ዯ ᇄᢋ΢Ϗහኌᄃᡜࡊ഻ᒳ΢

༂ӑύ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

؈ࡧ኉

Ϝ๽Җ୾ᑦ‫੿׎‬ፐఁᏱཽಒΥ۪౪‫ߞٲ‬ ᄕϾஆ࿝ఁᚃଲᑦ‫੿׎‬ୋஷ e ଲ

ᇄτ΢ϏහኌᇅᐡᏣ΢ः‫ف‬ϜЗлӉ ᇄτၦϏ‫ق‬ᇅႬᐡ‫ق‬੬ဓఁ௳

༂֘ᆃ ᇄіᄹҖᖃᚃଲུചхᗃऌ

‫ۤؖ‬ᓘ ᇄϜᄹҖᖃᚃଲϲϸ‫ུݫ‬ചхᗃऌ

༂࡛ᄀ ϜύᚃᏱτᏱߤ೪ᚃଲ

‫ؖ‬኉݀ ‫ؖ‬኉݀ຩ‫ܛ‬ȃϜύᚃଲ

༂ऊ൞ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌІᕋᎵ‫ݾ‬ᕜऌ

ٛᓃይ ା໱ᚃᏱτᏱᚃᏱଲȃା໱ᚃᏱτᏱߤ೪ᚃଲ

༂ఽ߹ හྦҢᚃऌ‫޷׭‬ӌԥ४ϵѨ

‫ݔ‬ςല ᇄіᄹᖃ੿౪ᔯᡜഌ

྇ς҅ ᇄτᚃଲઢစѵऌ

‫ݔ‬ϧ኉ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

྇୊ി ᇄτᚃᏱଲᖞ‫ט‬ᚃᏱः‫ܛف‬

‫ݔ‬з៤ ᄕϾஆ࿝ఁᚃଲϲऌഌ

ဩਐᖑ ़ਹᓟӌ࣐৿ख‫܉‬ᚃଲ

‫׊ݔ‬ႁ ᇄіᄹҖᖃᚃଲ

ᅫ ࢎ ୾ঢ়ፐҢः‫ف‬ଲ / ထᡞୋஷऌᏱः‫ܛف‬

‫݁ݔ‬኉

ା໱ᚃᏱτᏱᚃᏱଲ ᇥ ⢿ ህτᚃᏱ‫قق‬лӉᄳህτᚃଲུചхᗃऌлӉ ା໱ҀҴτӤᚃଲȞ‫ې‬ଋାᚃစᕋȟུചхᗃϲϸ‫ݫ‬ऌ

‫ݔ‬ਣ໌ ᇄϜᄹҖᖃᚃଲାឮᚃᏱϜЗ

ቔቄ࣏ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

‫ݔ‬პᘅ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

ጿзᐪ ਐᑺᚃଲུചхᗃऌІᕋᎵ‫ݾ‬ᕜऌ

‫ݔ‬ኋឮ ୾੏ᚃᕜଓყ‫ݳ‬΢୾੏ᆤӬᚃଲ

ጿջང ᇄτᚃଲϲऌഌІሊ‫ݎ‬ຩ‫ܛ‬

ߚ୊ઊ ᇄτᚃଲϲऌഌхᗃϲϸ‫ݫ‬ऌ

᎓ఃྜ ଞӅᚃ৲

ࢋ๣ᇉ ᇄτᚃᏱଲϲऌഌ

ᒄᘺৡ ା໱ᚃᏱτᏱߤ೪ᚃଲϲϸ‫ུݫ‬ചхᗃϲऌ

ࢺΛϧ ήॗᖃᚃଲ‫ݙ‬ύϸଲϲϸ‫ུݫ‬ചхᗃऌ

ᔝ‫ݎ‬঩ ᇄіϧᔽᚃଲ

ࢺ㦬ᄕ Ԛτᚃଲϲऌഌϲϸ‫ུݫ‬ചхᗃऌ

ᗃς݃ ϜύᚃଲЗ᠛ϲऌ

஼Љ໚ ᇄτᚃଲϲऌഌ

ᗃ݃ঢ় ᄕϾஆ࿝ఁᚃଲུചхᗃऌ

஼ਤၗ ᇄτᚃଲኈ჌ᚃᏱഌ

ᗃ࿳߭ ϏःଲҢᚃ‫ܛ‬

஼ኋ‫ ܇‬Ϝ୾ᚃ᛿τᏱߤ೪ᚃଲϲऌഌ

ᙐም‫ ع‬ᇄі଼୎ᚃଲ

ೆҴҖ ᇄτᚃଲϲऌഌ

ង।Н ᇄіᄹҖᖃᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

ೆ৩ㅉ ‫ݔ‬πߞ۹ᚃଲϲϸ‫ݫ‬ᄳུചхᗃऌ

ងีྶ ሊ‫ݎ‬ᖓӬຩ‫ܛ‬ᚃៗഌлӉ ( ‫ۘྲٸ‬Ы์ฬ໸‫) ז‬

13

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Ϝ๽Җ୾ϲϸ‫ݫ‬ᄳᑦ‫੿׎‬Ᏹཽ ಒ 14 ۪ಒ 1 ԪཽসτཽᄳᏱ೛ःଇཽ С෉ȈҖ୾ 108 Ԓ 3 У 30-31 С ӵᘉȈѯτᚃଲ୾ርཽឋϜЗ

March 30, 2019 Ȫ101 Roomȫ Time

PL1: Plenary Lecture 1 Topic

Speaker

೩ඐ㠈

13:30-13:35 OPENING PL1

13:35-14:15 GENETIC DETERMINANTS OF CARDIOMETABOLIC DISEASE

March 30, 2019 Ȫ101 Roomȫ Time

Philip S. Tsao

Topic

Speaker

Ȫ101 Roomȫ Time

Dolores M. Shoback

Topic

Speaker

Ȫ101 Roomȫ Time

David G. Armstrong

14

ೆҴҖ

PL4: Plenary Lecture 4 Topic

Speaker

13:30-14:15 HISTORY OF ENDOCRINOLOGY--THE NOBEL LAUREATES

Moderator ‫ݔ‬ϧ኉

13:30-13:35 OPENING PL4

Moderator ೆҴҖ

13:35-14:15 DIABETIC FOOT: THE GLOBAL STATE OF PLAY

March 31, 2019

෇߈।

PL3: Plenary Lecture 3

13:30-13:35 OPENING PL3

Moderator ෇߈।

14:20-15:00 AN UPDATE IN PARATHYROID DISEASE MANAGEMENT AND PATHOGENESIS

March 31, 2019

೩ඐ㠈

PL2: Plenary Lecture 2

14:15-14:20 OPENING PL2

Moderator

‫׊ݔ‬ႁ

‫ݔ‬ϧ኉

Agenda

DAROC-TADE Joint Symposium

March 30, 2019 Ȫ101 Roomȫ

2019 ഀ៊՗ᑦᆀข (CGM) ᇰᜍϏձ֬ - ପӬᑦ‫ࡿ੿׎‬Ж Time

Topic

Speaker

Moderator

08:00-08:20 ൣ‫ژ‬ ೩ඐ㠈

08:20-08:30 OPENING DAROC-TADE-1

08:30-09:20 ԄեձяΚӌಓӬሰؒՅέᆡྦᙐϾ ‫ ޠ‬CGM ൣ֚

‫ݔ‬პᘅ

೩ඐ㠈

DAROC-TADE-2

09:20-10:10 ௄ CGM ᅌϾࣽґ‫ٿ‬ѻӶᑦ‫੿׎‬ᆔ౪ ‫ِޠ‬Ք

‫ݔ‬з៤

‫ݔ‬ਣ໌

10:10-10:20 COFFEE BREAK DAROC-TADE-3

10:20-11:10 CGM ᄈ੿΢Ңࣁ࠯ᄙІᑦ‫੿׎‬ᆔ౪‫ޠ‬ ኈ៫пᖞ‫ט‬ᄃ‫پ‬ϸ‫ٵ‬

؄ਥཐ

؈ࡧ኉

DAROC-TADE-4

11:10-12:00 ᕋᎵᆔ౪Ӷ CGM ყ໦‫ِޠ‬Քᇅϸ‫ٵ‬

ചવኌ

е‫ݾ‬ϰ

15

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30, 2019 Ȫ301 Roomȫ Time

MTP-D: Meet the Professor - Diabetes Topic

Speaker

David G. MTP-D 17:00-18:00 SURGICAL MANAGEMENT OF THE DIABETIC FOOT: YOUR WOUND, ISCHEMIA Armstrong AND FOOT INFECTION (WIFI) SETTINGS

March 30, 2019 Ȫ401 Roomȫ Time

༂ऊ൞

MTP-E: Meet the Professor - Endocrine Topic

MTP-E 17:00-18:00 UPDATE IN METABOLIC BONE DISEASES SEEN BY ENDOCRINOLOGISTS

16

Moderator

Speaker

Moderator

Dolores M. Shoback

ጿջང

Agenda

March 30, 2019

SD1: Symposium-Diabetes 1

Ȫ301 Roomȫ

2019 Taiwan DM Atlas and Registry

Time

Topic

Speaker

Moderator ೩ඐ㠈

15:20-15:25 OPENING Edward J Boyko

೩ඐ㠈

SD1-2 15:55-16:25 EPIDEMIOLOGICAL PATTERNS AND CHALLENGES OF DIABETES CARE IN TAIWAN

೩‫ע‬Ԛ

ᔝ‫ݎ‬঩

SD1-3 16:25-16:55 DESIGN AND PRELIMINARY FINDINGS OF TAIWAN DIABETES REGISTRY (TDR)

‫ݔ‬ਣ໌

եᐢ೾

SD1-1 15:25-15:55 UPDATE ON DIABETES EPIDEMIOLOGY IN THE UNITED STATES

եᐢ೾

16:55-17:00 CLOSING

March 30, 2019

SD2: Symposium-Diabetes 2

Ȫ402CD Roomȫ

Diabetic Kidney Disease : An Update

Time

Topic

Speaker

Moderator ٛᓃይ

15:20-15:25 OPENING ചߝ໸

ٛᓃይ

SD2-2 15:55-16:25 MANAGEMENT OF DKD WITH OR WITHOUT CARDIOVASCULAR DISEASE

Daisuke Yabe

ചᄹᆌ

SD2-3 16:25-16:55 SELECTION AND CHOICE OF ANTIDIABETIC DRUGS IN DKD, ESPECIALLY IN MODERATE TO ADVANCED STAGE CKD

‫݁ݔ‬኉

؈ࡧ኉

SD2-1 15:25-15:55 DIABETIC KIDNEY DISEASE: UNMET ISSUES

16:55-17:00 CLOSING

؈ࡧ኉

17

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 31, 2019

SD3: Symposium-Diabetes 3

Ȫ101 Roomȫ

Prof. Gerald Reaven Memorial Symposium

Time

Topic

Speaker

08:00-08:10 OPENING ( ኈбӲ៬ )

Moderator ೩ඐ㠈

SD3-1 08:10-08:35 GLYCEMIC CONTROL AND VASCULAR COMPLICATIONS: A FOCUS ON RECENT LONG-TERM FOLLOW-UP OF GLUCOSE LOWERING TRIALS AND THE TRIUMVIRATE OF GLUCOSE MANAGEMENT

Peter Reaven

ᔝ‫ݎ‬঩

SD3-2 08:35-09:00 PHYSIOLOGY AND FRIENDSHIP

Philip S. Tsao

ᗃς݃

եᐢ೾ രहડ ‫ؖ‬኉݀ ᎓ఃྜ ೆ৩ㅉ ֕ఄ໱ ᇥ ⢿ е‫ڄ‬Н

Ida Chen

SD3-3 09:00-09:25 MEMORIAL REMARKS FROM FRIENDS, COLLEAGUES AND STUDENTS IN TAIWAN

09:25-09:30 CLOSING AND GROUP PHOTO

18

Ida Chen

Agenda

March 31, 2019

SD4: Symposium-Diabetes 4

Ȫ301 Roomȫ

DM Care in the Older People

Time

Topic

Speaker

Moderator ചᄹᆌ

08:00-08:05 OPENING Masato Odawara

ചᄹᆌ

SD4-2 08:35-09:00 OLD SOLDIERS NEVER DIE THEY JUSTɆFRAILɇAWAY---SARCOPENIA AND FRAILTY IN DIABETIC PATIENTS.

‫ݔ‬ኋឮ

ചఽֆ

SD4-3 09:00-09:25 THE EPIDEMIOLOGY AND PATHOPHYSIOLOGY OF DIABETES IN THE OLD PEOPLE

؄࠶኉

༂࡛ᄀ

SD4-1 08:05-08:35 ACCELERATING AGEING IN DIABETES IN ASIA: NEW EVIDENCE AND PERSPECTIVES OF TREATMENT IN ELDERLY T2DM

༂࡛ᄀ

09:25-09:30 CLOSING

March 31, 2019

SD5: Symposium-Diabetes 5

Ȫ402CD Roomȫ Time

Application of AI in Diabetes: From Diagnosis to Management Topic

Speaker

Moderator ྇୊ി

08:00-08:05 OPENING SD5-1 08:05-08:35 AI FOR DIABETES MANAGEMENT: THE LAST MILE OF DIGITAL HEALTH

֕ᅖത

྇୊ി

SD5-2 08:35-09:00 EARLY DETECTION OF ACUTE COMPLICATIONS IN IDDM PATIENTS USING NOVEL MULTI-BIOMARKER CGM DEVICE

༂ఽ߹

ᗃ݃ঢ়

SD5-3 09:00-09:25 DASH BOARD FOR IMPROVING DM CARE: TCVGH EXPERIENCE

‫ۤؖ‬ᓘ

ጿзᐪ

09:25-09:30 CLOSING

ጿзᐪ 19

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 31, 2019 Ȫ101 Roomȫ Time 14:45-14:55

SD6: Symposium-Diabetes 6 Prof. Ida Chen Honorary Symposium Topic

Speaker

OPENING ( ኈбӲ៬ )

Moderator ೩ඐ㠈

SD6-1 14:55-15:25 INSULIN RESISTANCE: THE GENETIC AND PHYSIOLOGIC INTER-RELATIONSHIP BETWEEN TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE; AND THE INTERFACE BETWEEN TAIWAN AND CALIFORNIA: BOTH THE LEGACY OF PROFESSOR YII-DER IDA CHEN.

Jerome Rotter

ᔝ‫ݎ‬঩

SD6-2 15:25-15:50 TRNASLATIONAL RESEARCH OF ADIPONECTIN- A TALE OF COLLABORATION

ೆҴҖ

եᐢ೾

SD6-3 15:50-16:00 MY JOURNEY OF RESEARCH FROM INSULIN SENSITIVITY TO GENETIC STUDY: LEARN FROM IDA CHEN

ࢺΛϧ

‫ؖ‬኉݀

SD6-4 16:00-16:10 CHROMOSOME 9P21 POLYMORPHISM AND CARDIOVASCULAR DISEASE

؄࠶኉

ᅫ ࢎ

Ida Chen

ೆҴҖ

᎓ఃྜ ֕ఄ໱ ೆ৩ㅉ ֕ᑠԋ ᇥ ⢿

ೆҴҖ

SD6-5 16:10-16:20 HONORARY REMARKS 16:20-16:25 ADDITIONAL HONORARY REMARKS AND GROUP PHOTO

20

Agenda

March 31, 2019

SD7: Symposium-Diabetes 7

Ȫ301 Roomȫ

DM Glucose Treatment : An Update

Time

Topic

Speaker

Moderator ጿзᐪ

14:45-14:50 OPENING SD7-1 14:50-15:30 UPDATE OF INTERNATIONAL GUIDELINES FOR DIABETES MANAGEMENT

؄҅ϰ

ጿзᐪ

SD7-2 15:30-16:10 DAROC CLINICAL PRACTICE GUIDELINES FOR DIABETES CARE - 2019 UPDATE

Ԩ‫ע‬Ꮫ

༂ऊ൞

All

؈ࡧ኉

SD7-3 16:10-16:20 PANEL DISCUSSION

؈ࡧ኉

16:20-16:25 CLOSING

March 30, 2019

SE1: Symposium-Endocrine 1

Ȫ401 Roomȫ Time

KES and ESROC Joint Symposium Topic

Speaker

Moderator

15:20-15:25 OPENING SE1-1 15:25-16:05 THYROID NODULE: CONSENSUS &CONTROVERSIES SE1-2 16:05-16:35 CONSENSUS AND CONTROVERSIES OF MANAGEMENT OF THYROID MICROCARCINOMA. SE1-3 16:35-16:55 NATURAL ORIFICE TRANSLUMINAL ENDOSCOPIC AND ROBOTIC THYROID SURGERY: THE PROMISING RESULT WITH IDEAL OUTCOMES

Hossein Gharib Young-Kee ෇߈। Eun Jig Lee Shong ച‫ي‬፲

16:55-17:00 CLOSING

21

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30, 2019

SE2: Symposium-Endocrine 2

Ȫ402AB Roomȫ

AI in New Generation of Medicine

Time

Topic

Speaker

Moderator ྇୊ി

15:20-15:25 OPENING SE2-1 15:25-15:55 ΢ϏහኌᇅᐡᏣ΢ – හኌᚃᕜ‫ึུޠ‬৥

രҴԚ

྇୊ി

SE2-2 15:55-16:25 ୾ር΢ϏහኌӶᚃᕜ‫ޠ‬ᗎ༗

؈࠶ዯ

ച‫ؙ‬໫

SE2-3 16:25-16:55 Ң‫ޑ‬ၦଊᅌᆘ‫ݳ‬Ϝ‫ޠ‬΢Ϗහኌ

ചং࿋

ച‫ؙ‬໫ ച‫ؙ‬໫

16:55-17:00 CLOSING

March 30, 2019

SE3: Symposium-Endocrine 3

Ȫ202 Roomȫ

Update of Adrenal Tumors

Time

Topic

Speaker

Moderator ചో਷

15:20-15:25

OPENING

SE3-1

15:25-15:55

DIFFERENTIAL DIAGNOSIS, INVESTIGATION AND THERAPY OF ADRENAL INCIDENTALOMAS.

ង।Н

ചో਷

SE3-2

15:55-16:25

INTERVENTIONAL RADIOLOGY OF THE ADRENAL GLANDS: CURRENT STATUS

஼ਤၗ

ചో਷

SE3-3

16:25-16:55

UPDATE OF ADRENAL TUMORS: SURGERY OF ADRENAL TUMOR

еᆉ࿘

༂Љಉ

16:55-17:00 CLOSING

22

༂Љಉ

Agenda

March 31, 2019

SE4: Symposium-Endocrine 4

Ȫ401 Roomȫ

Thyroid Disease in Pregnancy

Time

Topic

Speaker

Moderator ചࡧႁ

08:00-08:05 OPENING SE4-1 08:05-08:45 THYROID & PREGNANCY

Hossein Gharib

ചࡧႁ

SE4-2 08:45-09:10 THYROID DISEASE AND LACTATION

ࢋ๣ᇉ

ചࡧႁ

SE4-3 09:10-09:35 THE INFLUENCE OF IODINE TO PREGNANT/NEONATEɅ S THYROID

༂֘ᆃ

‫׊ݔ‬ႁ ‫׊ݔ‬ႁ

09:35-09:40 CLOSING

March 31, 2019

SE5: Symposium-Endocrine 5

Ȫ402AB Roomȫ

Update in Pituitary Disease

Time

Topic

Speaker

Moderator ဩਐᖑ

08:00-08:05 OPENING SE5-1 08:05-08:35 TREATMENT STRATEGY FOR PROLACTINOMA

Eun Jig Lee

ဩਐᖑ

TH SE5-2 08:35-09:05 THE 4 EDITION (2017) OF WHO CLASSIFICATION OF PITUITARY TUMORS

‫ݔ‬ςല

஼ኋ‫܇‬

SE5-3 09:05-09:35 RECENT EVOLUTION OF ENDOSCOPIC ENDONASAL SURGERY FOR TREATMENT OF PITUITARY ADENOMAS

྇ς҅

஼ኋ‫܇‬

09:35-09:40 CLOSING

஼ኋ‫܇‬

23

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 31, 2019

SE6: Symposium-Endocrine 6

Ȫ401 Roomȫ

Update in Osteoporosis

Time 14:45-14:50

Topic

Speaker

Moderator ጿջང

OPENING

SE6-1 14:50-15:20

RECENT UPDATE IN BASIC SCIENCE OF OSTEOPOROSIS

ߚ୊ઊ

ጿջང

SE6-2 15:20-15:50

UPDATE IN EPIDEMIOLOGY AND DIAGNOSIS OF OSTEOPOROSIS

༂ӑύ

ጿջང

SE6-3 15:50-16:20

RECENT ADVANCES IN PHARMACEUTICAL TREATMENT OF OSTEOPOROSIS

ጿջང

؄߫቉

16:20-16:25

March 31, 2019 Ȫ402AB Roomȫ

؄߫቉

CLOSING

SE7: Symposium-Endocrine 7 Radiofrequency Ablation in Endocrine Disease: Thyroid and Others

Time

Topic

Speaker

Moderator е‫ڄ‬Н

14:45-14:50 OPENING SE7-1 14:50-15:30 THYROID RADIOFREQUENCY ABLATION: Jung Hwan PAST PRESENT AND FUTURE Baek

е‫ڄ‬Н

SE7-2 15:30-16:00 RFA IN THYROID DISEASES: THE VIEW OF ENDOCRINOLOGIST IN TAIWAN

е‫ݾ‬ϰ

е‫ڄ‬Н

SE7-3 16:00-16:30 THE DEVELOPMENT OF RFA OF THYROID DISEASE: TECHNIQUE AND PATENT IN TAIWAN

ᗃ࿳߭

஼Љ໚

16:30-16:35 CLOSING 24

஼Љ໚

Agenda

March 31, 2019 Ȫ402CD Roomȫ

YL: Basic Research and Young Investigator Research Lecture

Time

Topic

Speaker

Moderator ೆ৩ㅉ

14:45-14:50 OPENING YL-1

14:50-15:20 HEME-DERIVED BILINS: NEW THERAPEUTICS FOR INFLAMMATORY DISEASES

Jon Y. Takemoto

ೆ৩ㅉ

YL-2

15:20-15:50 INVESTIGATION OF THE CAUSES AND MANAGEMENT OF NON-ALCOHOLIC FATTY LIVER DISEASES

ᒄᘺৡ

༂࡛ᄀ

YL-3

15:50-16:05 INVESTIGATING THE ROLE OF GLUCOCORTICOID-HEPASSOCIN PATHWAY IN THE HIGH-FAT DIETINDUCED OBESITY-RELATED METABOLIC DISORDERS

106 Ԓ Research Grant ࢺ㦬ᄕ

྇୊ി

YL-4

16:05-16:20 THE RELATIONSHIP BETWEEN SERUM ANGPTL6 AND INCIDENT DIABETES IN HUMAN – FOLLOW UP STUDY

106 Ԓ Research Grant ؄҅ϰ

ٛᓃይ

16:20-16:25 CLOSING

ٛᓃይ

25

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30-31, 2019

LS: Lunch Symposium Room 402AB

Room 402CD

220 ΢

200 ΢

200 ΢

Room 101 Room 301 Room 401 600 ΢ March 30 12:00-13:00 March 31 12:10-13:10

March 30, 2019

220 ΢

Room 202 Room 203 80 ΢

80 ΢

LS1

LS2

LS3

LS4

LS5

LS6

LS7

Լ᡺‫ٺ‬

ᓷؔ‫ݎ‬

ᒜ‫ڸ‬ᒜ኉

Ѕ๽

जՕւᅮ

ߢල੬௧ւஷ

ᎄ࿆

LS8

LS9

LS10

LS11

LS12

LS13

ᒜ๽

ᗊᒜຆ

ᒜ‫ڸ‬ᒜ኉

഻ઊ

जા٩Ѽ

ᙅ‫ٿ‬

Topic

Speaker

Moderator

LS1

Լ᡺‫ٺ‬

NEW EVIDENCES AND INDIVIDUALIZED THERAPY OF DPP4I AND SGLT2I

Daisuke Yabe

؈ࡧ኉

LS2

ᓷؔ‫ݎ‬

T2DM MANAGEMENT STRATEGIES IN YOUNG POPULATION AND ELDERLY POPULATION

Hirotada Watada

‫ݔ‬ਣ໌

྇ۤ⧣

༂࡛ᄀ

Ԩ‫ע‬Ꮫ

ചᄹᆌ

஼Ϡδ

֕ਤಉ

CLINICAL IMPLICATIONS OF ALERE AFINION IN THE CARE OF DIABETES PATIENTS

ι‫܉‬л

֕ਤಉ

DEBATE: SHOULD DPP-4 INHIBITOR REMAIN THE MAJOR CHOICE IN T2DM PATIENTS, WHILE MORE EVIDENCES COMING FROM SGLT-2 INHIBITOR? YES – DPP-4 INHIBITORSɅ EFFICACY, SAFETY, AND EXPERIENCES

‫ݔ‬ኋឮ

೩ඐ㠈

NO – CHANGE SHOULD BE CONSIDER FOR MORE

ዊ҅ው

೩ඐ㠈

WHERE DO WE STAND IN DIABETIC DYSLIPIDEMIA: EVIDENCE, GAP, AND FUTURE OF LIPID MANAGEMENT

؄जУ

ೆҴҖ

AN INSIGHT INTO THE OPTIMAL DPNP DIAGNOSIS AND TREATMENT MODEL

஼ࡲ֘

ೆҴҖ

LS3

ᒜ‫ڸ‬ᒜ኉ PILOT EXPERIENCE OF INSULIN THERAPY

WITH NOVEL BASAL INSULIN

LS4 LS5

Ѕ๽

REVEAL THE MASK OF STATIN-INDUCED NEWONSET DIABETES MELLITUS

जՕւᅮ ACCURATE AND RAPID MEASUREMENT OF

GLYCATED HAEMOGLOBIN USING ALERE AFINION

LS6

LS7

26

ߢල੬ ௧ւஷ

ᎄ࿆

Agenda

April 9, 2017 LS8

ᒜ๽

LS9

ᗊᒜຆ

Topic TAILORING TREATMENT STRATEGIES IN S NEW ?

ELDERLY DIABETES : WHATɅ OPTIMIZING THE SAFETY-EFFICACY EQUATION IN T2D PATIENTS USING INSULIN AS A FOUNDATIONAL AGENT

LS10 ᒜ‫ڸ‬ᒜ኉ NEW ADA/EASD CONSENSUS GUIDELINES FOR T2D HIGHLIGHT GLP-1 RA THERAPY LS11

഻ઊ

THE NEWLY RELEASED CAMELLIA-TIMI 61---THE CV OUTCOME TRIAL OF 5HT-2C AGONIST

LS12 जા٩Ѽ NEBIVOLOL, A NEW FAVORABLE THERAPEUTIC OPTION FOR THE TREATMENT OF TAIWAN DIABETIC HYPERTENSIVE PATIENTS : FROM THE LATEST GUIDELINE TO REAL WORLD ASIAN EXPERIENCE LS13

ᙅ‫ٿ‬

NEW ROLE OF GLP-1 RAS IN CLINICAL PRACTICE FOR T2DM; FROM RCT TO RWE

Speaker

Moderator

Masato Odawara

ऩఃҖ

ҥസϧ

؄जУ

֕‫܇‬ᐆ

ᇥ ⢿

྇݁ᅡ

ചᄹᆌ

Athanasios J. Manolis

؈ࡧ኉

е‫ݾ‬ϰ

༂࡛ᄀ

27

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30 2019 Ȫ402CD Roomȫ ਣȁ໣

OD: Oral Presentation- Diabetes ൣ֚ձ޲

лࡼ΢

OD-1 17:00-17:10 ಒΡ࠯ᑦ‫੿׎‬Ӭ‫ڂ‬ಒή෉ᄛ‫ܓ‬๬᠛૿ᆒ ϟԬκᇅ๬᠛ѓ૗૿ଞॴᓏӱφ

ചӍ๸

ᗃ݃ঢ়

OD-2 17:10-17:20 ՗ఽਰᑦਰሗ㢵 L ձ࣐ಒΚѺ෉Ң‫ࡿޑ‬ ዀׂܼ৓ᑦ‫ޠ੿׎‬ᜱᖓᇅႲข

еឋᎪ

ᗃ݃ঢ়

OD-3 17:20-17:30 ାᓝѵഌՋՉ‫ڗ‬ᐮᄈಒ 2 ࠯ᑦ‫੿׎‬Ӽึ ‫ܓ‬ઢစ੿ᡑொ޲ϟਞઊ

ࢺΛϧ

ചఽֆ

OD-4 17:30-17:40 ңᐡᏣᏱಭРԓႲขᑦ‫੿׎‬՟ଲ੿΢ߞ ෉Ԭκ౦

؄ԈⰩ

ചఽֆ

OD-5 17:40-17:50 ҂ְᑦϾ՗Քષᄈಒ 2 ࠯ᑦ‫੿׎‬΢՗ᑦ ᡑ౵࡚ᇅӓӱԬκ౦ࣻᜱ‫ޠܓ‬ኈ៫

ചఽֆ

ࢺΛϧ

OD-6 17:50-18:00 хᗃ઀߯ထ੿΢ജႬ‫ ܓ‬LDL စҦ།ড় STRA6-Retinol ৸ၰЖକл୞૖๕‫ޒ‬฾Ͼ

ٛᓃይ

ࢺΛϧ

March 30 2019 Ȫ402AB Roomȫ ਣȁ໣

ᚡȁҭ

OE: Oral Presentation- Endocrine ᚡȁҭ

ൣ֚ձ޲

лࡼ΢

OE-1

17:00-17:10 I-131 NP-59 ӏφആኈ೛Ӷ঩ึ‫ܓ‬Ӽㄶ ⢅઀‫ޠ‬ຩᘟቌঅȈѯᢋіഌ࢛ᚃᏱϜЗ ‫ޠ‬Ӳ྘‫ܓ‬ः‫ف‬

֕݃⼻

ᙐም‫ع‬

OE-2

17:10-17:20 ҧ‫ޒ‬သϦໍ‫ڸ‬ం՗઀՟ଲࣻᜱ‫ܓ‬

஼ҴЗ

ᙐም‫ع‬

OE-3

17:20-17:30 ҧ‫ޒ‬သϦໍЖକ‫ن‬ѓ૗౵ள‫ޠ‬Ⴒขӱφ

ᗃᓘᇉ

е‫ݾ‬ϰ

OE-4

17:30-17:40 ໱‫ܓ‬ೊᅮᇍ௦‫ڨ‬ᡞӶϛӤ‫ܓ‬րҧ‫ޒ‬သ‫ٱ‬ ऐᕝ੿΢‫ߓޠ‬౫ᇅလድึҢԥᜱ

‫ڻ‬ਐസ

е‫ݾ‬ϰ

OE- 5 17:40-17:50 Җ୾ 107 ԒіѯᢋഎཽୣϟѺஐ࿩ᕋᎵ ።ࢦ

༂֘ᆃ

ቔቄ࣏

഍ᓇ‫ݙ‬

ቔቄ࣏

OE-6 28

17:50-18:00 ՗ዏဋඳ೛‫ݾ‬ᕜҧ‫ޒ‬သॴኹ

Agenda

March 30-31, 2019 Ȫήዃٗඃȫ

AP: 2019 Award ᚡȁҭ

ձ ޲

ലяः‫ف‬ዪ AP-1 THE DIVERSIFIED ROLE OF LIVER FAT AND HEPATOKINES IN METABOLIC DISEASES

ዊ҅ው

ᒜ๽ᓻ‫ؿ‬፤Нዪ AP-2 GENETIC VARIATION OF SORBS1 GENE IS ASSOCAITED WITH GLUCOSE HOMEOSTASIS AND AGE AT ONSET OF DIABETES: A SAPPHIRe COHORT STUDY

஼ࡲ֘

ᒜ‫ڸ‬ᒜ኉ᓻ‫ؿ‬፤Нዪ AP-3 TRANSCRIPTOME ANALYSIS OF PAPILLARY THYROID CANCER HARBORING TELEMERASE REVERSE TRANSCRIPTASE PROMOTER MUTATION

ᙐም‫ع‬

29

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30-31, 2019

PD: Poster Presentation-Diabetes лࡼ΢Ȉ‫ݔ‬ਣ໌ȃе߹ᑺȃ؄࡛ᑺ ຠϸਣ໣ȈMarch 31 , 2019 09:30-09:45 ( ήዃٗඃ ) ᚡȁҭ

ಒΚձ޲

PD1

௦‫ڨ‬ஆᙄ૏৭ષ‫ܗ‬Ⴒె࠯૏৭ષ‫ޠ‬ಒΡ࠯ᑦ‫੿׎‬ொ‫ޠ‬՗ᑦ‫ݱ‬୞ᇅᓜ୞ ૖ϲጱࠕ࡚ϟ໣‫ࣻޠ‬ᜱ‫ܓ‬

еঢ়߈

PD2

ђΤᑦ‫੿׎‬ӔӤྲៗᆪԥֆܼ‫׾‬๢੿΢‫ޠ‬ነ᢯І՗ᑦ௢‫ښ‬

ጿ‫࣢ڄ‬

PD3

пᑦ‫ߓ࣐੿׎‬౫ϟ՗Քષ‫ؗ‬຀઀ : ঐ਱ൣ֚

‫࠽يݔ‬

PD4

ᡑ౵՗ՔષᄈᑦϾ՗Քષข໕‫ޠ‬ኈ៫ – ੿‫پ‬ൣ֚

‫߹ݔ‬Ӈ

PD5

ᇅᎥᢅᐩ࡚αЁࣻᜱ‫ޠ‬ᑦ‫੿׎‬⢅ሗϜࢴ - ঐ਱ൣ֚

‫ݔ‬φអ

PD6

MIR302 ഇႇࣁϾ૏৭ષଊਁ༉ሏၰ৸෶ጦᑦ૎ࢴ‫ܓ‬ᇷึ‫ޠ‬૏৭ ̀ ಡबѓ૗ሬᛥ‫ڸ‬ডκ

؄‫ݡ‬ᐖ

PD7

Ӷ C2C12 ՋᆔϜ LIRAGLUTIDE ෶ጦ෭ᚕ૎޻ሗᇷᏳ‫ޠ‬૎ࢴ‫ڸܓ‬૏ ৭ષߣ‫׫‬

؄‫ݡ‬ᐖ

PD8

GLP-1 ‫ڨ‬ᡞߵਞᏙ෶ጦା૎໾ॶЖକϟઢစ‫ވึܓ‬Іฑኍ՘࣐

ߚឡዬ

PD9

‫׎‬ሗᇅಒΡ࠯ᑦ‫੿׎‬ொ೗Ҫ‫ึ׎‬ҢॴᓏȈΚঐ 4.5 Ԓ‫ޠ‬зхः‫ف‬

ᒧ᜸Ԅ

PD10

TYROSINE-KINASE-INHIBITOR ЖึϟՍᡞռ࣬ᑦ‫੿׎‬

༂࡞ᓓ

PD11

пӓѵᡘφԪзхۢ‫ٿז‬ጃᇰ‫ڎ‬ঐԒሇ΢ϟԚዤ෉ึ੿࠯ᑦ‫ޠ੿׎‬ᇄ ᢋ΢ঢ়ఋϟय੿ஆӱ

ച

PD12

ຠզ૏৭ષድ‫ٻ‬ң OCTREOTIDE ІК೛ϹଷӬ‫ץڂ‬ഁ૏৭ષᆀขӶ ՗ᑦα‫ޠ‬ኈ៫Ȉ ੿‫پ‬ൣ֚

༂Ԅ‫ٿ‬

PD13

‫؂‬τմஞ࡚ᖛ‫ڿ‬᎖ᡑ౵‫ܓ‬ቩђಒΡ࠯ᑦ‫੿੿׎‬΢‫ޠ‬З՗ᆔ‫ٲ‬ӈ‫ॴޠ‬ᓏ

৹❒ᔆ

PD14

௥ଇᑦ‫੿෉ࠊ੿׎‬΢ϟ՗షᑦϾҪ೗ҪȃᑦϾ՗Քષᐩ࡚ᇅᑦ‫੿׎‬ຝ ᆪጱ੿ᡑ‫ࣻޠ‬ᜱ‫ܓ‬

ᒧპጝ

30

ၾ

Agenda

ᚡȁҭ

ಒΚձ޲

PD15

ಒΚ࠯ϲҫષᙥҦӼ२‫ޠ‬ᐮ㢵ଊਁഋ৸‫ڗ‬ᐮࠊ૎޻ಡब‫ޠ‬Ңߞ

ᒄԋా

PD16

७՗ᑦ᛿‫ޑ‬Ӷᑗ྄௢ᇨᑦ‫੿׎‬З՗ᆔ‫ٲ‬ӈϜ‫׹ܛ‬ᅌ‫ِޠ‬Ք

ྤጝঘ

PD17

ѯᢋߗΫԒ໣‫ٻ‬ң७՗ᑦ᛿‫ޑ‬ᇅାմ՗ᑦ‫ٲ‬ӈ‫ޠ‬ᗎ༗ᡑϾ

༂ਫࡰ

PD18

SGLT2 ‫ښ׼‬Ꮩ૗စҦຝ༂᎖ଊਁ༉ሏၰ৸ߴៗᑦ‫̀ ੿׎‬-CELLS

ചᆻ໥

PD19

ಒ 2 ࠯ᑦ‫੿׎‬Ӭ‫ڂ‬ᄛ‫ܓ‬๬੿ಒ 3-4 ෉ொ޲‫ ޠ‬HBA1C ᡑ౵‫ܓ‬ᇅ๬᠛੿ ໍ৥‫ޠ‬ᜱᖓ‫ܓ‬

೩Ξᖩ

PD20

Щၷп TOUJEO ‫ ܗ‬LEVEMIR ձஆᙄ૏৭ષӶ՟ଲߩ੿ӡ՗ᑦ௢‫ښ‬ ϛًᑦ‫੿׎‬ொ՗ᑦ௢‫ښ‬ᕜਞ - Κୣ஀ఁᏱᚃଲ‫ޠ‬စᡜ

؄࿆ಉ

PD21

ຠզ᜹Ёᑦષ㣖 -1 ‫ڨ‬ᡞߵਞᏙ (GLP-1 RA, Ԅ LIRAGLUTIDE) Ӭ‫ڂ‬ஆᙄ૏৭ષ (BASAL INSULIN) ܼႲె࠯૏৭ષ (PRE-MIXED INSULIN, єࢃ NOVOMIX ‫ܗ‬ ࢑ HUMALOG MIX) ‫ݾ‬ᕜկ௢‫ښ‬ϛ‫ޠٺ‬ಒΡ࠯ᑦ‫੿׎‬ϟᖞ‫ט‬ਞ‫ݏ‬ᇅԋӓ‫ܓ‬

ቔහଗ

PD22

LIRAGLUTIDE ೾ႇ AMP ᐮࣁ‫ޠ‬೗Ҫᐮ㢵‫ٸ‬ᒧ‫ܓ‬ᐡ‫ ښ׼ښ‬C ࠯‫ࢴ੿ވن‬ፓᇨ

؄जУ

PD23

૏৭ષ‫ৣݨ‬ႇ໕ș਱‫پ‬ൣ֚

ዟ໌Җ

PD24

ାዶષᄈဝഌҫίဝ૎޻Щ౦‫ޠ‬ᡑϾཽ७մစҦᡞ२෶२ॏฬࡤѯᢋ޴ण‫ܓع‬ ‫ޠ‬хᗃ઀঑ထϟॴᓏ

ᄒ߹Ҕ

PD25

DPP4 ‫ښ׼‬ᏙѠп෶Ўѯᢋӵୣᑦ‫੿׎‬΢‫ޠ‬ႇఄ‫ܓ‬ቆ‫ވ‬

ച߭‫׊‬

PD26

ౢኹ‫ܓ‬ಒ 1 ࠯ᑦ‫੿׎‬ϟ਱‫پ‬ϸ‫ٵ‬

༂ࠓᇻ

31

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30-31, 2019

PE: Poster Presentation- Endocrine лࡼ΢Ȉងีྶȃߚ୊ઊȃ֕ஏᆋ ຠϸਣ໣ȈMarch 31 , 2019 09:30-09:45 ( ήዃٗඃ ) ᚡȁҭ

ಒΚձ޲

PE1

ቋ฾΢઀঑ထ -- Սᡞռ࣬Ӽ२ϲϸ‫઀ݫ‬঑ထಒΡ࠯

ဩजԚ

PE2

੿‫پ‬ൣ֚Ȉ‫׫‬ҧ‫ޒ‬သ᛿‫ึڂޑ‬ᗼಗ‫ܓ‬Ҫ՗౩ુн઀

‫࡞ݔ‬Ԉ

PE3

ҧ‫ޒ‬သᐮષ‫ڂ઀ܓ׫‬ဟί࠮ᡞᗼಗಡबድ ( ਱‫پ‬ൣ֚ )

‫ݔ‬Ҟ‫ܒ‬

PE4

૔သτಡबઢစϲϸ‫ݫ‬ᕝӱକ ECTOPIC ACTH ϸ‫઀ݫ‬঑ထ ( ਱‫پ‬ൣ֚ )

‫ݔ‬Ҟ‫ܒ‬

PE5

৳‫ݡ‬Ы઀୞ᄙѓ૗ᔯࢦ‫ޠ‬ЇளЇᔗȈΚঐѽτ߮᠜‫ߵܓ‬๬αသҫ፵ᐮ ષಡबድ‫ޠ‬਱‫پ‬ൣ֚

‫ݔ‬ଗᆱ

PE6

੿‫پ‬ൣ֚ : ৳‫ݡ‬Ы઀੿ொ‫ޠ‬ଽ፵౶ᚭ઀

‫࣢يݔ‬

PE7

Κ՞঩ึ‫ܓ‬ҧ‫ޒ‬သѓ૗մίϟυ‫ܓ‬пᡫに࣐ߓ౫ϟঐ਱ൣ֚

؄࿆ಉ

PE8

ҧ‫ޒ‬သॴኹ‫ٻ‬ңဩջጱМࡼ ੿‫پ‬ൣ֚

еུ❒

PE9

ါ࿆Њ૮੿௦‫ڨ‬൑ΚᏙ໕ܺৣ࿩‫ݾ‬ᕜ‫ޠ‬ԚਞІኈ៫Ԛ‫ݏ‬ϟӱφ

྇໌߫

PE10

NIVOLUMAB ‫ܛ‬Ᏻय‫ޠ‬ҧ‫ޒ‬သ‫پ੿ – ވ‬ൣ֚

еՎᆋ

PE11

LENVATINIB ңܼܺৣ࿩‫ݾ‬ᕜႳ‫ܓڿ‬ϸϾ࠯ҧ‫ޒ‬သᕝӒࠊ‫ݾ‬ᕜѷਞࡤ ϟ཮ఀ‫ݾܓ‬ᕜ

ᒢᘅሊ

PE12

‫ܓࡩٴ‬ҧ‫ޒ‬သ‫ވ‬Ӭ‫ڂ‬୚ҧ‫ޒ‬သѓ૗մί઀ - ੿‫پ‬ൣ֚

༂ਫဥ

PE13

ᑣ‫ ޒ‬- ਻⛔‫࠯ޒ‬ҧ‫ޒ‬သ‫ٱ‬ऐᕝಣᙒ‫࠯ٴ‬Ȉ਱‫پ‬ൣ֚ІНᝧӲ៬

ചҘԒ

PE14

ࠓѯᢋҧ‫ޒ‬သᕝ੿ொ‫ึڂ‬ಒΡ঩ึᕝϟӲ྘‫ܓ‬ः‫ف‬

֕ਫ൪

PE15

ဟί࠮ᡞߵҧ‫ޒ‬သષသድӶ‫ݔ‬πߞ۹ᚃଲ‫ޠ‬ᖞ‫ט‬စᡜ

֗ྕृ

PE16

ҧ‫ޒ‬သ‫ٱ‬ऐᕝึҢӶѢ୐ᚈଽαୣ‫ޠ‬౵՞‫ܓ‬ҧ‫ޒ‬သಣᙒ

ചዬඐ

32

Agenda

ᚡȁҭ

ಒΚձ޲

PE17

ৣᓝ੒ᒋ೛ңܼ‫ݾ‬ᕜ‫׌‬ഌඉึ‫ܓ‬ҧ‫ޒ‬သ‫ٱ‬ऐᕝӬ‫ిڂ‬Вᙾಌ - ੿‫پ‬ൣ ֚ІНᝧӲ៬

ച‫ޙ‬ዔ

PE18

౵՞‫ܓ‬୚ҧ‫ޒ‬သသድȈঐ਱ൣ֚

஼

PE19

ᢏᄇቋ฾ᆤӬ઀‫ڐڸ‬ᡑ౵࠯ȈGAD Սᡞ‫׫‬ᡞᇅՍᡞռ࣬੾੿‫ࣻޠ‬ᜱᖓ

؄ۤᒊ

PE20

਱‫پ‬ൣ֚ : ߩѓ૗‫ܓ‬૏သઢစϲϸ‫ݫ‬လድᙾϾ࣐ѓ૗‫ܓ‬૏သઢစϲϸ ‫ݫ‬လድȞඍ‫ܓ‬૏৭ષድ ) ܼ൑ΚᚃᏱϜЗ‫ ޠ‬3 ঐ਱‫پ‬Ȅ

ዟ➬߀

PE21

ҧ‫ޒ‬သϦໍ੿ொစ‫ޣ‬ဘ๞ϡ‫׫‬ҧ‫ޒ‬သ᛿‫ ޑ‬PROPYLTHIOURACIL

৹౿٥

PE22

ӶΚঐѺஐӤਣ֖౫ᑦ‫੿׎‬⢅ሗϜࢴ‫ڸ‬ҧ‫ޒ‬သࢴ઀ - ੿‫پ‬ൣ֚

᎓ᑩጹ

PE23

ϲҢ‫ܓ‬৳‫ݡ‬Ы઀঑ထ‫ུޠ‬ᑣᔯРԓȈఽఒմᏙ໕ DEXAMETHASONE ‫ܓښ׼‬ᔯᡜ

ုҰ࠳

PE24

TYOSINE KINASE INHIBITORS ᇅ MTOR INHIBITORS ‫ܛ‬Ᏻयϟϲ ϸ‫੿੾ݫ‬਱‫پ‬ൣ֚

ചఽֆ

PE25

ҧ‫ޒ‬သಡଭए‫ࡤڗ‬ആԚҧ‫ޒ‬သ‫ڸވ‬ҧ‫ޒ‬သ๗࿾ϲя՗‫پ੿ޠ‬ൣ֚

෇ᝋᓹ

PE26

ѓ૗‫ܓ‬༟ሗಡब᜹๬αသҫ፵ᕝঐ਱ൣ֚

ചၒੵ

PE27

঩ึ‫ܓ‬୚ҧ‫ޒ‬သႇାӬ‫ڂ‬ᆱҢષ D ϛ٘ঐ਱

෭ኌۤ

PE28

৳‫ݡ‬Ы઀Ȉп޳੄༭࣐ߒۗᖞ‫ߓט‬౫

஼Ղዔ

PE29

ҧ‫ޒ‬သࡩ઀ဩջጱစᡜ

‫ోࡧݔ‬

PE30

ঐ਱ൣ֚Ȉ‫ٻ‬ңᎥᢅᏳयϟҧ‫ޒ‬သᐡ૗Ϧໍ

྇ਤԏ

PE31

ҧ‫ޒ‬သ‫ٱ‬ऐᕝ‫ڂ‬ԥҫጴᙾಌလድ - ঐ਱ൣ֚

؈ߨ࣢

PE32

78 ྒυ‫ܓ‬ҧ‫ޒ‬သѓ૗մίӬ‫ڂ‬ᘈషЬလ݅ଝ

ቔᐹ߈

PE33

౵՞‫ܓ‬ҧ‫ޒ‬သ‫ٱ‬ऐᕝܼါ࿆Њ૮੿ொ޲ϟ੿‫پ‬ൣ֚

ചఽֆ

PE34

ѽτ֋லҧ‫ޒ‬သድ੾ொկณӉեҧ‫ޒ‬သ౵ளึ౫ϟ਱‫پ‬ϸ‫ݚ‬ᇅНᝧ௥ଇ

ߚ႐వ

PE35

‫ش‬ೄ՚‫ٴ‬Ы઀঑ထӬ‫׎ڂ‬஬઀਱‫پ‬ൣ֚

֕߹Ꭳ

ല

33

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 30-31, 2019 Ȫήዃٗඃȫ

BP 1-5 ኆ୧፤НᏪൣ৥ұ ᚡȁҭ

‫׺‬ጉ൑՞

BP-01

DULAGLUTIDE ‫ݾ‬ᕜࠊࡤޫဝ‫ڸ‬໼ࡤ՗ᑦᄈᑦϾ՗Քષ‫ޠ‬ଔᝧ࡚

ѯᢋᙅ‫ٿ‬

BP-02

ಒΡ࠯ᑦ‫ޠ੿׎‬๽΢‫ٻ‬ң DULAGLUTIDE ࡤึҢ‫ޠ‬ဘदၿϛً‫ٲ‬ӈ ੬ᘉ‫ޠ‬ຠզ

ѯᢋᙅ‫ٿ‬

BP-03

ѯᢋᑦ‫੿׎‬ொ޲ STATINS ‫ݾ‬ᕜ‫ٸ‬௄‫ܓ‬ᇅႲขӱφϸ‫ݚ‬

ᎄ࿆τ᛿ኆ

BP-04

STATINS ‫ٸ‬௄‫ܓ‬ᄈܼѯᢋᑦ‫੿׎‬ொ޲୞૖฾ϾЗ՗ᆔ੾੿ϟኈ៫

ᎄ࿆τ᛿ኆ

BP-05

BASELINE CHARACTERISTICS IN TAIWAN IN THE VERIFY STUDY ș A RANDOMISED TRIAL ASSESSING THE DURABILITY OF GLYCAEMIC CONTROL WITH EARLY VILDAGLIPTIN-METFORMIN COMBINATION IN NEWLY DIAGNOSED TYPE 2 DIABETES

34

ѯᢋᒜ๽

Abstract

PL-1

GENETIC DETERMINANTS OF CARDIOMETABOLIC DISEASE PHILIP S. TSAO, PH.D. Professor of Medicine (Cardiovascular Medicine); Stanford University School of Medicine Associate Chief of Staff for Precision Medicine; VA Palo Alto Health Care System Director; VA Palo Alto Epidemiology Research and Information Center (ERIC) for Genomics Co-Principal Investigator; Million Veteran Program

While obesity, type 2 diabetes (T2D) and dyslipidemia are known heritable risk factors for cardiovascular disease, it has only been recently that breakthroughs in measuring genetic variability DV ZHOO DV GHYHORSPHQWV LQ LQIRUPDWLRQ VFLHQFHV KDYH OHG WR WKH LGHQWL¿FDWLRQ RI PDQ\ JHQHWLF ORFL associated with different traits. For many of these loci, the causal variants and the mechanisms of KRZ WKH\ LPSDFW GLVHDVH UHPDLQ XQNQRZQ OLPLWLQJ WKH FXUUHQW WUDQVODWLRQDO YDOXH RI WKHVH ¿QGLQJV ,Q WKLV WDON , ZLOO GLVFXVV WKH EDVLFV RI JHQRPH ZLGH DVVRFLDWLRQ VWXGLHV DQG UHFHQW ¿QGLQJV UHODWHG WR cardiometabolic disease from the largest US-based genetic cohort, the Million Veteran Program.

35

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PL-2

AN UPDATE IN PARATHYROID DISEASE MANAGEMENT AND PATHOGENESIS DOLORES M. SHOBACK, M.D. Professor of Medicine in Residence University of California, San Francisco

Considerable progress has been made in understanding the pathogenesis and management of states of hyperparathyroidism and hypoparathyroidism that impacts the current practice of endocrinology. Primary hyperparathyroidism (PHPT) is most commonly due to a solitary adenoma (~80%) in adults with the disorder, with the remainder due to multigland hyperplasia (15-20%) or to parathyroid cancer (< 1% of cases). In more and more countries, including those in Asia, patients with PHPT present more frequently in an asymptomatic manner. In the past decades, patients presented predominantly with symptomatic disease (bone pain, fractures, renal stones, and gastrointestinal and psychiatric manifestations). Their tumors were larger, and urgent surgery was needed to effect a cure.

More commonly today, asymptomatic PHPT comes to medical attention after patients with low bone mass or fractures are evaluated biochemically, and they are essentially being screened for the disease.

Cohorts of patients with sporadic PHPT are composed mainly of postmenopausal women. Hereditary forms of the disease are more prevalent in younger patients with PHPT (age < 40-45). The following genetic conditions must be carefully considered in all patients with PHPT, but especially in younger ones, so that an accurate diagnosis is made: multiple endocrine neoplasia (MEN) 1, 2a and 4; the HPTMDZ WXPRU +37 -7 V\QGURPH GXH WR PXWDWLRQV LQ WKH JHQH HQFRGLQJ SDUD¿EURPLQ DQG GLVRUGHUV of the extracellular calcium-sensing receptor (CaSR) signaling pathway [familial hypocalciuric hypercalcemia (FHH) types 1, 2, and 3]. The clinical and biochemical features of PHPT due to these genetic conditions will be reviewed as well as the diagnostic testing that is needed to support the diagnosis of PHPT, especially in its asymptomatic form. Guidelines for the management of PHPT have been established by the 4th International Workshop on PHPT(2014) and will be reviewed.

Newer more sensitive localization techniques have developed that can be applied to the evaluation of patients for minimally invasive parathyroidectomy. Minimally invasive surgery can be combined with intraoperative parathyroid hormone (PTH) monitoring to ensure correction of the hyperparathyroid state. In cases of recurrent PHPT or in especially symptomatic patients, for whom surgery is indicated and appropriate, choline/PET-MRI scanning and 4-D computed tomography have emerged as superior ORFDOL]DWLRQ WHFKQLTXHV WKDW KDYH LPSURYHG VSHFL¿FLW\ DQG VHQVLWLYLW\ FRPSDUHG ZLWK XOWUDVRXQGV DQG sestamibi scanning. Results of studies establishing this approach and, in addition, newer trials looking DW WKH XVH RI WKH RUDO FDOFLPLPHWLF FLQDFDOFHW ZLOO EH UHYLHZHG IRU HI¿FDF\ LQ WKH ELRFKHPLFDO FRQWURO of the disease abnormalities in patients indicated for surgery who are unable to undergo it.

In a similar manner, there has been considerable progress in understanding the effects of a 36

Abstract

lack of PTH on bone, kidney and quality of life in patients. Although this disorder is rare, it is a not infrequent complication of thyroidectomy done for cancer or goiter, with about 75% of cases of hypoparathyroidism in adults being post-surgical and the remaining 25% being of genetic or other etiologies. Over the last 5-10 years, data have emerged that PTH replacement therapy may be an excellent option for patients with hypoparathyroidism whose disease is not well-controlled on standard therapy with calcium supplements and activated vitamin D analogues (calcitriol or 1-alpha calcidol) or vitamin D2 or D3. Trials have shown reductions in both calcium and vitamin D analogue intake, stabilization of disease-relevant biochemical endpoints, and improved quality of life in certain domains with initiation of PTH(1-84) therapy. Long-term outcomes of ongoing PTH(1-84) therapy are being reported, and additional approaches engineering PTH(1-34) into slowly released forms are being readied for testing in this patient population. Of special interest will be the effects of chronic PTH replacement on skeletal endpoints including bone mass, turnover, and fractures to ensure ongoing safe hormonal replacement.

Thus, considerable progress has ensued relevant to the management of states of both PTH K\SHUVHFUHWLRQ DQG 37+ GH¿FLHQF\

37

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PL-3

DIABETIC FOOT: THE GLOBAL STATE OF PLAY DAVID G. ARMSTRONG, DPM, M.D., PH.D. Professor of Surgery, Keck School of Medicine USC; Department of Surgery

Foot wounds are now the most common diabetes-related cause of hospitalization and are a frequent precursor to amputation. Persons with diabetes have a 30-fold higher life-time risk of undergoing a lower extremity amputation compared to those without diabetes. An infected foot wound precedes about two-thirds of lower extremity amputations. and infection is surpassed only by gangrene as an indication for diabetic lower extremity amputation. Persons with diabetes have at least a 10 fold greater risk of being hospitalized for soft tissue and bone infections of the foot than persons without diabetes.

With these data as a backdrop, we will review the current state of play regarding treatment of the diabetic foot and wounds in the developed and developing world. We will explore policy factors associated with the team approach to amputation prevention as well as tips for the structure of successful teams, both at SALSA and worldwide. The concept of the “Toe and Flow” philosophy of SUHYHQWLRQ ZLOO EH H[SORUHG 6XEVHTXHQWO\ HPSKDVLV ZLOO EH SODFHG RQ VSHFL¿F VXFFHVVHV DQG IDLOXUHV and perhaps a way forward toward extending ulcer-free-days in remission. We also explore the use of novel new technology merging consumer electronics with medical devices in an effort to prevent problems before they start. Further information regarding this lecture including video, manuscripts and blog available at: www.diabeticfootonline.com

38

Abstract

PL-4

HISTORY OF ENDOCRINOLOGY--THE NOBEL LAUREATES HONG DA LIN, M.D Active Emeritus, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital; Clinical Professor, Department of Medicine, Taipei Medical University Visiting Professor, Endocrine Division, Shin Kong Medical Center Hospital

Evidences of endocrine disorders and treatment exist in the ancient Chinese, Egyptians, Hindus, Biblical, Greek, Roman and other cultural antiquity. Goiters were known in China in the era of 1600BC. People used burnt sponge and seaweed in the form of powder, pills or dissolved in wine for the treatment of this disorder. “Diabetes mellitus” had already studied by Chang Chung-Ching (160219 AD), the Chinese Hippocrates. The effects of castration and infertility were well known. Eunuchs played an important role at the Court, for the service of emperors and their queens. The use of fresh semen from young men for treatment of sexual weakness was a true organotheray. The Pen-Ts’ao Ching(Great Herbal of the Chinese Pharmacopoeia) dates back to Emperor Shen Nung (2737 BC?) and the Huang-Ti Neiching (Canon of Medicine) to the Emperor Huang-Ti (2697 BC?). The original text of Pen-Ts’ao Ching was lost and known only through an annotated edition. The Great Herbal remedies contained not only of plant origin but also from animal origin. For example, toad’s skin for dropsy, hen’s gizzard for indigestion and gastric ulcer. Mice were used not infrequently both in ancient Chinese and Egyptian remedies.

The modern endocrinology developed in the 20th century. The history of endocrinology seemed synonymous with the history of endocrine glands and with that of internal secretions. This needs some FODUL¿FDWLRQ 7KH DQDWRPLFDO NQRZOHGJH RI GXFWOHVV RUJDQV RU HQGRFULQH JODQGV LV IURP D PXFK HDUOLHU date. Claude Bernard Stated in 1855 that the liver had an external secretion in the form of bile and an internal one of sugar which passes directly into the general circulation. In 1902, Ernest Henry Starling and his closest collaborator also brother in law, William Maddock Bayliss, discovered secretin. They IHOW WKH WHUP ³LQWHUQDO VHFUHWLRQ´ GLG QRW GH¿QH WKH QDWXUH RI D FKHPLFDO VXEVWDQFH OLNH VHFUHWLQ ZKLFK produced in some organ, carried by the blood to other parts of body where excited reactions. In 1905, professor starling used the world “hormone” for the first time in his Croonian lecture at the Royal College of Physicians and subsequently in two addresses given in Germany. The word “hormone” was suggested by Sir William B Hardy and his classical colleague W.T. Vesey in Cambridge. It was derived from a Greek Verb “hormone” meaning to put into quick motion, to excite or arouse. The GLVFRYHU\ RI VHFUHWLQ ZDV D YHU\ LPSRUWDQW SURJUHVV RI VFLHQWL¿F WKRXJKW 7KHUHDIWHU WKH LQYHVWLJDWLRQ in endocrinology followed the “four stages principle”.

1. Recognition of the gland or organ which producing hormones 2. Methods to detect hormones

39

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

3. Extraction of hormones 4. Isolation of pure hormones, determination of its structure and then its synthesis.

During the past fifty years the impacts of physiology, biochemistry, immunology, medical technology, pharmacology and molecular biology make endocrinology expand rapidly and considerably at the rate of an atomic explosion. In this address, I will highlight the great achievement RI VRPH 1REHO ODXUHDWHV LQ HQGRFULQH ¿HOG

40

Abstract

DAROC-TADE-1

HOW TO MAKE A SUFFICIENT AND SIMPLE CGM REPORT ‫ݔ‬პᘅ ‫ݔ‬πߞ۹ᚃଲུചхᗃऌл‫ݾ‬ᚃ৲

The CGM data in\terpretation and final report preparation could be a bothering work if the diabetes education team could not focus on the report consensus. The computerized standard tamplet could be used as the report prototype. The form could include three parts: interpretation, conclusion, and suggestion. The contents in each part could focus on major points which would be frequently HQFRXQWHUHG LQ WKH &*0 H[DP 1RFWXUQDO SHULRG LV DOZD\V WKH ¿UVW WDUJHW LQ WKH &*0 LQWHUSUHWDWLRQ We have to find hypoglycemia first. Second, compare the AC/PC in main meals. Third, diet and exercise impact on glucose variation could be added in the diagnosis. The pattern identification by 6QDSVKRW RU DGYDQFHG DUWL¿FLDO LQWHOOLJHQFH LV DQ HDV\ ZD\ WR SLFN XS WKH NH\ SRLQWV ,Q FRQFOXVLRQ through the systemic approach, we could make CGM report as easy as possible.

41

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DAROC-TADE-2

௄ CGM ᅌϾࣽґ‫ٿ‬ѻӶᑦ‫੿׎‬ᆔ౪‫ِޠ‬Ք ‫ݔ‬з៤ ᄕϾஆ࿝ఁᚃଲ

Self-monitoring of blood glucose is the gold standard to manage glycemic status. Testing strip costs, pain as well as providing only a snapshot of the blood glucose value at the time of testing limit its usability in patients. Continuous glucose monitoring (CGM) reveals the complete glycemic picture than traditional blood glucose meters. CGM allows users to make decisions regarding their day-to-day diabetes management using real-time glucose trends and values. They also provide customizable hypoand hyperglycemia alarms and display trends of the rate of change of glucose levels. Some CGM V\VWHPV KDYH EHHQ LQWHJUDWHG ZLWK LQVXOLQ SXPSV DQG DUH EHLQJ XVHG LQ DUWL¿FLDO SDQFUHDV FOLQLFDO WULDOV However, the duration of CGM system is too short or it is too cumbersome for use in routine practice.

In this regards, sensors with longer duration and smaller size is under development. On the other hand, new technologies developed for non-invasive technique to monitor blood glucose monitoring, such as optical and transdermal approach, are also the potential sensing modalities. Moreover, cloud-based DSSOLFDWLRQV DQG DUWL¿FLDO LQWHOOLJHQFH DUH UHYROXWLRQL]LQJ WKH ¿HOG DV ZHDUDEOHV GHYLFHV LV QRZ LQ WKH DFW There are still many new innovations in the pipeline. In the future, these modalities would change the management of diabetes care.

42

Abstract

DAROC-TADE-3

CGM ᄈ੿΢Ңࣁ࠯ᄙІᑦ‫੿׎‬ᆔ౪‫ޠ‬ኈ៫ ؄ਥཐ ഫ෬ஆ࿝ఁᚃଲঐ਱ᆔ౪৲

Ս‫ש‬՗ᑦᆀขЇ࢏࿌ί՗ᑦঅାմโ࡚Ȃ൸჌ࣻбΚኻ֖౫࢛ঐਣ໣ᘉ‫ޠ‬՗ᑦঅȂህֆᑦ ЅΠ၍౫‫ݸ‬ȂѠ௕኶ᐄ໕ϛ٘пᇴ݃዗Ӷ՗ᑦ‫ݱ‬୞‫ॴޠ‬ᓏȂ‫پ‬ԄȂፐఁϜொ޲ளཽೞୱ‫ ژ‬:ȶ࣐ եӭ‫ޠ‬എΚኻȂᓢࡤᔯข՗ᑦࡪቅഎϛӤȉȷԫਣഀ៊՗ᑦᆀขᔯࢦ൸჌ᓄኈᐡૢȂࡠᔯข޲ ஡໾ॶȃ᛿‫ޑ‬ȃਯҔࡿ໣՗኶ᐄழӲЩᄈᗚ঩‫ࡤݸޒ‬Ȃ౱я‫ޠ‬ൣ֚૗‫ڟ‬ֆঐ਱Ҕຝ௢ᑦ෉໣‫ޠ‬ ໾ॶȃң᛿๊ୱᚡȂᔔֆྲៗყ໦ᇅঐ਱ଇ፤яঐր‫ܓ‬ᎍϹ‫ޠ‬໾ॶ‫ݾܗ‬ᕜРԓȂໍՅණЁ௢ᑦ ୞ᐡȄ

43

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DAROC-TADE-4

ᕋᎵᆔ౪Ӷ CGM ყ໦‫ِޠ‬Քᇅϸ‫ٵ‬ ചવኌ ഫ෬ஆ࿝ఁᚃଲᕋᎵ৲

ഀ៊ီຊᑦᆀข (CGM) ‫ق‬ಜ૗஋ණ‫ٽ‬ഀ៊‫ޠܓ‬՗ᑦၦଊІᗎ༗Ȃ‫ڟ‬ֆᠧۢ໾ॶȃࣁ୞໕ȃ ᛿‫ڐܗޑ‬уѠ૗Ᏻय՗ᑦᡑϾϟӱφȂ‫ٿ‬ձ࣐‫ݾ‬ᕜ።ᐍϟ‫ٸ‬ᐄȂᡲঐ਱ႁ‫؂ژ‬Ԃ‫ޠ‬՗ᑦ௢‫ښ‬ҭ ዀȄ ᕋᎵ৲Ӷყ໦‫ِޠ‬Քл्࣐ : ‫ڟ‬ֆ‫ٯ‬ఁᏳঐ਱Ԟ໲Ҕጃ‫׈ڸ‬ᐍ‫ޠ‬໾ॶखᓄȃ‫ڟ‬ֆॏᆘ໾ॶ Ϝ‫֥ޠ‬ᗟ໕ȃցᘟ໾ॶϜѠ૗ኈ៫՗ᑦ‫ݱ‬୞‫ޠ‬໾ॶӱφ๊ȂՅഇႇ၇ᐡϜ‫׈‬ᐍ‫ޠ‬ȶՍ‫៬ྲש‬ख ᓄȷ( є֥Ȉ᛿‫ޑ‬ȃ໾ॶȃࣁ୞໕๊खᓄ ) ପӬഀ៊‫ޠܓ‬՗ᑦ኶অІᗎ༗ȂѠᙥԫఁᏳঐ਱ஆ ᙄᇅໍ໧‫ޠ‬ᗟ᜹ॏᆘ፟โȂ‫ٯ‬਴ᐄ೼‫ٳ‬ၦଊȂᔔֆঐ਱ᔤۢؑᓢ‫ܗ‬ᘉЗӬᎍ‫ޠ‬ᗟ᜹ឹ‫ڦ‬ҭዀᇅ ໾ॶ࡛ឋȄ ഫ෬ஆ࿝ఁᚃଲଭᄈ၇ CGM ‫ق‬ಜϟঐ਱Ȃ๞ϡᚃᕜყ໦ϟ‫׈‬ᐍྲៗȂყ໦Ԛসєࢃᚃ৲ȃ ᕋᎵ৲ȃៗ౪৲Ȃᚃ৲॓ೱ : ᑣᒶ੿΢ȃ‫ݾ‬ᕜຩᘟȃ኶ᐄց᠟ȇᕋᎵ৲॓ೱ : ఁᏳঐ਱໾ॶखᓄȃ ໾ॶखᓄϸ‫ݚ‬ȃᕋᎵຠզᇅຩᘟȃᕋᎵፐఁȇៗ౪৲॓ೱ : ၇ᐡᇅܷᐡȃ኶ᐄᒰΤᇅίၸȃఁ Ᏻঐ਱ SMBGȃៗ౪ࣻᜱፐఁ๊ȂᙥҦყ໦‫ྲޠ‬ៗȂᡲᑦ‫ྲ੿׎‬ៗϛӕѬ‫׌‬४ܼ᛿‫ޑ‬።ᐍȂ‫؂‬ ૗ཧପ໾ॶ።ᐍ‫ڸ‬ៗ౪ࣻᜱፐఁȂᡲொ޲ᕖூӓР՞‫׈ޠ‬ᐍᚃᕜྲៗȄ

44

Abstract

MTP-D

SURGICAL MANAGEMENT OF THE DIABETIC FOOT: YOUR WOUND, ISCHEMIA AND FOOT INFECTION (WIFI) SETTINGS DAVID G. ARMSTRONG, DPM, M.D., PH.D. Professor of Surgery, Keck School of Medicine USC; Department of Surgery

Numerous modalities have emerged as potentially promising adjuncts to healing diabetic foot wounds. However, none of these will reach their therapeutic potential unless one is able to measure risk and direct medical and surgical therapy. The purpose of this lecture will be to review basic tenets of common sense in therapy of diabetic foot wounds and describe a simple system for assessing limbthreat. Specifically, severity of Wound, Ischemia or Foot Infection (WIFI). We will then describe efforts for surgical intervention for each of these three risk factors. We will also discuss potential therapies for the patient in diabetic foot remission designed to extend ulcer-free, hospital-free and activity-rich days. Further information regarding this lecture including video, manuscripts, diabetic foot blog, etc are available at: www.diabeticfootonline.com .

45

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD1-1

UPDATE ON DIABETES EPIDEMIOLOGY IN THE UNITED STATES EDWARD J. BOYKO, M.D.,M.P.H. Professor, Department of Medicine, Adjunct Professor, Department of Epidemiology, Adjunct Professor, Department of Health Services, University of Washington

Since the early 1990s, the prevalence of type 2 diabetes in the United States has more than doubled from 3.6% in 1990 to 8.7% in 2015 among adults ages 18 years or older. The large increase occurred concomitantly with an epidemic of overweight and obesity. I will discuss whether the increase in body weight explains completely the increase in number of diabetes cases. Since 2015, the SUHYDOHQFH KDV OHYHOHG RII :KHWKHU WKLV UHÀHFWV D VWDELOL]DWLRQ RI WUXH GLDEHWHV LQFLGHQFH RU DQ DUWHIDFW of the method to identify diabetes cases is an active question that I will discuss. Multiple surveys are conducted at regular intervals in the United States that include laboratory testing (NHANES), in person interview (NHIS), and telephone survey (BRFSS). These different surveys are used to estimate occurrence of diabetes and its complications nationally and regionally, as well as identifying risk factors such as overweight/obesity. Laboratory testing to identify diabetes is based on fasting glucose, 2-hour oral glucose tolerance testing, and Hemoglobin A1c. Advantages and disadvantages of each methodology will be discussed. Although obesity is well recognized as a risk factor for diabetes, certain body composition differences at a normal weight have also been identified as risk factors.

Such measurements though are typically not available in populations due to the need for imaging technology. Occurrences of diabetes complications in the United States are captured by multiple national data resources related to hospitalizations and payment for renal dialysis. Progress in reducing end stage renal disease (ESRD) occurrence was seen between 1996 and 2009, but ESRD incidence has since stabilized. Similarly, progress in reduction of diabetic amputations was seen over that same time period but since 2009 the number of hospitalizations for diabetic amputations has increased. I will discuss online database and search engine resources from the Centers for Disease Control and Prevention which once understood will allow any website visitor to track diabetes trends in the United States in real time.

46

Abstract

SD1-2

EPIDEMIOLOGICAL PATTERNS AND CHALLENGES OF DIABETES CARE IN TAIWAN CHIH-CHENG HSU1 1

Institute of Population Health Sciences, National Health Research Institutes

The task force of National Health Research Institutes (NHRI) has collaborated with the DAROC and TADE and used the National Health Insurance Research Database (NHIRD) to conduct epidemiological studies and publish the 2019 Diabetes Atlas, which delineated epidemiological features of diabetes and practice patterns of diabetes care in Taiwan for the last decade between 2005 and 2014. The contents of 2019 Diabetes Atlas included trend analyses for diabetes’ incidence, prevalence, mortality, micro and macrovascular complications, physicians’ accountability, hospitalization, and anti-diabetic medication use. The current status of the diabetes pay-for-performance program was also reported in the series. The publication of the 2019 Diabetes Atlas emphasizes importance of continuous monitoring and surveillance of quality of diabetes care. The collaborative effort from the academia and clinicians also declares determination from the whole society to better diabetes care in Taiwan. In this talk, I will show epidemiological pattern of diabetes in Taiwan, achievements of the diabetes care we have made, and the challenges ahead we must face to improve quality of diabetes care in the future.

47

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD1-3

DESIGN AND PRELIMINARY FINDINGS OF TAIWAN DIABETES REGISTRY (TDR) 1

SHIH-YI LIN ON BEHALF OF TAIWAN DIABETES REGISTRY GROUP

1

Center for Geriatrics and Gerontology, Taichung Veterans General Hospital

Diabetes is a widespread chronic disease, and in Taiwan the total diabetes population is estimated at around 2.2 million out of the 23 million residents. The Diabetes Association of the Republic of China (Taiwan) launched Taiwan Diabetes Registry (TDR) study in October, 2015, which enrolled three patient groups, participants in the diabetes quality control studies in 2006 and 2011(group 1), type 1 diabetes (group 2), and type 2 diabetes diagnosed within 6 months (group 3) from medical centers, regional and local hospitals and general practice clinics. The general characteristics, reports of blood and urine tests, diabetic complications evaluation, and use of medications were recorded at baseline and then every 1-2 years. To evaluate the status of diabetes control, the percentage of attaining targets for (HbA1c) less than 7%, blood pressure (BP) less than 130/80mmHg or 140/90mmHg, lowdensity lipoprotein cholesterol (LDL-C) less than 100mg/dL or total cholesterol < 160mg/dL, and all 3 target at the baseline enrollment were analyzed. Until August, 2018, 13 medical centers, 19 regional and local hospitals and 32 general practice clinics participated in the TDR and a total of 5,600 patients with diabetes, including 1,207 in group 1 (mean ± SD, 65.1 ± 12.1 years; M/F 636/571), 1,092 type 1 diabetes in group 2 (32.7 ± 13.9 years; M/F 442/650), and 3,301 newly diagnosed type 2 diabetes in group 3(54.4 ± 13.9 years; M/F 1,869/1,432) were included. The attained percentage of various metabolic goals in group 1, 2, and 3 was 37.6%, 22.8%, and 38.5%, respectively for HbA1c < 7%, 69%, 56.4%, and 41.0% for LDL-C < 100mg/dL or total cholesterol < 160 mg/dL, 37.0%, 66.2%, and 37.0% for BP < 130/80mmHg, 67.4%, 87.0%, and 68.6% for BP < 140/90mmHg, and 11.7%,10.3%, and 7.6% for all 3 ABC controls with BP < 130/80mmHg, or 20.4%, 12.8%, and 13.6% for all three ABC controls with BP < 140/90mmHg.The data of the TDR are continuously expanding, and we anticipate that it will become a valuable source to address relevant information in diabetes management. It is shown in TDR that the proportion of patients achieving ABC targets get improved gradually in comparison with that in previous surveys in Taiwan.

48

Abstract

SD2-1

DIABETIC KIDNEY DISEASE: UNMET ISSUES JIN-SHUEN CHEN, MD. PHD General Secretary of Taiwan Society Nephrology; Chief, Department of General Medicine, Tri-Service

General Hospital, Taipei, Taiwan; Professor, Department of Medicine, College of Medicine, National Defense University, Taipei, Taiwan Diabetic kidney nephropathy (DKD) and diabetic nephropathy (DN) are the leading causes of end-stage renal disease (ESRD), that contribute to heavy medical costs in Taiwan and most developed countries. Researchers around the world, particularly endocrinologists, nephrologists and associated medical personnel, are working to solve the disease; however, many unmet issues remain for this FRPSOH[ DQG GLI¿FXOW WR WUHDW GLVHDVH ,Q WKLV OHFWXUH WKH GH¿QLWLRQ HSLGHPLRORJ\ GLDJQRVLV PHFKDQLVP WUHDWPHQW DQG SURJQRVLV RI DN will be reviewed and updated according to data from Taiwan and the rest of the world. After a comprehensive review and input from a nephrologist, some of the major unmet issues in DN research will be presented. The first issue is the current problems in early DN-glomerular hyperfiltration; FXUUHQW UHVHDUFK RQ WKH UHODWLRQVKLS EHWZHHQ JORPHUXODU K\SHU¿OWUDWLRQ DQG (65' ZLOO EH SUHVHQWHG The second issue is current problems of diagnosis of DN, and the difference between pathological and clinical diagnosis for DN will be discussed. The third issue concerns the current pathogenesis of DN; factors from diabetic mellitus contributing to development of DN will be discussed. The fourth issue is current treatment of DN, and precision medicine and care will be reviewed and proposed. All of unmet issues discussed in this lecture will be integrated with the findings from my studies, and potential directions for physicians and researchers will be proposed.

49

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD2-2

MANAGEMENT OF DKD WITH OR WITHOUT CARDIOVASCULAR DISEASE DAISUKE YABE, M.D.,PH.D. Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan; Division of Diabetes and Endocrinology, Kansai Electric Power Medical Research Institute, Kobe, Japan

Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease and represents a large and ominous public health problem. Patients with DKD is highly associated with cardiovascular morbidity and mortality. Despite advances in care, ever increasing number of patients suffering from diabetic kidney disease and end-stage renal disease implies that the current management is not adequate in many aspects. Currently, treatment for diabetic kidney disease include blockade of the renin-angiotensin-aldosterone system, and glycemic and blood pressure control. Recently, some DQWLGLDEHWLF DJHQWV ZHUH VKRZQ WR SURYLGH EHQH¿W IRU UHQDO HQGSRLQWV LQ SDWLHQWV ZLWK W\SH GLDEHWHV (T2D). SGLT2 inhibitors were shown to reduce albuminuria, prevent decline in estimated glomerular ¿OWUDWLRQ UDWH LQ 7 ' SDWLHQWV ZLWK RU ZLWKRXW FDUGLRYDVFXODU GLVHDVH ,Q WKLV VHVVLRQ UHFHQW HYLGHQFH RI anti-hyperglycemia agents for DKD will be shared.

50

Abstract

SD2-3

SELECTION AND CHOICE OF ANTI-DIABETIC DRUGS IN DKD, ESPECIALLY IN MODERATE TO ADVANCED STAGE CKD. ‫݁ݔ‬኉ ା໱ҀҴτӤᚃଲ ( ‫ې‬ଋାᚃစᕋ ) ϲऌл‫ݾ‬ᚃ৲

In patients with diabetes and impaired kidney function (DKD), the risk of CV events are higher than those who have normal kidney function. However, better HbA1c still stands for better outcome in patients with CKD. Oral anti-diabetic medications should be adjusted by declining kidney function as well as insulin. The aim of glucose control in DKD patients should emphasize the importance of avoiding hypoglycemia event. In stage 1 and 2 of CKD, the aim of HbA1c could be < 7% but in stage 3 to 5 of CKD, the aim of HbA1c should not less than 7% to minimize hypoglycemia events.

The oral anti-diabetic agents should be adjusted by the progression of renal function in each patient. In pre-ESRD or anemia patients, the HbA1c could be affected by red blood cells and could not stand for the glucose control condition of patients. Glycated albumin represented the average of glucose level in those patients in the past 2-3 weeks and could replace HbA1c in this condition. Selfmonitor blood glucose (SMBG) were also suitable for these patients.

Metformin should be used carefully and adjusted dose by renal function between 30-45 ml/ min/1.73 m2. Metformin should not be used in patients with eGFR < 30 ml/min/1.73 m2 'DSDJOLÀR]LQ only be prescribed in patients with eGFR > 60 ml/min/1.73 m2 (PSDJOLÀR]LQ LQ SDWLHQWV ZLWK H*)5 !

45 ml/min/1.73 m2 DQG FDQDJOLÀR]LQ VKRXOG EH WDSHUHG WR PJ GD\ LQ H*)5 PO PLQ P2.

However, the effects of SGLT2i is decreased while the renal function is decreasing and should be used carefully. In recent CVOT studies, SGLT2i and GLP-1 both can reduced the CV events in patients with diabetes especially at higher risk patients.

In recent years, the functions of anti-diabetic agents were getting more and more mechanisms and could deal our patients with diabetes not only the glucose control but also preventing them from major CV events even mortality. They provide us a new tool to treat our patients with diabetes more safely and effectively. It is important that how to use these medications safely and effectively on our patients with diabetes.

51

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD3-1

GLYCEMIC CONTROL AND VASCULAR COMPLICATIONS: A FOCUS ON RECENT LONG-TERM FOLLOW-UP OF GLUCOSE LOWERING TRIALS AND THE TRIUMVIRATE OF GLUCOSE MANAGEMENT PETER REAVEN, M.D. Professor of Clinical Medicine; University of Arizona; Phoenix, Arizona

Cohort studies have demonstrated that both macrovascular and microvascular events increase as the level of blood glucose rises. In contrast, trials using more modern treatment regimens conducted in more advanced type 2 diabetes patients (such as the VA Diabetes Trial, ACCORD, ADVANCE), demonstrated that improved glucose control over a median of 3-6 years provided modest reductions in CVD events and did not reduce CVD or total mortality. However, 10-year follow-up of the VADT GHPRQVWUDWHG DQ HPHUJLQJ &9' EHQH¿W IURP WKH RULJLQDO LQWHQVLYH JOXFRVH ORZHULQJ Longer post-trial follow-up of glucose lowering efforts is providing additional insight into key UHPDLQLQJ LVVXHV ZLOO JUHDWHU &9' EHQH¿W EHFRPH DSSDUHQW ZLWK JUHDWHU WLPH LV WKHUH HYLGHQFH for a “legacy effect” in patients with established type 2 diabetes, 3) is there any long-term harm that results from these interventions. As several of the recent studies of type 2 diabetes had very long follow-up period, they are well positioned to determine whether improved glucose control in the past results in risk reduction for new CVD events after glucose levels have equalized between treatment groups. Importantly, as reductions in death may take many years to become apparent, extended followup may also be necessary to understand the effects of intensive glucose lowering on this outcome.

However, there is also growing appreciation that optimal glucose management for reducing diabetes complications requires not just lowering average glucose levels, but also reducing glucose variation and episodes of hypoglycemia. Increasing evidence indicates that both of these latter metrics of glucose control are also related to development of diabetes complications. Particularly useful measures which capture sequential visit-to-visit “long-term” variation and appear good markers of GLDEHWHV FRPSOLFDWLRQV LQFOXGH FRHI¿FLHQW RI YDULDWLRQ DQG DYHUDJH UHDO YDULDELOLW\ The current presentation will review outcomes of longer-term follow-up of glucose lowering studies and highlight the potential importance of managing all three aspects of glucose control including hyperglycemia, glycemic variation and hypoglycemia.

52

Abstract

SD3-2

PHYSIOLOGY AND FRIENDSHIP PHILIP S. TSAO, PH.D. Professor of Medicine (Cardiovascular Medicine); Stanford University School of Medicine Associate Chief of Staff for Precision Medicine; VA Palo Alto Health Care System Director; VA Palo Alto Epidemiology Research and Information Center (ERIC) for Genomics Co-Principal Investigator; Million Veteran Program

Almost thirty years ago I walked onto the campus of Stanford University as a freshly minted cardiovascular physiologist looking to make an impact upon clinical medicine. I soon met a kindred spirit in Jerry Reaven who, as the archetype physiologist, had already made a career (and helped start many more) of adding insight into how dyslipidemia, hypertension, and type 2 diabetes clustered together to produce a syndrome that increased the risk of cardiovascular disease. Through his unyielding curiosity and elegant communication skills, Jerry not only taught me how to be a better scientist but also to enjoy a life of exploration. I look forward to sharing some memories of our collaboration with you.

53

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD4-2

OLD SOLDIERS NEVER DIE THEY JUST “FRAIL” AWAY--SARCOPENIA AND FRAILTY IN DIABETIC PATIENTS CHING-LING LIN M.D. Endocrinology and Metabolism Department of Internal Medicine Cathay General Hospital.

Aging is rapidly accelerating in Taiwan. As the average life expectancy becomes longer island wide, prolong life expectancy is no longer the only goal for most diabetic patients. Longer life expectancy is meaningful only when activity of daily life (ADL) and the ability of living independently can be maintained. Sarcopenia and frailty are both highly relevant entities with regards to ADL and autonomy of the aging population. Skeletal muscle maintains our posture and produces body movement. It not only is important for maintaining normal activity but also contributes to basal metabolic rate in the body. Insulin receptors in the muscle play a major role in glucose regulation, and muscle is a major site of glucose disposal. Muscle is also a fuel source under certain conditions, such as starvation, and provides amino acids for gluconeogenesis in the liver. Recent studies have shown that skeletal muscle secretes several factors, so-called myokines, which are associated with maintaining healthy conditions. In patients with metabolic syndrome or type 2 diabetes reduced muscle glucose GLVSRVDO LV D PDMRU FRPSRQHQW RI LQVXOLQ UHVLVWDQFH 6DUFRSHQLD LV GH¿QHG DV DJH UHODWHG JOREDO ORVV of skeletal muscle mass and strength. Aging related reduction of muscle mass may further jeopardized metabolic dysregulation in type 2 diabetic patients. Frailty is a state of increased vulnerability to stressors, responsible for exposing the older person to enhanced risk of adverse outcomes. Physical frailty and sarcopenia substantially overlap and several adverse outcomes of frailty are likely mediated by sarcopenia. Patient with diabetes mellitus already tend to have an accelerated ageing process that places them at greater risk for developing frailty at an earlier age. The development of frailty and sarcopenia is multifactorial and includes nutritional, physical and hormonal elements; these elements are interlinked with those of diabetes. A lower muscle mass will lead to higher insulin resistance, lower muscle glucose disposal and poorer glycaemic control. Lower muscle glucose disposal leads to higher insulin secretion and insulin resistance, which is the stepping stone for diabetes itself. The biological EDFNJURXQG RI VXFK D FORVH UHODWLRQVKLS QHHGV WR EH H[SORUHG DQG FODUL¿HG DV LW FDQ SRWHQWLDOO\ SURYLGH novel and pivotal insights for the assessment and treatment of these conditions not only in elderly but all diabetic patients.

54

Abstract

SD4-3

THE EPIDEMIOLOGY AND PATHOPHYSIOLOGY OF DIABETES IN THE OLD PEOPLE I-TE LEE Chief in Division of Endocrine/Metabolism in Taichung Veterans General Hospital; Associate Professor in School of Medicine Faculty of Medicine in National Yang-Ming University; Deputy Secretary General in Diabetes Association of the Republic of China

ᇄ ᢋ 65 ྒ п α ఋ ထ ົ ႇ 330 ࿳ ΢Ȃ ϑ ົ ႇ ᖃ ΢ π ‫ ޠ‬14%Ȃ ֊ ᗛ Τ ା ឮ ަ ཽ (aged society)Ȅᓎ຀ՃԒ΢πСઊቩђȂᑦ‫੿׎‬ȃѷහ઀ȃ૿৶ІՋЎ઀๊ᄛ‫ޠ੿ܓ‬ឋᚡη຺‫຺ٿ‬অ ூ२ຝȄՃԒᑦ‫੿੿׎‬΢ԥ‫ڐ‬ᑀ੬‫ܓ‬ȂӱԫՃԒಒΡ࠯ᑦ‫ޠ੿׎‬ຩᘟຠզȃ՗ᆔР८‫઀ึڂ‬ȃ ՗ᑦ௢‫ښ‬ȃ᛿‫ݾޑ‬ᕜȃմ՗ᑦ઀‫ޒ‬ȃᑦ‫ྲ੿׎‬ៗ๊ឋᚡᔗϡпᕤ၍Ȅ ѫѵȂՃԒᑦ‫੿੿׎‬΢‫ޠ‬Ң౪ѓ૗ᓎ຀ԒឮഃᅛଞϾȄଷΠѠ૗ณ‫ݳ‬ᑀҴࣁ୞ᇅՍ‫៬ྲש‬ ѵȂՃԒᑦ‫੿੿׎‬΢ৡܿԥ‫ڐ‬уӔԇ੾੿Ȃሰ्௦‫ڨ‬Ӽᆎ᛿‫ݾޑ‬ᕜȄ ӱԫȂ‫ݾ‬ᕜՃԒொ޲‫ޠ‬ᑦ‫࢑੿׎‬Κ໷࡟τ‫ࢆޠ‬᏾Ȅؑ՞ՃԒᑦ‫੿׎‬ொ޲‫ݸ੿ޠ‬എϛӤȂ ᚃᕜ΢স҇໹ᕤ၍ՃԒᑦ‫੿׎‬ொ޲‫ޠ‬Ң౪І੿౪ᡑϾዂԓȂ҉ആঐ΢Ͼ‫ޠ‬ᑦ‫੿׎‬ຩᕜІྲៗ ॏฬȄ

55

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD5-1

AI FOR DIABETES MANAGEMENT: THE LAST MILE OF DIGITAL HEALTH ֕ᅖതീς ๽ᆉ໵ᆓᄳ๽ᆉୋஷᖃစ౪

Recent digital technologies, such as cloud, IoMT, bigdata, AI, blockchain, has been applied to personalized medicine, or precision medicine for years. Dr. Wu will present several use cases in this session, including an IoMT Platform, a decentralized patient network for clinical research, and some medical AI projects. Dr. Wu will also discuss opportunities and challenges of digital health in Taiwan.

56

Abstract

SD5-2

EARLY DETECTION OF ACUTE COMPLICATIONS IN IDDM PATIENTS USING NOVEL MULTI-BIOMARKER CGM DEVICE 1

C-C HUANG, 2LIZ GODWIN, 2Y-L DING

([HFXWLYH 0DVWHU RI %XVLQHVV $GPLQLVWUDWLRQ 1DWLRQDO &KLDR 7XQJ 8QLYHUVLW\ &KLHI ([HFXWLYH 2I¿FHU Seknova Biotechnology Co., Ltd. Taiwan, R.O.C. 2Department of Marketing and Sales, Seknova Biotechnology Co., Ltd. Taiwan, R.O.C.

1

BACKGROUND: Diabetes mellitus is a rapidly growing global epidemic, impacting over 400 million people. The number of diabetics is expected to exceed 600 million in the next twenty years.

Crucial to diabetes management is patient self-monitoring of blood glucose (SMBG), largely through WUDGLWLRQDO ¿QJHU SULFN PHWHUV +RZHYHU DFWXDO WHVWLQJ IUHTXHQF\ LV PXFK ORZHU WKDQ UHFRPPHQGHG resulting in poor glycemic control. More importantly, SMBG monitoring does not detect severe acute complications, including diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS), and hypoglycaemia.

METHODS: Research on a multi-biomarker CGM device is being conducted at the National Applied Research Laboratories in Taiwan in conjunction with the device inventor, Seknova Biotechnology. The device is worn on the upper arm and continuously monitors glucose, ketones and ODFWDWH LQ WKH LQWHUVWLWLDO ÀXLG (IIHFWLYHQHVV RI WKH V\VWHP ZDV HYDOXDWHG E\ FRPSDULVRQ RI &*0 YDOHV to SMBG values collected using a traditional blood glucose meter. Performance was evaluated in terms of proportion of the system values within ± 20% of blood glucose meter reference values for glucose levels > 80 mg/dL and ± 20 mg/dL at meter glucose levels < 80 mg/dL. RESULTS: Mean absolute relative difference (MARD) was < 10% and %20/20 was 92%.

CONCLUSION: Initial laboratory testing of the Seknova CGM system shows high effectiveness LQ WKH FRQWLQXRXV PRQLWRULQJ RI JOXFRVH LQ WKH LQWHUVWLWLDO ÀXLG 8QOLNH RWKHU &*0 GHYLFHV WKDW UHTXLUH needles to penetrate the subcutaneous tissue, the Seknova CGM technology measures biomarkers in the dermal tissue, minimizing pain and risk of infection and injury. The unique design also allows for the simultaneous monitoring of multiple biomarkers.

57

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD5-3

DASHBOARD FOR IMPROVING DM CARE: TCVGH EXPERIENCE 1

YI-JING SHEEN

1

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

Diabetes mellitus and diabetes-related complications may cause disabilities, vital organ failure, premature death, and a high burden on individuals and society. Patients with diabetes have a greater chance of hospitalization and readmission compared to those without diabetes. Integrated information WHFKQRORJ\ DQG GDVKERDUG PD\ LPSURYH WKH HI¿FLHQF\ DQG DFFXUDF\ RI DFTXLULQJ LQIRUPDWLRQ IRU KLJK quality diabetes care. We will share the experience of an electronic dashboard management system for improving diabetes care at Taichung Veterans General Hospital.

58

Abstract

SD6-1

INSULIN RESISTANCE: THE GENETIC AND PHYSIOLOGIC INTERRELATIONSHIP BETWEEN TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE; AND THE INTERFACE BETWEEN TAIWAN AND CALIFORNIA: BOTH THE LEGACY OF PROFESSOR YII-DER IDA CHEN. JEROME I. ROTTER, M.D. Professor of Pediatrics, UCLA School of Medicine Professor of Human Genetics, UCLA School of Medicine; Director, Institute for Translational Genomics and Population Sciences, LABioMed/Harbor-UCLA; Director, Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Harbor-UCLA

One of the seminal observations in diabetes/endocrine/cardiac pathophysiology over the last 4 decades was the characterization of insulin resistance (IR) as the key physiologic (and pathophysiologic) abnormality for type 2 diabetes (T2D); but not only for T2D, but for cardiovascular disease (CVD) risk factors such as dyslipidemia (especially hypertriglyceridemia and low HDL) and obesity, for cardiac physiologic abnormalities such as hypertension, and for the end product of coronary artery disease itself. This also has been referred to as the metabolic syndrome. And major contributors (perhaps the major contributors) to this concept was the scientific duo of Dr. Gerald Reaven and Dr. Ida Chen. Starting in the 1980’s, they developed the evidence for IR as a key (possibly the key) CVD risk factor. Many of these seminal observations were done in collaboration with Taiwanese collaborators. At the end of the 1990’s and beginning of the current century, Dr. Chen expanded this work into examining genetic determinants of IR and its CVD associations through WKH ODQGPDUN 6$33+,5H 6WDQIRUG $VLDQ 3DFL¿F 3URJUDP LQ +\SHUWHQVLRQ DQG ,QVXOLQ 5HVLVWDQFH

TAICHI (Taiwan Metabolic Study for Cardiovascular Disease), THRV (Taiwan Study for Hypertension Rare Variants), and THRV TOPMed (Trans-Omics for Precision Medicine). This collaboration of Taiwan-California (i.e. Dr. Chen) remains extremely active, and has contributed, since 2013 alone, to some 44 papers, with multiple papers delineating the genetic basis of insulin resistance, diabetic retinopathy, blood pressure variation, lipid variation, adiposity, coronary artery disease, and type 2 diabetes. This work has helped delineate the genetic architecture of diabetes and insulin resistance disorders, and should lead to improved biologic understanding and advances in therapy of the most common metabolic disorder, i.e. insulin resistance.

59

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD6-2

TRNASLATIONAL RESEARCH OF ADIPONECTIN- A TALE OF COLLABORATION L-M CHUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Adiponectin, an adipocytokine, plays important biological roles involving insulin sensitizing, anti-inflammation, anti-atherosclerosis, and anti-cancer effects. However, its regulation is not fully understood. :H KDG RULJLQDOO\ LGHQWL¿HG D JHQH FRGLQJ DGLSRQHFWLQ WKDW ZDV XS UHJXODWHG GXULQJ DGLSRF\WH differentiation with a mRNA differential display. The expression of adiponectin in human was studied in twin and family studies, revealing that both genetic and environmental influences on circulating adiponectin levels. To understand the regulation of expression, we employed classical genetic approaches including candidate gene approach, genome-wide linkage study, regional and genome-wide association studies.

Through a genome linkage study in the Stanford Asia-Pacific Program for Hypertension and ,QVXOLQ 5HVLVWDQFH 6$33+,5H IDPLO\ VWXG\ ZH IXUWKHU ¿QH PDSSHG D H47/ ORFDWHG RQ FKURPRVRPH 15 at 31cM with 1-LOD SI: 24 to 34cM. After regional SNP studies, we found that haplotypes composed of single-nucleotide polymorphisms in the ryanodine receptor 3 (RYR3) gene had a strongest association with plasma adiponectin levels. To validate the biological function of RYR3 on adiponectin expression, we demonstrated in human and a type 2 diabetes model db/db mice studies showing silencing expression of RYR3 in adipocytes/adipose tissue would increase circulating DGLSRQHFWLQ OHYHOV WRJHWKHU ZLWK D UHGXFHG LQ DGLSRVH WLVVXH LQÀDPPDWLRQ DQG DQ LQFUHDVH LQ ZKROH body insulin sensitivity.

Our study provide understanding of novel mechanisms that regulate expression of adiponectin, leading to improving insulin sensitivity. Further translational potential remains to be evaluated. These work was indebted to extensive collaboration both domestically and internationally.

60

Abstract

SD6-3

MY JOURNEY OF RESEARCH FROM INSULIN SENSITIVITY TO GENETIC STUDY: LEARN FROM IDA CHEN ࢺΛϧ ήॗᖃᚃଲ‫ݙ‬ύϸଲϲऌഌϲϸ‫ݫ‬ᄳུചхᗃऌ

When I was a young clinical fellow in the division of Endocrinology of Tri-Service General Hospital, Prof. Chen and Reaven were our visiting professors and they almost would visit our hospital HYHU\ \HDU 6LQFH WKDW WLPH , EHJDQ WR NQRZ ZKDW LV ³LQVXOLQ UHVLVWDQFH´ GH¿QLQJ WKH FDSDELOLW\ RI JOXFRVH GLVSRVDO YLD LQVXOLQ PHGLFDWHG SDWKZD\ ,W FDQ EH TXDQWLWL¿HG E\ VWDQGDUG PHWKRGV VXFK DV JO\FHPLF FODPS PRGL¿HG LQVXOLQ VXSSUHVVLRQ WHVW RU LQWUDYHQRXV JOXFRVH WROHUDQFH WHVW , KDG XVHG WKH PHWKRG RI PRGL¿HG LQVXOLQ VXSSUHVVLRQ WHVW WR DFFHVV WKH LQVXOLQ VHQVLWLYLW\ LQ 6+33+LUH VWXG\ DQG LQ obese subjects under the instruction of Prof. Chen and Dr. Jerng.

In Oct, 2001, I had a chance of one-year clinical fellow training in the division of endocrinology under the instruction of the professor Chen, Rotter and Braunstein in Cedars-Sinai Medical Center in LA. We conducted microarray studies on thyroid samples of benign adenoma, examined by Affymetrix chips. We also immersed extensively in the bioinformatics and analysis of these expression data including at least 10,000 named genes. We had discovered many interesting probes differentially expressed between the two condition, some up-regulated and some down. :KHQ , FRPH EDFN WR 7DLZDQ , ZRXOG FRQWLQXH P\ UHVHDUFK LQ WKH ¿HOG RI LQVXOLQ UHVLVWDQFH ZLWK our instructors and collaborated with Prof. Chen, including SAPPHire study. Finally, I really appreciate Prof. Chen in my research career and glad to be together with her.

61

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD6-4

CHROMOSOME 9P21 POLYMORPHISM AND CARDIOVASCULAR DISEASE ؄࠶኉ ᇄϜᄹҖᖃᚃଲ ϲऌഌ ϲϸ‫ݫ‬ᄳུചхᗃऌ

I must express my deep respect and appreciation to Prof. Ida Chen. Before my exchange-visitor program, Prof. Ida Chen had visited Taichung VGH, and she established several study programs for cooperation. Being a member of the study team group, I had a chance to learn genetic study in CedarsSinai medical center under Prof. Ida Chen’s supervision between Oct. 2009 and Oct. 2010. ,W LV P\ ¿UVW H[SHULHQFH WR KDYH D IXOO WLPH FRXUVH LQ EDVLF ODERUDWRU\ 3URI ,GD &KHQ KHOSHG PH to be familiar with the persons, the backgrounds and the activities of our laboratory. I have practiced WKH P51$ DPSOL¿FDWLRQ DQG '1$ H[WUDFWLRQ DQG DWWHQGHG WKH SURFHGXUHV RI UXQQLQJ *:$ FKLSV ,Q the study meeting, I gained knowledge about the organization and discussion on the study issues.

In addition to explaining the detail of each ongoing project, Prof. Ida Chen also encouraged me join the study team lead by Prof. Rotter. Under Prof. Ida Chen’s introduction, I could approach the UCLA intercampus training program, from which I learned various methods for genetic studies, including quantitative trait analysis and family-base association tests. In Medical Genetics Seminar Series, I experienced many examples of practice in genetic studies.

Before my training course finished, we had completed the DNA preparation for running Chip based on the clinical manifestation of diabetic retinopathy. We also completed the genetic data and clinical phenotypes of coronary artery disease. I finished my first article of genetic research. I also JRW WKH FHUWL¿FDWLRQ RI 9LVLWLQJ 6FLHQWLVW LQ *HQHWLFV RI &RPPRQ 'LVHDVH LQ WKH 8&/$ LQWHUFDPSXV medical genetics training program.

Finally, I thank Prof. Ida Chen for her help in whole my training period. She helped me resolve all of my problems in American life. It is a precious experience for me. Prof. Ida Chen still encourages me to keep forward to genetic studies. Now, she has several ongoing projects for cooperation with us, and several articles have been being published. I deeply appreciate Prof. Ida Chen’s help in my carrier.

62

Abstract

SD7-1

UPDATE OF INTERNATIONAL GUIDELINES FOR DIABETES MANAGEMENT 1

H-Y LI

1

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

After the release of the DAROC guideline for diabetes care 2018, there are several international guidelines published. In late 2018, the ADA and the EASD have published a consensus for diabetes management. Later, the ADA standards of medical care in diabetes adapted the content of the consensus. Patient centered collaborative care is emphasized, and the goal of care is to prevent complications as well as to optimize quality of life. Several key steps in the decision cycle are VXJJHVWHG 0HWIRUPLQ UHPDLQV WKH ¿UVW OLQH WKHUDS\ IRU W\SH GLDEHWHV SDWLHQWV )RU WKH VHFRQG OLQH medication, the consensus suggests that the presence of established atherosclerotic cardiovascular GLVHDVHV $6&9' RU FKURQLF NLGQH\ GLVHDVHV &.'

VKRXOG EH FRQVLGHUHG ¿UVW DQG 6*/7 LQKLELWRUV and GLP-1 receptor agonists are recommended in the presence of ASCVD or CKD. Besides, the consensus also suggest choices of second-line medications based on different goals, such as to minimize weight gain, to avoid hypoglycemia and to consider the cost. For injection therapy, the consensus also provided an algorithm for the choice among them. In 2019, the AACE updates their clinical practice guideline about type 2 diabetes management. ASCVD is also an important consideration in the guideline. In this talk, I will introduce the content of the ADA/EASD consensus and the AACE guideline first. Then, I will also discuss the pros and cons of the two international guidelines.

63

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD7-2

DAROC CLINICAL PRACTICE GUIDELINES FOR DIABETES CARE2019 UPDATE CHIH-HSUN CHU Chief, Division of Endocrinology and Metabolism, Department of Medicine, Kaohsiung Veterans General Hospital

T2DM is a complex chronic disease. It requires continuous medical care with multifactorial risk reduction strategies. The goals of treatment for diabetes are to prevent or delay complications and maintain quality of life. The cornerstone of treatment of T2DM is the adoption of a healthy diet, increased physical activity and maintenance of a normal body weight. A number of oral and injectable medications are available to help control blood glucose levels. Metformin is well-established and one of the most effective antidiabetic drugs. Sulfonylureas, which increases insulin secretion in T2DM, is also an essential medicine for diabetes. In recent decades, there has been an increasing complexity of medical treatments for diabetes, mostly due to the availability of new drugs and therapeutic classes. )ROORZLQJ WKH ORQJ WHUP XVH RI PHWIRUPLQ DQG VXOIRQ\OXUHD ¿YH DGGLWLRQDO FODVVHV RI RUDO DQWLGLDEHWLF drugs have come into the market: these comprise alpha-glucosidase inhibitors, thiazolidinediones, the non-sulfonylurea insulin secretagogues glinides, dipeptidyl peptidease-4 inhibitors, and sodiumglucose cotransporter 2 inhibitors. Meanwhile, rapid-acting insulin analogues and long-acting insulin analogues have also become widely used due to their improved pharmacokinetic and pharmacodynamic properties. Except for insulin, GLP-1 receptors agonists, an injectable agent also came into Taiwan.

These antidiabetic drugs act on different pharmacological mechanisms and have completely different safety pro¿les, although clinical trials suggest that they have comparable ef¿cacy in terms of their overall glucose lowering effect. The ADA “Standards of Medical Care in Diabetes” recommends a patient-centered approach should be used to guide the choice of pharmacologic agents. Considerations include comorbidities (atherosclerotic cardiovascular disease, heart failure, chronic kidney disease), hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences. The updated “DAROC Clinical Practice Guidelines for Diabetes Care” in 2019 provides considerations of several factors for the choice of antidiabetic drugs.

64

Abstract

SE1-1

THYROID NODULES: CONSENSUS & CONTROVERSY HOSSEIN GHARIB, M.D., MACP, MACE Professor of Medicine, Mayo Clinic College of Medicine; Past President, American Association of Clinical Endocrinologists; Past President, American Thyroid Association

This presentation includes a critical review and commentary on the recently published guidelines by the AACE (American Association of Clinical Endocrinologists) & ATA (American Thyroid Association), as well as, a discussion of a recent survey on management of thyroid nodules. We will GLVFXVV ULVN RI PDOLJQDQF\ DVVHVVPHQW E\ KLVWRU\ SK\VLFDO H[DP 86 XOWUDVRXQG )1$ ¿QH QHHGOH aspiration biopsy).

The AACE uses a 3-tier system for US risk assessment vs a 5-tier system by ATA. We shall FRPSDUH WKH FRQYHQWLRQDO FODVV F\WRORJLF FODVVL¿FDWLRQ YV D FODVV %HWKHVGD &\WRORJLF 5HSRUWLQJ System, and their impact on nodule management. Several molecular markers are now available for use in indeterminate cytology; the guidelines differ in recommending their application. We shall discuss criteria on how to select nodules for FNA. Recently, some advocate active surveillance for nodules <1 cm with suspicious US appearance, whereas others favor performing FNA and proceeding with surgery if malignant. Follow up of benign thyroid nodule and note that thyroxine suppressive therapy is no longer recommended. Finally, we will compare the risk of cancer in solitary vs MNG and alcohol ablation for cystic lesions.

65

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE1-2

CONSENSUS AND CONTROVERSIES OF MANAGEMENT OF THYROID MICROCARCINOMA. YOUNG-KEE SHONG, M.D., PH.D. Professor, Asian Medical Center, University of Ulsan, Seoul, Korea

In Korea, the incidence of thyroid cancer increased explosively in the early 2000s, and reached a plateau in the early 2010s. Most cases of newly diagnosed thyroid cancer are small indolent microcarcinoma and could be good candidates for active surveillance (AS) instead of immediate surgery. Many considerations must be taken into account for establishing selection criteria for candidates for AS of papillary thyroid microcarcinoma (PTMC), including the characteristics of the tumor, the patient, and the medical team. If possible, AS of PTMC should be a part of a prospective clinical trial to ensure long-term safety and to identify clinical and/or molecular markers of the progression of PTMC. Biological behaviors learned from the previous surgical interventions for PTMC will be discussed. And the concept, application, caveats, unanswered questions, and future perspectives of AS of PTMC will be discussed. For appropriately selected patients with PTMC, AS can be a good alternative to immediate surgery.

66

Abstract

SE1-3

NATURAL ORIFICE TRANSLUMINAL ENDOSCOPIC AND ROBOTIC THYROID SURGERY: THE PROMISING RESULT WITH IDEAL OUTCOMES YU HSIEN, CHEN1 1

Keelung Chang Gung Memorial hospital, Taiwan

Introduction: Transoral thyroid surgery was regarded as minimally invasive surgery and provide H[FHOOHQW FRVPHWLF UHVXOW ZLWKRXW DQ\ YLVLEOH VFDU 7KH GD 9LQFKL URERWLF V\VWHP SURYLGHV PDJQL¿HG ' HD view and wristed instruments that rotate far greater than human hand. Therefore, it could provide better peri-neural dissection. Here, we present the experience of transoral robotic thyroidectomy by a single surgeon.

Material &Method: From JAN 2018 to JUN 2018, 24 patients received transoral robotic thyroidectomy vestibular approach using da Vinci Xi for benign and malignant thyroid nodules.

The robotic arms were docking through oral vestibular and right axilla. The indication includes benign thyroid nodules < 8 cm and malignant thyroid nodules < 2 cm. The Surgical outcomes were retrospectively reviewed.

Results: 24 patients ( 19 females, 5 males; mean age 41.75 ± 11.67 (range, 20-62) years) received transoral robotic thyroidectomy. 3 patients received bilateral total thyroidectomy, 6 patients received left lobectomy, 15 patients received right lobectomy. 10 cases have cancer include papillary carcinoma and papillary microcarcinoma. 2 cases have NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features). 12cases have benign thyroid nodules. The mean operation time was 350.75 ± 92.60 mins. The mean hospital stay was 2.95 ± 1.08 days. The VAS pain score was Day0: 2.30 ± 0.55 ; POD1: 1.91 ± 0.88 ; POD2: 1.91 ± 0.82 . POD3: 1.71 ± 0.82. no reports of vocal cord palsy, surgical site infection or numbness of lower lip.

Conclusion: Transoral robotic thyroidectomy is a feasible natural orifice thyroid surgery with little complication and excellent cosmetic result.

67

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE2-1

AI AND ROBOTICS – KEY TO ERA OF SMART MEDICINE LI-CHEN FU 'LUHFWRU 178 &HQWHU IRU $UWL¿FLDO ,QWHOOLJHQFH DQG $GYDQFHG 5RERWLFV 3URIHVVRU 'HSW RI (OHFWULFDO Engineering, Dept. of Computer Science & Information Eng., National Taiwan University

,W LV QRQ GHQLDEOH WKDW WKH FXUUHQW ZRUOG KDV EHHQ VKDNHQ XS KDUG E\ WKLV QHZ ZDYH RI $UWL¿FLDO Intelligence (AI), and people in the world realized this mostly after AlphaGo has burst its gigantic power in playing chess beating the top-notch chess players from all over the world. Since then, AI has step-by-step steadily changed our life almost in every aspect, and successful evidences have been observed, e.g LQ VPDUW PDQXIDFWXULQJ VPDUW VHUYLFHV VPDUW ¿QDQFH DQG VPDUW PHGLFLQH etc.

Through analysis of the big data, this new AI tide leads people’s lives to the better stage by leveraging the so-to-speak collective intelligence. As for Robotics, thanks to quick AI development, service robots have become more popularly working in our human living environment, after overcoming all sorts of uncertainties encountered while the robots are serving the humans.

Given this new era of human world full of various AI technologies and smart robot agents, it is not surprising that mankind’s life expectancy as well as life quality will be augmented since humans will be constantly guarded within a system of precision medicine, preventive medicine, and social service robots. For example, AI enhanced medical imaging, disease forecast, safe drug prescription, mental healthcare, clinical decision support, and so on and so forth will help people be more aware of their possible health threats in much earlier stage (so as to prevent them) and be treated by far more smart therapeutic measures after their health conditions are threatened (in order to get better cures).

For more to come, the elderly will be accompanied and cared by a bunch of smart robot agents even when the supporting younger generation simply become more and more scarce resources. We believe that the futuristic “Society 5.0” proposed by Japan in 2016 can be gradually realized in this new era where mankind will live with health, joy, and prosperity.

68

Abstract

SE2-3

THE ARTIFICIAL INTELLIGENCE IN BIOINFORMATICS ALGORITHMS 1,2

CHIEN-YU CHEN

1

Taiwan AI Labs, 2Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taiwan, R.O.C.

The techniques of machine learning and deep learning play an important role in the design of ELRLQIRUPDWLFV DOJRULWKPV DQG WKHLU DSSOLFDWLRQV LQ JHQRPLF PHGLFLQH 7KLV WDON ZLOO EULHÀ\ SUHVHQW three examples of using machine learning or deep learning in analyzing biomedical data. The first H[DPSOH SUHVHQWV WKH XVDJH RI FOXVWHULQJ DQG FODVVL¿FDWLRQ WHFKQLTXHV RQ JHQH H[SUHVVLRQ GDWD XVLQJ microarrays or RNA sequencing (RNA-seq). The second example illustrates how pattern mining and classification can be used to analyze protein sequences and structures, including predictions of functionally important residues and structure characteristics. The last example shows the recent DSSOLFDWLRQV RI GHHS OHDUQLQJ RQ HSLJHQRPLF GDWD DQDO\VLV UHYHDOLQJ WKH YDOXH RI DUWL¿FLDO LQWHOOLJHQFH in analyzing personal genomes for precision medicine. All the above-mentioned methods will be released in TaiGenomics, a newly AI genomic platform developed by Taiwan AI Labs, for biomedical applications in the near future

69

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE3-1

DIFFERENTIAL DIAGNOSIS, INVESTIGATION AND THERAPY OF ADRENAL INCIDENTALOMAS YU-WEN SU Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C..

$Q DGUHQDO LQFLGHQWDORPD LV GH¿QHG DV DQ DGUHQDO PDVV GHWHFWHG RQ LPDJLQJ QRW SHUIRUPHG IRU suspected adrenal disease. Earlier autopsy studies suggested a prevalence ranging from 1.0-8.7%, and increases to 10% in the elderly population. Therefore, it become one of the most common encountered clinical complaint in endocrinology clinic nowadays.

The most critical part in investigation of adrenal incidentaloma is to recognize possible malignant WXPRU ZKLFK FDQ EH VXVSHFWHG DFFRUGLQJ WR VRPH LPDJH FKDUDFWHULVWLFV $IWHU WKDW WR FRQ¿UP KRUPRQH over-secretion is another important issue. Both recognizing malignancy, and confirming hormone secretion status are crucial for further decision making for treatment and follow up schedule. While established hormone hypersecretion syndrome, including Cushing syndrome, Conn’s syndrome, and pheochromocytoma are indications for surgery, there is still an area of uncertainty concerning tumor with “possible autonomous cortisol secretion”, previously denoted as “subclinical Cushing’ syndrome”.

In this section, we aim to provide a comprehensive overview on the differential diagnosis, investigation, and decision for therapy based on current guidelines and clinical evidence.

70

Abstract

SE3-2

INTERVENTIONAL RADIOLOGY OF THE ADRENAL GLANDS: CURRENT STATUS C-C CHANG Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Adrenal venous sampling (AVS) was introduced in late 1960s as a test to distinguish unilateral from bilateral primary aldosteronism (PA). AVS is held to be the “gold standard” diagnostic procedure for assessing lateralization of aldosterone secretion and thereby identifying the surgically curable forms of primary aldosteronism.

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

Adequate adrenal sampling is based on higher cortisol concentration compared with peripheral sampling. Dyna-CT and on-site quick cortisol assay could be helpful to improve the successful rate.

Cortisol hypersecretion is not uncommon condition in patients with PA. Conventional criteria for lateralization could be challenged due to underestimated lateralization index in AVS. Adjusted criteria should be considered.

AVS could be applied for lateralization of the adrenal gland with autonomous cortisol secretion and ACTH-independent Cushing’s syndrome.

The development of AVS relies on cooperation with teammates in Taiwan Primary Aldosteronism Investigation (TAIPAI) study group. We have gradually improved the performance on AVS that can be dedicated to the academic research.

71

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE3-3

UPDATE OF ADRENAL TUMORS: SURGERY OF ADRENAL TUMOR SHUO-MENG WANG Fu Jen Catholic University Hospital, Fu Jen Catholic University, Taiwan, R.O.C.

Technically there are two categories of recognized techniques by which a surgeon can remove an adrenal gland. Most small tumors can now be removed using minimally invasive techniques such as the posterior approach, or more frequently, the newly developed laparoscopic approach.

Open Surgical Techniques for Adrenalectomy with standard trans-Abdominal, thoraco-abdominal, posterior, or retroperitoneal approach. In large tumor (>10 cm) and tumors which are known to be malignant are almost never removed by minimally invasive operations, rather a more formal exploration and resection are required.

Laparoscopic Adrenalectomy. The laparoscopic approach for adrenal resection allows small to moderately sized tumors to be removed using scopes and very small incisions. This technique is tolerated very well and has been shown to have the least amount of postoperative pain and require the shortest hospital stay. This is now the preferred method for removal of small to moderate size adrenal tumors whether they produce hormones or not. Robotic-assisted laparoscopic adrenalectomy is an HPHUJLQJ PHWKRG WR DSSURDFK VRPH DGUHQDO JODQGV GLI¿FXOW WR EH DSSURDFKHG ZLWK SXUH ODSDURVFRSLF adrenalectomy method.

72

Abstract

SE4-1

THYROID & PREGNANCY HOSSEIN GHARIB, M.D., MACP, MACE Professor of Medicine, Mayo Clinic College of Medicine; Past President, American Association of Clinical Endocrinologists; Past President, American Thyroid Association

Thyroid function changes in pregnancy are many and profound. TSH remains the best thyroid test LQ SUHJQDQF\ DQG WULPHVWHU VSHFL¿F UDQJHV DUH DYDLODEOH ,RGLQH UHTXLUHPHQW LQFUHDVHV LQ SUHJQDQF\ and it is recommended that all women ingest 250 mcg iodine daily. Although universal screen is not suggested, thyroid testing should be considered for women with risk factors for pregnancy complications.

Management of subclinical hypothyroidism (SCH) is a matter of debate and it is not established that SCH adversely affects normal fetal neuro-psychologic development. Recent ATA guidelines HQGRUVH /7 WKHUDS\ LQ HDUO\ SUHJQDQF\ IRU 6&+ FRQVLGHULQJ LW ERWK VDIH DQG SRWHQWLDOO\ EHQH¿FLDO 3XEOLVKHG GDWD LV LQVXI¿FLHQW WR FOHDUO\ GHWHUPLQH LI /7 WKHUDS\ UHGXFHV SUHJQDQF\ ORVV LQ 732$E positive euthyroid women.

Serum TSH may be suppressed in up to 30% of normal pregnant women, often requiring no intervention. Gestational thyrotoxicosis is usually mild and transient, and can be treated with VXSSRUWLYH FDUH DQG IROORZ XS )RU V\PSWRPDWLF *UDYHV¶ GLVHDVH *' 378 LV WKH GUXJ LQ WKH ¿UVW trimester and methimazole for second & third trimesters. TSH & TT4 should be checked at 4 weeks and TT4/FT4 kept high-normal or just above-normal pregnancy range. In case of intolerance to ATD or poor thyroid control, thyroidectomy, best performed during the second trimester, is a good alternative.

The use of radioiodine is absolutely contraindicated in pregnancy.

Postpartum thyroiditis (PPT) includes hyper- or hypothyroidism during one year after delivery.

Commonly, hyper- is followed by hypothyroidism, with a return to a euthyroid state all within a few months. Symptomatic treatment with beta blockers is sometimes necessary. Of note, ATD use is safe for breastfeeding infants. While TRAb is negative in PPT, TPOAb is often positive and women with SRVLWLYH 732$E KDYH D VLJQL¿FDQWO\ KLJK ULVN RI UHFXUUHQW 337 ZLWK VXEVHTXHQW SUHJQDQFLHV

73

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE4-2

THYROID DISEASE AND LACTATION SHYANG-RONG SHIH Department of Internal Medicine, National Taiwan University School of Medicine; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital

Abnormal maternal thyroid status can impact milk letdown and the ability to successfully EUHDVWIHHG 0RWKHUV ZLWK PLOG WR PRGHUDWH K\SRWK\URLGLVP FRXOG H[SHULHQFH RQO\ PLQLPDO GLI¿FXOWLHV with breast feeding. As long as adequate nutrition, such as milk, is provided, maternal hypothyroidism itself is not harmful to the breast-feeding infant. Women experiencing poor lactation should have TSH measured. Subclinical and overt hypothyroidism should be treated in lactating women seeking to breastfeed.

Radioactive iodine is concentrated in breast milk. The use of 131I is contraindicated during lactation. The decision to treat hyperthyroidism in lactating women is guided by the same principles applied to non-lactating women. Low to moderate doses of propylthiouracil (PTU) and methimazole (MMI)/carbimazole are safe in breastfeeding infants. Maximal daily doses of 20mg MMI or 450mg PTU are suggested. The lowest effective dose of anti-thyroid drugs (ATDs) was advised. Growth and development should be monitored in breastfed children of women who are treated with ATDs. But routine assessment of the thyroid function in children is not recommended. $OO EUHDVW IHHGLQJ ZRPHQ VKRXOG LQJHVW DERXW ȝJ RI GLHWDU\ LRGLQH GDLO\ LQFOXGLQJ D GDLO\ RUDO VXSSOHPHQW FRQWDLQLQJ ȝJ RI LRGLQH 6XVWDLQHG LRGLQH LQWDNH PRUH WKDQ ȝJ GDLO\ should be avoided for the concern of inducing hypothyroidism in infants.

74

Abstract

SE4-3

THE INFLUENCE OF IODINE TO PREGNANT/NEONATE’S THYROID 1

C-J HUANG, 2F-F WANG

1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C. 2Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan, R.O.C.

Iodine is an essential micronutrient needed for thyroid hormone synthesis. It is especially important in pregnancy and early life due to its influence on brain development. Iodine deficiency OHDGV WR LRGLQH GH¿FLHQF\ GLVRUGHUV LQFOXGLQJ FUHWLQLVP LQFUHDVHG SUHJQDQF\ ORVV DQG LQIDQW PRUWDOLW\ intellectual impairments, growth retardation, and thyroid dysfunction with or without goiter. Cretinism and severe brain injuries are serious consequences of severe iodine deficiency during gestation; KRZHYHU HYHQ PLOG LRGLQH GH¿FLHQF\ LQ SUHJQDQF\ FDQ UHVXOW LQ OHVV IDYRUDEOH RXWFRPHV LPSDLULQJ children’s cognition, intelligence quotient, and school performances. In iodine-deficient regions, iodine supplementation to pregnant women has been shown to reduce cretinism, perinatal death, and infant mortality and improve the indexes of maternal thyroid function. Due to increased urinary iodine excretion during pregnancy and the fetal dependency on maternal iodine intake for thyroid hormone synthesis, the daily iodine requirement suggested by the World Health Organization (WHO) in pregnancy is 250 ȝJ SHU GD\ KLJKHU WKDQ WKH XVXDO GDLO\ UHTXLUHPHQW RI 150 ȝJ IRU DGXOWV Iodine insufficiency can lead to serious consequences as well as iodine over-nutrition in pregnancy. The American Thyroid Association (ATA) has recently lowered the tolerable upper intake level of iodine in pregnancy to 500 Pg per day, a level much less than the level of 1100 Pg for adults in JHQHUDO )RU QRUPDO DGXOWV OLYLQJ LQ LRGLQH VXI¿FLHQW UHJLRQV WKH WK\URLG LV VXEMHFWLYH WR SK\VLRORJLF adaptation to large amounts of iodine intake to prevent the occurrence of hyperthyroidism, namely the acute Wolff-Chaikoff effect. However, some individuals may have problem escaping from the acute Wolff-Chaikoff effect, rendering them susceptible to hypothyroidism under excessive iodine intake.

The fetus is especially vulnerable to large amounts of iodine because the ability to escape from the acute Wolff-Chaikoff effect does not mature until around 36 weeks of gestation. Long-term excessive iodine intake in pregnancy may lead to thyroid dysfunction, either hyper- or hypothyroidism. Prenatal iodine supplementation during gestation may be a simple, safe, and effective strategy to maintain optimal iodine status without causing under or over nutrition.

75

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE5-1

TREATMENT STRATEGY FOR PROLACTINOMA EUN JIG LEE, M.D., PH.D. President of Korean Endocrine Society, Professor of Endocrinology; Chairman, Department of Medicine; Yonsei University, College of Medicine; Chief Physician, Department of Medicine; Severance Hospital

A prolactinoma diagnosis is most likely to be made when serum prolactin levels are greater than 200 ng/ml. However, when serum prolactin levels are lower than 200 ng/ml and above normal range, a differential diagnosis should be considered, including intake of various medications, polycystic ovarian syndrome, hypothyroidism, chronic renal failure, severe head trauma, and non-functioning pituitary adenoma (NFPA), which may also compress the pituitary stalk and cause hyperprolactinemia.

Taken together, hyperprolactinemia with the existence of pituitary adenoma is consistent with prolactinoma; however, it is not a clear diagnosis of prolactinoma. Most patients with prolactinoma respond well to dopamine agonist (DA) therapy. DA therapy lowers serum prolactin levels and effectively reduces tumor size. However, although serum prolactin levels can be lowered by DA treatment in patients with NFPAs, a reduction of tumor size is not achieved in the majority of patients.

When hyperprolactinemic pituitary macroadenoma with serum prolactin levels lower than 200 ng/ml LV IRXQG PHGLFDO WUHDWPHQW FDQ EH ¿UVW FRQVLGHUHG 1)3$ RU GRSDPLQH UHVLVWDQFH LV VXVSHFWHG ZKHQ patients with hyperprolactinemic pituitary tumors do not respond to DA therapy. These patients require surgery. Determination of the timing of surgery is important because long-term use of DAs may cause ¿EURVLV DURXQG WKH WXPRU ZKLFK PDNHV WXPRU UHPRYDO PRUH GLI¿FXOW DQG LQFUHDVHV WKH ULVN RI DGYHUVH complications during the operative and post-operative periods, such as persistent hyperprolactinemia because of incomplete tumor excision and hypopituitarism because of damage to the normal gland.

In this session, we will discuss on optimized management of hyperprolactinemic pituitary tumors and also try to build an appropriate therapeutic strategy.

76

Abstract

SE5-2

THE 4TH EDITION (2017) OF WHO CLASSIFICATION OF PITUITARY TUMORS SHIH-CHIEH LIN Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital

The 4th edition of WHO classification of endocrine tumors had made several changes in the FODVVL¿FDWLRQ RI WXPRUV RI WKH SLWXLWDU\ JODQGV 7KHVH FKDQJHV LQFOXGH WKH IROORZLQJ (1)using transcription factors of pituitary adenohypophyseal cell lineages like PIT-1 (pituitaryVSHFL¿F 328 FODVV KRPHRGRPDLQ WUDQVFULSWLRQ IDFWRU 6) VWHURLGRJHQLF IDFWRU DQG WKH 7 3,7 7 ER[ IDPLO\ PHPEHU 7%; IRU FODVVL¿FDWLRQ RI SLWXLWDU\ QHXURHQGRFULQH WXPRUV (2)changes to the histological grading of pituitary neuroendocrine tumors with the elimination of “atypical adenoma”

LQWURGXFWLRQ RI QHZ HQWLWLHV OLNH WKH SLWXLWDU\ EODVWRPD DQG UHGH¿QLWLRQ RI ROG HQWLWLHV OLNH WKH null-cell adenoma (4)group of tumors arising in the posterior pituitary with thyroid transcription factor-1 (TTF-1) expression including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma 7KH QHZ FODVVL¿FDWLRQ LV SUDFWLFDO DQG LPPXQRKLVWRFKHPLVWU\ IRU SLWXLWDU\ KRUPRQHV SLWXLWDU\ VSHFL¿F WUDQVFULSWLRQ IDFWRUV DQG RWKHU LPPXQRKLVWRFKHPLFDO PDUNHUV FRPPRQO\ XVHG LQ SDWKRORJ\ SUDFWLFH DUH WKH PDLQ DQFLOODU\ GLDJQRVWLF WRRO 8OWUDVWUXFWXUDO DQDO\VLV LV QRW UHTXLUHG IRU FODVVL¿FDWLRQ of pituitary neuroendocrine tumors and only save for unusual tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas.

77

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE5-3

RECENT EVOLUTION OF ENDOSCOPIC ENDONASAL SURGERY FOR TREATMENT OF PITUITARY ADENOMAS S-H YANG Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.

Pituitary adenoma is a common intracranial tumor, accounting for 10-15% of all brain neoplasms.

Except prolactinoma, the first line treatment for symptomatic pituitary tumors is surgery. There are two approaches to reach the sellar region: transcranial and transsphenoidal. The first recorded pituitary surgery was performed in 1893. Initially in the early 20th century, transsphenoidal operation was favored by neurosurgeons for its less invasiveness, but later transcranial operation became the predominant approach for its superior exposure and clear surgical view. Following the introduction of VXUJLFDO PLFURVFRSH LQWR QHXURVXUJLFDO SUDFWLFH GXULQJ V WKH DPSOH LOOXPLQDWLRQ DQG PDJQL¿HG RSHUDWLYH ¿HOG XQGHU PLFURVFRSH PDGH WUDQVVSKHQRLGDO RSHUDWLRQ SRSXODU DJDLQ %HJLQQLQJ LQ V the use of endoscope further optimizes the surgical management of pituitary adenomas via the transsphenoidal route.

During surgery, endoscope enters from the nostril into the sphenoidal sinus. Televised video shows a panoramic view of pituitary fossa, as well as parasellar, suprasellar and infrasellar space. New JHQHUDWLRQ RI LPDJH V\VWHP QRZ SURYLGHV KLJK GH¿QLWLRQ RU HYHQ ' LPDJH (QGRVFRSH ZLWK GLIIHUHQW degrees of lens (0, 30, 45, 70 degrees) allows further visualization of the orbit, anterior skull base, pterygoid fossa, clivus, and craniocervical junction. Under endoscopic control, specially designed angled instruments facilitate dissection and resection of pituitary tumor from optic nerves, intracranial vessels and other critical neurovascular structures, which could only be reached in the past by the more invasive transcranial skull base approach. Because of these technical advancement, functional tumors like corticotroph and somatotroph adenoma can be removed along with a surrounding pseudocapsule to achieve higher rate of endocrine remission for patients with Cushing disease and acromegaly.

For nonfunctional tumors, complete tumor resection for optic nerve decompression is more likely, while the normal gland can be better visualized for preservation of pituitary function. Following tumor removal, reconstruction of sellar and skull base defect poses special challenge. A multi-layered reconstruction with nasoseptal flap, gasket seal/button graft, and synthetic tissue sealant drastically lowers the rate of CSF leakage. Finally, a surgical team consisting of neurosurgeon and ENT surgeon can fully exploit the advantages of endoscopic transsphenoidal surgery, especially for giant pituitary adenoma and other complex skull base lesions.

78

Abstract

SE6-1

RECENT UPDATE IN BASIC SCIENCE OF OSTEOPOROSIS WEI-YIH CHIU Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Wnt signaling plays an important role in development and maintenance of many organs and tissues, including bone. Although Wnt proteins signal through several pathways to regulate cell growth, GLIIHUHQWLDWLRQ IXQFWLRQ DQG GHDWK WKH :QW ȕ FDWHQLQ SDWKZD\ DSSHDUV WR EH SDUWLFXODUO\ LPSRUWDQW IRU ERQH ELRORJ\ 7KH :QW ȕ FDWHQLQ VLJQDOLQJ SDWKZD\ LV FRPSOH[ DQG FRQVLVWV RI QXPHURXV UHFHSWRUV inhibitors, activators, modulators, phosphatases, kinases and other components. However, the protein ȕ FDWHQLQ LV WKH FHQWUDO WDUJHW DQG DQ HVVHQWLDO FRPSRQHQW RI WKH :QW ȕ FDWHQLQ VLJQDOLQJ SDWKZD\ While there are several receptors (low-density lipoprotein receptor–related proteins), and over twenty activators known as the Wnts, and several inhibitors such as sclerostin, dickkopf and secreted frizzledUHODWHG SURWHLQ WKHVH DOO WDUJHW ȕ FDWHQLQ 7KH VXEMHFW RI WKLV VSHHFK ZLOO EH WKH LQWHUDFWLRQ RI ȕ FDWHQLQ with different factors and the role of this pathway in bone development and function.

79

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE6-2

UPDATE IN EPIDEMIOLOGY AND DIAGNOSIS OF OSTEOPOROSIS JAWL-SHAN HWANG, MD Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

Osteoporosis is a major public health problem in many countries, as well as in Taiwan. It’s the most common metabolic bone disorder, characterized by a decrease in bone mass and deterioration in skeletal microarchitecture, which lead to increased fragility and susceptibility to fractures. The fractures associated with osteoporosis have been proven to cause considerable disability, loss of quality of life and mortality. Patients who have one osteoporotic fracture are at increased risk for having another osteoporotic fracture develop. The risk of fragility fractures is multifactorial and is related to the strength of bone, and non-skeletal factors contributing to the incidence and impact of trauma. It is increasing in prevalence and remains largely underdiagnosed and undertreated in Taiwan.

In epidemiology study for women and men aged 65 years old and over, 19.8% and 12.5%, respectively, had more than one vertebral fracture in Taiwan, and estimated that 30% of postmenopausal women had osteoporosis based on bone mineral density. The National Nutrition Survey in Taiwan reported that for men and women over the age of 50, the prevalence of osteoporosis was 23.9% and 38.3%, respectively. From the 1996-2002 NHI data, overall incidence of hip fractures in those individuals over 65 years of age had increased from 496 to 644 per 100,000 per year. It is HVWLPDWHG WKDW DSSUR[LPDWHO\ RQH WKLUG RI ZRPHQ DQG RQH ¿IWK RI PHQ LQ WKHLU OLIHWLPH ZRXOG KDYH at least one osteoporosis associated fractures. The mortality rate of hip fractures in the elderly within the first year for women and men is about 15% and 22%, respectively. However, 2006-2007 NHI data showed that only 27% of hip fracture patients received BMD examinations, and 34% received drug treatment of osteoporosis. Many patients were not given the opportunity to have appropriate osteoporosis assessments and not being treated. The awareness of osteoporosis management among patients and physicians clearly needs to be improved.

Osteoporosis diagnosis includes low-impact fractures made via clinical history. The most common sites of bone fractures include distal forearm, hip, or vertebrae (compression fracture).

Clinically, it is possible to screen for osteoporosis by a physical examination. However, X-ray or BMD PHDVXUHG E\ GXHO HQHUJ\ GHQVLWRPHWU\ ';$ LV QHHGHG WR EH DUUDQJHG WR FRQ¿UP VXFK D GLDJQRVLV 2VWHRSRURVLV LV GLDJQRVHG DFFRUGLQJ WR WKH 7 VFRUH GHULYHG IURP %0' 7KH FODVVL¿FDWLRQV DUH QRUPDO 7 ORZ ERQH PDVV 7 EHWZHHQ DQG 2VWHRSRURVLV 7

80

Abstract

SE6-3

RECENT ADVANCES IN PHARMACEUTICAL TREATMENT OF OSTEOPOROSIS ጿջང ᇄτᚃଲϲऌഌІሊ‫ݎ‬ຩ‫ܛ‬

Denosumab and bisphosphonates are the most commonly used antiresorptive drugs in Taiwan.

Denosumab has been proven to be effective and safe up to 10 years. A recent concern is the multiple vertebra fracture and rapid bone loss after discontinuation. Probably shifting to another antiresorptive, such as a bisphosphonate is necessary. A recent study showed that for osteopenic postmenopausal women, infusion of zolendronic acid every 18 months for 6 years resulted in effective increase of bone density and reduction of bone fracture incidence. Furthermore, cancer incidence of all cause mortality was also reduced.

The only currently available bone forming agent in Taiwan is teriparetide. It is a potent drug for osteoporosis, and has been proven to have no additive effect if given at same time with bisphosphorals.

However, a recent series of studies showed that combined use of teriparatide and denosumab rersulted in additive increases of bone density, yet the antifracture data is not available.

The concept of treat-to-target is based on the analysis that after bone density recovered upto a FHUWDLQ OHYHO WKH IUDFWXUH UDWH ZRXOG GHFUHDVH VLJQL¿FDQWO\ ZKLOH IXUWKHU LQFUHDVH RI ERQH GHQVLW\ LV accompanies by a small further reduction of fracture risk only. It must be aware that after reaching this target, if no medication is used, there would be a rapid bone loss and increase of bone fracture rate. Enen after the so called drug holiday for bisphophontes, fracture risk would increase gradually if the patient is left untreated. Long term management plan thus is appropriate for all the osteoporotic patients.

81

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE7-1

THYROID RADIOFREQUENCY ABLATION: PAST PRESENT AND FUTURE JUNG HWAN BAEK, M.D., PH.D. Professor of Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; President of the Korean Society of Thyroid Radiology

Ultrasound (US)-guided ablations such as radiofrequency ablation (RFA), laser ablation (LA), ethanol ablation (EA), microwave ablation (MWA) and high intensity focused ultrasound (HIFU) ablation have been used to treat benign thyroid nodules, recurrent thyroid cancers and even primary thyroid microcarcinoma.

Korean Society of Thyroid Radiology (KSThR) introduced first recommendation in 2012 and we revised it 2018. The basic and advanced concept of thyroid RFA have been established throughout PDQ\ UHVHDUFKHV DQG ZHOO GRFXPHQWHG LQ WKLV UHYLVHG WK\URLG 5)$ JXLGHOLQH ,Q RWKHU VFLHQWL¿F JURXSV they recently introduced their opinion about thyroid RFA. In this review, I will introduce the basic concept of thermal ablations focusing on the thyroid RFA and explain the development of the procedures. Furthermore, I will show the current status of thyroid 5)$ LQ .RUHD DQG RWKHU DUHDV $QG ¿QDOO\ , ZLOO SURSRVH WKH IXWXUH RI WKLV SURPLVLQJ SURFHGXUH LQ RXU thyroid practice.

82

Abstract

SE7-2

RFA IN THYROID DISEASES: THE VIEW OF ENDOCRINOLOGIST IN TAIWAN a

MING-TSANG LEE, M.D., b*CHIH-YUAN WANG , M.D., PH.D.

a

Division of Endocrinology, Department of Internal Medicine, Far-Eastern Memorial Hospital, Taipei, Taiwan Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

b*

Radiofrequency ablation (RFA) is a minimally invasive technique, used with ultrasound or computed tomography guidance, which can produce tissue coagulation necrosis in various kinds of tumors in the human body. In the past ten years, more and more studies about radiofrequency ablation in benign thyroid nodules have been published. Reviewing these studies, we noticed that the effectiveness of ablation was higher when it was performed with the “moving-shot technique“ via an internally cooled electrode. A consensus statement published from the Korean Society of Radiology also suggested the “moving-shot technique“ as a standard ablation procedure for benign thyroid nodule ablation in Korea. In Taiwan, most symptomatic benign nodules are currently treated with surgical removal. Radiofrequency ablation for mass lesions is primarily performed for the treatment of metastatic hepatic tumors. In our case, we have attempted to introduce radiofrequency ablation for benign thyroid nodules to Taiwan. Because endocrinologists in Taiwan were not familiar with this technique, we adopted a stepwise approach in learning how to perform radiofrequency ablation. We conducted ex vivo animal ablation exercises to gain experience in setting the radiofrequency generator for the right ablation mode and appropriate power output. The thyroid nodule volume reduction rate after 1-year of follow-up was about 50% in this case. The most important thing we learned from this WULDO LV WKDW ZH FRQ¿UPHG WKH VDIHW\ RI WK\URLG QRGXOH DEODWLRQ 7R WKH EHVW RI RXU NQRZOHGJH WKLV LV WKH ¿UVW UHSRUWHG VWXG\ RI UDGLRIUHTXHQF\ DEODWLRQ RI D WK\URLG QRGXOH LQ 7DLZDQ

83

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE7-3

THE DEVELOPMENT OF RFA OF THYROID DISEASE: TECHNIQUE AND PATENT IN TAIWAN W-H HSIEH, H-H LU Bio-IT Technology Division, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Taiwan, R.O.C.

OBJECTIVE: Radiofrequency ablation (RFA) has been adopted as a minimally invasive therapy in treating the early liver cancers to achieve the curative outcome and been also reported to be safe and effective for treating benign thyroid nodules. Currently the commercial RFA systems in Taiwan are all imported from other countries. The development of the RFA system in Taiwan was investigated so as to learn the current status and its applications on the treatment of thyroid nodules.

METHOD: We searched for the patents of intellectual property office and technology development programs of Ministry of Economic Affairs (MOEA) with the keywords of “ablation” and/ or “thyroid”. The results related to the RFA were collected and the associated apparatus and methods were analyzed.

RESULT: Industrial Technology Research Institute (ITRI) recently developed a RFA system ZLWK HOHFWULFDO VSHFL¿FDWLRQV DQG WKH DEODWLRQ RXWFRPH FRPSDUDEOH WR WKH &RRO WLS V\VWHP RI &RYLGLHQ e.g. output power of up to 200W, internal cooling, temperature monitoring, and impedance control algorithm. Metal Industries Research & Development Centre (MIRDC), on the other hand, developed a percutaneous electromagnetic thermablate system. The major application of both systems is for the liver tumors. ITRI, however, developed an image guide apparatus and needle electrodes for the RFA of thyroid nodules.

CONCLUSION: In summary, research institutes in Taiwan showed the capability of developing the RFA system and the accessories for treating thyroid nodules, while the major application of RFA seems remain for treating liver tumors.

84

Abstract

YL-1

HEME-DERIVED BILINS: NEW THERAPEUTICS FOR INFLAMMATORY DISEASES JON Y. TAKEMOTO, PH.D. Professor of Biology; Department of Biology, Utah State University

In mammals, heme-derived bilins are most often associated with red blood cell destruction and hemoglobin degradation in the spleen and skin bruises. Bilins result from cleavage of heme by the enzyme heme oxygenase to generate biliverdin, bilirubin, and other bilins that are eventually eliminated in bile, feces and urine. The overall process reduces levels of heme which is toxic when accumulated. Bilins also occur - often in abundance - in microbes, plants and other animals where they play many roles. Discoveries of new and diverse roles for bilins are emerging such as sensing and JDWKHULQJ OLJKW UHJXODWLQJ JURZWK DQG DJLQJ DQG F\WRSURWHFWLRQ DJDLQVW LQIHFWLRQ DQG LQÀDPPDWLRQ and bilins are being explored for beneficial uses in medicine and agriculture. Most prominent is biliverdin which has protective effects against several diseases and inflammatory conditions.

Discussed will be the experimental therapeutic effects of biliverdin (including against diabetes) in animal models, the discovery of its bilin analog mesobiliverdin, and cytoprotection by these bilins of pancreatic islets in islet transplantation procedures.

85

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

YL-2

INVESTIGATION OF THE CAUSES AND MANAGEMENT OF NONALCOHOLIC FATTY LIVER DISEASES P-J HSIAO Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University, Taiwan, R.O.C

Non-alcoholic fatty liver disease (NAFLD), first described in 1980, is defined by the accumulation of hepatic fat (triglyceride) more than 5% without other recognized cause of fatty liver, e.g., alcohol, virus, drugs, autoimmunity or inherited disease. It is rapidly becoming the most common cause of chronic liver diseases, and is the second-most common indication for liver transplantation in the world. The global prevalence of NAFLD is estimated 25% and 3-18% in pediatric population. NAFLD is regarded to be the hepatic manifestation of metabolic syndrome with comorbidities with obesity (51.3%), type 2 diabetes (22.5%), hyperlipidemia (69.2%), hypertension (39.3%) and metabolic syndrome (42.5%). From simple steatosis, NAFLD may progress and worsen to nonalcoholic steatohepatitis (NASH, 30-40%) and further progress to cirrhosis (40-50%) and/or to hepatocellular hepatoma (HCC, 7%) within 10 years. The major risk factors for progression are well established, e.g., age > 50 yrs, obesity, insulin resistance, T2DM, increased ferritin, and PNPLA3 (1148M) polymorphism. The growing evidence has demonstrated NAFLD is a multisystem disease with an important burden of extra-hepatic chronic complications, such as metabolic syndrome, atherosclerosis cardiovascular disease (CVD), higher myocardial fat, cardiac arrhythmia, chronic kidney disease (CKD) and colon cancer. Cardiovascular disease is the leading cause of mortality in NAFLD patients, followed by non-hepatic malignancy and liver-related death (liver cirrhosis or hepatocellular carcinoma).

Pathophysiology of the hepatic fat accumulation originates from the “ectopic fat accumulation”, when positive energy imbalance has occurred with lipid accumulation besides adipose tissue. It is associated with increased diabetogenic hepatokines (retinol binding protein (RBP4), fibroblastic growth factor (FGF)-21) or inflammatory biomarkers (e.g., CRP, TNF-a, IL-6) to enhance gluconeogenesis, decrease glycogen synthesis and inhibit insulin signaling. Increasing evidence also suggests that dysbiosis of the gut microbiota plays a key role to regulate the intrahepatic metabolism DQG LQÀDPPDWLRQ DQG OHDGV WR WKH GHYHORSPHQW RI 1$)/' 7KH DGLSRVH WLVVXH G\VIXQFWLRQ LV DOVR D NH\ FRQWULEXWRU WR WKH SDWKRJHQHVLV RI 1$)/' ZLWK LQFUHDVHG IDWW\ DFLG LQÀX[ FDXVLQJ KHSDWLF OLSLG DFFXPXODWLRQ LQÀDPPDWLRQ DQG LQVXOLQ UHVLVWDQFH 7KHUH LV VWLOO ODFN RI VSHFL¿F DQG HIIHFWLYH SKDUPDFRORJLF WKHUDS\ WR PDQDJH WKH RFFXUUHQFH DQG progression of NAFLD. All the guideline has advocated with lifestyle intervention for NAFLD, such as Mediterranean diet, aerobic exercise, resistance training to target weight loss 7-10%. The potential 86

Abstract

drugs are widely discordant by the guidelines, such as metformin, pioglitazone, Vitamin E, silymarin, GLP-1 analogues and statins, etc. Effective weight loss by bariatric surgery has successfully resolved RI KHSDWLF VWHDWRVLV DQG RI VWHDWRKHSDWLWLV EXW ZRUVHQ VLJQL¿FDQWO\ WKH KHSDWLF ¿EURVLV LQ years but with higher mortality. Because co-existing comorbidities is the progression or fatal cause of NAFLD, treatment strategy should focus the co-morbidities and lie on the management of the “insulin resistance” related metabolic syndrome but not NAFLD itself.

87

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

YL-3

INVESTIGATING THE ROLE OF GLUCOCORTICOID-HEPASSOCIN PATHWAY IN THE HIGH-FAT DIET-INDUCED OBESITY-RELATED METABOLIC DISORDERS 1

H-C HUNG, 2Y-M KUO

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital. 2Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University

OBJECTIVE 6RFLDO GHIHDW VWUHVV DJJUDYDWHV WKH KLJK IDW GLHW +)' LQGXFHG PHWDEROLF GH¿FLWV High levels of glucocorticoids, the primary stress hormone, play a critical role in the development of obesity. However, the role of the HFD-induced increment of corticosterone level in the HFD-induced metabolic disorders remains unclear.

METHODS We employed adrenalectomy in male C57BL/6 mice and subjected a transgenic C57BL/6-Cyp11a1tm2Bcc/Narl (L/L) mice which has normal basal corticosterone level but a blunted corticosterone response to stress stimuli to address this question.

RESULTS A 12-week HFD regimen induced obesity, impaired glucose metabolism, and elevated the circulating level of corticosterone in male C57BL/6 mice. Bilateral adrenalectomy attenuated the HFD-induced adipose expansion, hepatic steatosis and insulin resistance without affecting the food intake amounts in mice. The adrenalectomized mice had higher blood triglyceride level than the sham control mice after the 12-week HFD treatment. The preadipocyte marker, preadipocyte factor 1 (Pref-1), decreased in the epididymal white adipose tissue in the HFD mice but was restored by adrenalectomy. Re-supplementing corticosterone to the adrenalectomized mice abolished this adrenalectomy-induced effect on the Pref-1 level in the white adipose tissue. The L/L mice had lower peripheral expression of corticosterone than the wild-type mice after a 12-week HFD regimen. HFDinduced obesity and adipose expansion were milder in the L/L mice than those in the wild-type ones.

Compared to the wild-type-HFD mice, the L/L-HFD mice had higher circulating triglyceride level and Pref-1 expression in the white adipose tissue.

CONCLUSIONS HFD-induced increase of corticosterone is essential for the adipogenesis during the process of HFD-induced adipose expansion.

88

Abstract

YL-4

THE RELATIONSHIP BETWEEN SERUM ANGPTL6 AND INCIDENT DIABETES IN HUMAN – FOLLOW UP STUDY 1

H-Y LI

1

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

Type 2 diabetes mellitus is one of the most prevalent chronic diseases in the world and could lead to multiple complications to the patients such as cardiovascular disease, neuropathy, nephropathy and retinopathy. Recently, liver is found to secrete various hepatokines to regulate energy homeostasis and glucose metabolism, which is similar to the concept of adipokines. Angiopoietin-like 6 (ANGPTL6) is a novel hepatokine which increases energy consumption, lower body weight and improve insulin sensitivity, as shown by animal studies. In 2015, we analyze the relationship between serum ANGPTL6 and the incidence of diabetes in a longitudinal cohort, using the grant from the Diabetes Association of R.O.C. We found that high serum ANGPTL6 is associated with a lower incidence of diabetes, adjusted for age, gender, family history of diabetes, body mass index, and hemoglobin A1c, which is LQ FRQFRUGDQFH ZLWK WKH ¿QGLQJV IURP DQLPDO VWXGLHV +RZHYHU FURVV VHFWLRQDO DQDO\VLV XVLQJ GDWD DW baseline in our cohort reveals that plasma ANGPTL6 is higher in subjects with pre-diabetes, compared with that in normal controls. Similarly, cross-sectional studies in the literature showed that serum ANGPTL6 were higher in subjects with diabetes than in healthy subjects.

We believed that hyperglycemia can stimulate serum ANGPTL6 secretion to maintain glucose homeostasis, which can be used to explain the results from cross-sectional studies. In the present study, we explored the changes of serum ANGPTL6 level after acute hyperglycemia in humans. Besides, we investigated regulation and function of ANGPTL6 in glucose metabolism in hepatic cell and rodent models.

By using the data and materials from the cohort study, we measured serum ANGPTL6 concentrations during 75g oral glucose tolerance tests (OGTT), including samples collected at fasting, 30-min and 120-min after OGTT. The result showed that serum ANGPTL6 increased after glucose challenge. Serum ANGPTL6 concentration at 120-minutes after 75gm OGTT was significantly higher than fasting serum ANGPTL6 concentration (p < 0.001). Besides, fasting serum ANGPTL6 concentration was positively associated with serum ANGPTL6 concentration at 30-minutes after glucose challenge (r = 0.5833, p < 0.0001), serum ANGPTL6 concentration at 120-minutes after glucose challenge (r = 0.05873, p < 0.0001) and area under the curve of serum ANGPTL6 FRQFHQWUDWLRQ GXULQJ DQ 2*77 U S 7KHVH ¿QGLQJV VXJJHVWHG WKDW IDVWLQJ VHUXP ANGPTL6 is positively associated with the response of serum ANGPTL6 to hyperglycemia.

We also conducted animal and cell studies to explore the regulation and function of ANGPTL6.

89

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Firstly, we analyze the plasma ANGPTL6 protein in mice fed a normal diet (ND) or a high-fat diet (HFD) since 8 weeks for a period of 12 weeks (n = 6) by Western blot and ELISA. Immunoblotting revealed more abundant ANGPTL6 expression in mice fed with a high-fat diet than in a normal diet.

3ODVPD $1*37/ SURWHLQ ZDV DOVR VLJQL¿FDQWO\ KLJKHU LQ KLJK IDW GLHW PLFH WKDQ QRUPDO GLHW PLFH S < 0.05). Secondly, we validated that if ANGPTL6 could protect from advancer glycated end-products (AGE)-induced hepatocyte death. The HepG2 cells were pre-treated with ANGPTL6 recombinant protein for 3 hours and then treated with 3 mM methylglyoxal for another 18 hours. The cell viability

by MTT assay revealed that ANGPTL6 dose-dependently protected from AGE-induced hepatocyte death.

In conclusion, serum ANGPTL6 increased in response to hyperglycemia in humans and mice, which could be useful to maintian glucose homeostasis and to protect hepatocytes from hyperglycemiainduced injury.

90

Abstract

OD1

CLINICAL PREDICTIVE FACTORS FOR ALL-CAUSE MORTALITY AND RENAL FUNCTION DETERIORATION IN TYPE2 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 CHIPIN-PING CHEN, SZU-TAH CHEN, CHUNG-HUEI HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan, R.O.C.

To explore the factors predicting all-cause mortality and renal function deterioration in Type2 diabetic patients with chronic kidney disease stage 3(CKD3). METHODS: We collected 850 Type2 diabetic patients who joined in shared care with CKD3 from 2010 January 1 to December 31, 2017.

The prospective cohort data from the north medical center, and the deadline of the follow-up was December 31, 2017. Survival analysis was performed by Kaplan- Meier method. Cox proportional hazards regression model was used to assess the all- cause mortality after adjustment for confounding factors. RESULTS: The average age of the subjects was 68.27 ± 10.20 years. During the seven-years follow-up period, 66 (7.8%) patients dialysis and 130(15.3%) patients died. Results of Cox regression model showed thatthe progression of dialysis risk in the Type 2 diabetic patients with CKD3 were the EDVHOLQH H*)5 +5 &, WKH ¿UVW \HDU GHFOLQH H*)5 +5 &, 1.15), CKD3duration (HR = 1.11, 95% CI:1.00-1.24), age (HR = 0.97, 95% CI:0.94-0.99) and baseline retinopathy (HR = 2.39, 95% CI:1.14-5.01).The all-cause mortality risk in the Type 2 diabetic patients with CKD3werethe second year decline eGFR (HR = 1.03, 95% CI:1.01-1.06), and age (HR = 1.09, 95% CI:1.06-1.123).CONCLUSION: We should focus on the prevention and treatment of the Type 2 diabetic patients with CKD3in order to attenuate progression of renal dysfunction and mortality.

91

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD2

SERUM RIBONUCLEASE L AS A FIRST-TRIMESTER BIOMARKER FOR PREDICTION OF GESTATIONAL DIABETES MELLITUS 1

YI-TING WANG, 2SHIN-YU LIN, 3WEI-SHIUNG YANG

1

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University; 2Department of Obstetrics and Gynecology, National Taiwan University Hospital; 3Department of Internal Medicine, National Taiwan University Hospital

Background: *HVWDWLRQDO GLDEHWHV PHOOLWXV *'0 LV D FRPPRQ PHWDEROLF FRPSOLFDWLRQ GH¿QHG by glucose intolerance during pregnancy. Ribonuclease L (RNase-L) was considered as a ubiquitous enzyme involved in various cellular functions such as innate immunity and adipogenesis. Moreover, serum RNase-L was found to be negatively associated with human blood glucose level in our previous study. The aim of this study is to evaluate the association between serum RNase-L level and the risk for GDM. Methods: 87 pregnant women were recruited in this study. For GDM diagnosis, the participants have received a one-step 75-g oral glucose tolerance test (OGTT) between 24-28 weeks of pregnancy in accordance with the International Association of the Diabetes and Pregnancy Study Group. Binary logistic regression analysis was used to estimate the association between GDM risk and the serum RNase-L levels in three trimesters of pregnancy with the adjustment of age, body mass index, medical KLVWRU\ DQG WKH ¿UVW WULPHVWHU IDVWLQJ JOXFRVH OHYHO 5HFHLYHU RSHUDWLQJ FKDUDFWHULVWLF 52& DQDO\VLV was used in the GDM predictive model of serum RNase-L. Results: The serum RNase-L levels of pregnant women tended to descend with gestational age (P for trend = 0.001). The pregnant women with GDM had lower serum RNase-L level than those ZLWKRXW *'0 LQ JHVWDWLRQ ¿UVW WULPHVWHU YV ȝJ PO 3 VHFRQG WULPHVWHU YV ȝJ PO 3 WKLUG WULPHVWHU YV ȝJ PO 3

7KH ¿UVW DQG VHFRQG WULPHVWHU VHUXP 51DVH / OHYHOV ZHUH LQYHUVHO\ DVVRFLDWHG ZLWK WKH ULVN RI *'0 ¿UVW WULPHVWHU RGGV UDWLR 25 FRQ¿GHQFH LQWHUYDO &, 3 VHFRQG trimester: OR = 0.77, 95% CI:0.62-0.97, P = 0.026). The area under the ROC curves of the serum 51DVH / YDOXHV LQ WKH ¿UVW WULPHVWHU ZDV IRU *'0 &, 3

Conclusions: The serum RNase-L level as a novel early biomarker for GDM was inversely DVVRFLDWHG ZLWK *'0 ULVN LQ WKH ¿UVW WULPHVWHU RI SUHJQDQF\

92

Abstract

OD3

THE EFFICACY OF HIGH-FREQUENCY EXTERNAL MUSCLE STIMULATION FOR SYMPTOMATIC PERIPHERAL NEUROPATHY IN PATIENTS WITH TYPE 2 DIABETES 1

JUI-HUNG CHEN, 1, 2YI-JEN HUNG, 3SU-CHEN WANG, 3CHIEH-HUA LU, 3 CHANG-HSUN HSIEH, 3CHIEN-HSING LEE 1

Division of Endocrinology and Metabolism, Tri-Service General Hospital Songshan branch, National Defense Medical Center, Taipei, Taiwan, ROC; 2Division of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC; 3Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

Background: Diabetic distal symmetric sensory polyneuropathy (DSP) approximately accounts for 20-30% patients with type 2 diabetes in Taiwan. While the etiology of DSP in diabetes is not well understood, symptomatic treatment using pharmacological therapies is often less effective. Noninvasive, non-pharmacological therapy of high-frequency external muscle stimulation has been useful for management of DSP in Caucasian diabetic patients. However, it is still unknown in Asian SRSXODWLRQ :H GHVLJQHG D VWXG\ WR HYDOXDWH WKH HI¿FDF\ RI KLJK IUHTXHQF\ H[WHUQDO PXVFOH VWLPXODWLRQ (hfEMS) for symptomatic peripheral neuropathy in patients with type 2 diabetes in Taiwan.

Methods: Thirty adult patients with type 2 diabetes complicated with DSP and symptom questionnaire of pain or numbness more than score 3 (score range from 1 to 10) were enrolled. Each patient received an hfEMS device (HITOP 191, gbo-Medizintechnik AG, Rimbach/Germany) for 60 min twice per week for 12 weeks. Symptom questionnaires were evaluated at baseline, 6-week and 12week. Blood metabolic parameters were also determined.

Results: 11 male and 19 female with mean age of 65.7 years were enrolled. After 12-week treatment, the symptoms of formication, burning, pain and numbness sensations of low limbs were VLJQL¿FDQWO\ DOOHYLDWHG DOO 3 'LVWXUEDQFH RI VOHHS DQG PXVFOH FUDPS SDLQ ZHUH DOVR LPSURYHG (P < 0.001). However, body weight, blood pressure and blood metabolic parameters including fasting JOXFRVH $ F OLSLG SUR¿OHV ZHUH QRW VLJQL¿FDQWO\ FKDQJHG Conclusions: Non-invasive hfEMS may provide a useful tool for ameliorating the neuropathic symptoms in patients with type 2 diabetes in Asian population.

93

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD4

MACHINE LEARNING APPROACH TO PREDICT LONG-TERM MORTALITY FOR DIABETIC INPATIENTS 1

YU-HSUAN LI, 2YUNG-CHUN CHANG, 1I-TE LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Graduate Insititute of Data Science, Taipei Medical University

2

Background: Inpatients with diabetes have higher mortality than those without, and a variety of adverse outcomes has been observed after their discharge. Although several traditional predictors have EHHQ LGHQWL¿HG LQ SUHYLRXV VWXGLHV DQ HIIHFWLYH SUHGLFWLRQ PRGHO IRU ORQJ WHUP PRUWDOLW\ LV ODFNLQJ Methods: Diabetic patients who admitted due to a primary diagnosis of poor glucose control between 1996 and 2007 were included in this study. Clinical data during hospitalization were collected for analyses. The mortality data were obtained from registry in Taiwan. We applied support vector PDFKLQH 690 ZKLFK LV D VXSHUYLVHG OHDUQLQJ PHWKRG ZLOGO\ XVHG LQ FODVVL¿FDWLRQ SUREOHP WR SUHGLFW ORQJ WHUP PRUWDOLW\ ,Q RUGHU WR LQYHVWLJDWH WKH HI¿FLHQF\ RI IDFWRU ZH IXUWKHU DGRSW XQLYDULDWH IHDWXUH selection approach to seek for the best combination of features. To derive credible evaluation results, we utilize the 10-fold cross validation method on the dataset. The evaluation metrics are the accuracy and receiver operating characteristic (ROC) curve.

Results: A comprehensive performance evaluation of the proposed approach with other methods is provided. A total of 1214 patients were included for analysis. During a median of 6.7 years follow up, 641 patients died. The results demonstrated that our proposed method utilizes the top 20 percentile selected features (i.e. follow up time, age, chronic kidney disease status, diabetic duration, diabetic retinopathy, and history of hypertension) could achieve a remarkable performances with 78% accuracy.

ROC curve showed an area under the curve of 0.824.

Conclusions: Prediction of long-term mortality for diabetic inpatients is an important and widely studied task in smart healthcare. To this end, we proposed a supervised learning approach for detection of long-term mortality. We also utilized feature selection method to explore different features, and ¿QDOO\ ZH SLFN RXW YDOXDEOH IDFWRUV WKH\ DUH IROORZ XS WLPH DJH FKURQLF NLGQH\ GLVHDVH VWDWXV diabetic duration, diabetic retinopathy, and history of hypertension.

94

Abstract

OD5

THE INFLUENCE OF MEAN HBA1C ON THE ASSOCIATION OF HBA1C VARIABILITY WITH ALL-CAUSE MORTALITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1

CHING-CHU CHEN, 1CHWEN-TZUEI CHANG, 2KUO-CHIN HUANG, 1 RONG-HSHING CHEN, 1TZU-YUAN WANG, 1KUEI-MEI YEH, 1CHI-YU HUANG, 1 JUEI-YU TSENG, 1MAO-TSU FUH 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; 2Integration of Traditional Chinese-Western Medicine, Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.

BACKGROUND: HbA1c variation had been reported to be related with mortality in patients with type 2 diabetes mellitus (T2DM) but the effect of mean HbA1c on this relationship in different variability status is unclear. We aimed to evaluate the effect of mean HbA1c on this relationship in both low and high variation status in patients with T2DM. METHODS: Enrollees with T2DM, age of diabetes onset 30 years or greater, at least three measurements of HbA1c were included. HbA1c variability score, HbA1c-CV and HbA1c-SD were analyzed by quartile. HbA1c variability score 50 was used as a cut point to define low and high glycemic variability.

RESULTS: $ WRWDO RI VXEMHFWV ZHUH LGHQWL¿HG RI ZKRP GLHG GXULQJ WKH years observation period. The all-cause mortality increased with quartile of HbA1c variability score, HbA1c-CV and HbA1c-SD. The associated strength attenuated after an adjustment for mean HbA1c.

The associated risk was similar between variability status and glycemic control status. The highest DVVRFLDWHG ULVN ZDV +E$ F YDULDELOLW\ VFRUH ! SOXV PHDQ +E$ F 0HDQ +E$ F OHYHO 6.0% was associated with a higher mortality risk in both low and high glycemic variability status. The DVVRFLDWHG ULVN RI PRUWDOLW\ ZDV VLJQL¿FDQW ZKHQ PHDQ +E$ F ! DQG ! LQ ORZ DQG KLJK glycemic variation status, respectively.

CONCLUSIONS: HbA1c variation independently associated with all-cause mortality in a trend manner. Mean HbA1c contributed to this relationship. A J-distribution of men HbA1c related to the mortality in both low and high variation status.

95

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD6

ELECTRONEGATIVE LDL OF PEOPLE WITH METABOLIC SYNDROME INDUCES ATHEROGENESIS VIA DISRUPTION OF STRA6 CASCADE 1

CHAO-HUNG CHEN, 2LIANG-YIN KE, 2CHIH-SHENG CHU, 2HUA-CHEN CHAN, 4 TATSUYA SAWAMURA, 3CHIA-WEI LAI, 5CHU-HUANG CHEN, 3SHYI-JANG SHIN 1

Graduate Institute of Medicine, Kaohsiung Medical University; 2Lipid Science and Aging Research Center, Kaohsiung Medical University; 3Divison of Endocrinology and Metabolism, KMU Hospital; 4Department of Physiology, School of Medicine, Shinshu University, Japan;5Vascular and Medical Research, Texas Heart Institute, Houston, TX, USA.

Background: Electronegative LDL(L5) is the most atherogenic fraction of LDL and is elevated in people with metabolic syndrome (MetS). RBP-4 receptor (STRA6) cascade is disrupted in a few organs of obesity-related diseases. Our objective is to investigate whether L5 from people with MetS capably induces atherosclerosis through the disruption of STRA6 cascade.

Methods: We examined the in vivo and in vitro effects of L5 on STRA6 cascade and atherosclerosis in mice and vascular cells. To investigate the role of STRA6 cascade on atherosclerotic formation, crbp1 transfection was performed in vitro.

Results: KLV VWXG\ VKRZV WKDW / DFWLYDWHV DWKHURJHQLF PDUNHUV S 0$3. 7*)ȕ 6PDG DQG 003 DQG VLPXOWDQHRXVO\ VXSSUHVVHV 675$ VLJQDOV 675$ &5%3 /5$7 5$5Į DQG 5;5Į

in aortas of L5-injected mice and L5-treated aortic endothelial and smooth muscle cells. These L5induced changes of STRA6 cascade and atherogenic markers were reversed in aortas of LOX1-/mice and in LOX1 RNA silenced-vascular cells. Furthermore, crbp1 gene transfection reversed the disruption of STRA6 cascade and the increase of atherogenic pathway in L5-treated cells.

Conclusions: This study reveals that L5 from people with MetS induces atherosclerosis by disrupting STRA6 signaling pathway. Suppression of STRA6 may be one novel pathway of atherosclerosis in people with MetS.

96

Abstract

OE1

DIAGNOSTIC VALUE OF ADRENAL I-131 NP-59 SCINTIGRAPHY FOR PRIMARY ALDOSTERONISM: A RETROSPECTIVE STUDY AT A MEDICAL CENTER IN NORTH TAIWAN 1

WU MING-HSIEN, 1 LIU FENG-HSUAN, 2 LIN KUN-JU, 1 SUN JUI-HUNG, 1 CHEN SZU-TAH 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan.; 2Molecular Imaging Center and Department of Nuclear Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan, Taiwan

Background: Primary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are: bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of I-131 1,6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish PA from APA. Methods: Patients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 post-unilateral adrenalectomy and 7 post-radiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal VFLQWLJUDSK\ SULRU WR VXUJHU\ 7KH DFFXUDF\ RI WKH 13 DGUHQDO VFLQWLJUDSK\ ZDV FRQ¿UPHG E\ WKH SDWKRORJLF ¿QGLQJV DQG SRVWRSHUDWLYH RXWFRPHV Results: Among 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and 7 bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3%, 44.4% and 92.3%, respectively. Moreover, SPECT/CT scan increased WKH VHQVLWLYLW\ DQG VSHFL¿FLW\ EXW QRW WKH SRVLWLYH SUHGLFWLYH YDOXH DQG RI 13 59 scintigraphy in this study.

Conclusions: NP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

97

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE2

HYPERTHYROIDISM IS ASSOCIATED WITH HOSPITALIZATION FOR SEPSIS: A NATIONWIDE POPULATION-BASED STUDY 1

LI-HSIN CHANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, Taiwan

Background: Hyperthyroidism is a common endocrine dysfunction with systemic adverse effects in cardiovascular and skeletal system but the association with hospitalization for sepsis has not been studied. The purpose of this study is to demonstrate the association between hyperthyroidism and hospitalization for sepsis.

Methods: The population-based cohort study using data from 1996 to 2012 in the Taiwan National Health Insurance Research Database was conducted. A total of 5761 hyperthyroidism were identified and majority with age and gender fit the characters of Graves’ disease. 57610 controls matched by the propensity score were retrieved. The events of hospitalization for sepsis and outcomes after hospitalization were compared between two groups.

Results: )LYH KXQGUHG DQG VL[W\ ¿YH HYHQWV RFFXUUHG LQ JURXS RI K\SHUWK\URLGLVP DQG WKH HYHQWV rate was higher than control group (incidence rate 9.8% versus 8.8%, p = 0.002 by log-rank test).

Subjects with hyperthyroidism were associated with higher risk of hospitalization for sepsis even after adjusting with all baseline characters (HR 1.18, 95% CIs 1.08-1.29, p < 0.001). The results were consistent in different infective sources and all subgroups. Patients with hyperthyroidism had lower inhospital mortality and hemodialysis rate when sepsis occurred.

Conclusions: Hyperthyroidism increases risk of hospitalization for sepsis but not worsens inhospital outcomes when sepsis occurs.

98

Abstract

OE3

FACTORS PREDICTING ABNORMAL LIVER FUNCTION TESTS INDUCED BY HYPERTHYROIDISM CHING JUNG HSIEH Department of Internal Medicine, Paochien Hospital, Ping Tung, Taiwan

Background: Abnormal liver function tests (LFTs) are often found in patients with hyperthyroidism. The interaction between the thyroid and liver is for maintaining homeostasis in both organs. Thyroid hormones are glucuronidated and sulfated within the liver and subsequently excreted into bile. Thyroid hormones also could maintain the metabolism of bilirubin. There are few data demonstrating the factors or biochemical factors contributing to LFT abnormalities. The aim of this study was to investigate predicting factors for abnormal LFTs induced by hyperthyroidism.

Methods: Single-institution retrospective cohort study. 3DWLHQWV \HDUV ROG UHFHLYLQJ PHGLFDO care at a regional hospital between January 2009 to December 2017.

Inclusion criteria were a serum thyroid stimulating hormone [TSH] concentration 1.48 ng/ dL. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin. Serum levels of anti-thyroid peroxidase (anti-TPO) antibody, TSH receptor antibody (TRAb) were also recorded. All patients were divided into abnormal LFTs (group A) and normal LFTs (group B). Logistic regression analysis was used to determine predictive factors contributing to abnormal LFTs. Results: There were 519 consecutive cases of newly diagnosed and untreated patients.

The overall incidence of any biochemical liver test abnormality within 6 months of hyperthyroidism was 17.9%. The frequencies of ALT, AST and TBIL abnormalities were 52.7%, 21.5%, 65.6%, respectively. In the univariate analysis, patients in group A had significantly higher FT4 concentration (3.44 vs 2.34 ng/dL, P = 0.004) and TRAb (28.9 vs 19.5 IU/L, P = 0.001) when compared with those in group B. Logistic regression analysis revealed higher FT4 levels, higher TRAb value and male gender to be independent risk predicting factors.

Conclusions: 7KLV VWXG\ LGHQWL¿HV ULVN IDFWRUV IRU SDWLHQWV ZKR GHYHORS DQ DEQRUPDO VHUXP OLYHU biochemical test result within 6 months of the diagnosis of new-onset untreated hyperthyroidism.

99

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE4

SEX DIFFERENCES IN ANDROGEN RECEPTOR ARE RELATED TO TUMORIGENESIS OF HUMAN PAPILLARY THYROID CARCINOMA 1

CHEN-KAI CHOU, 2SHUN-YU CHI, 3HONG-YO KANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C; 2Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C; 3Graduate institute of Clinical medicine science, Chang Gung University, Taiwan, R.O.C

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, accounting for ~80% of all thyroid cancers. Gender variation in the incidence of thyroid cancer is well known, more women than men are diagnosed with the disease at a ratio of 3–5.5:1. While females have an increased incidence of thyroid tumors, males have a high rate of malignancy with poor prognosis.

The aim of this study is to determine the role of Androgen receptor (AR) in PTC’s tumorigenesis.

Methods: The expression levels of AR of 116 PTC surgical specimens and its adjacent normal thyroid specimens from Kaohsiung Chang Gung Memorial hospital were assessed via quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). The association of clinical risk factors and AR expression were also analyzed.

Results: We noticed the majority of PTC specimens, both in male and female group exhibited lower AR expression level as compared to the normal thyroid tissues. Furthermore, the expression RI $5 LQ PDOH QRUPDO WK\URLG WLVVXH ZDV VLJQL¿FDQWO\ KLJKHU WKDQ IHPDOH QRUPDO WK\URLG WLVVXH 2Q WKH FRQWUDU\ QR VLJQL¿FDQW H[SUHVVLRQ GLIIHUHQFH LQ GLIIHUHQW JHQGHU 37& VDPSOHV )XUWKHUPRUH :H also notice those with higher cancer stage and extra-thyroidal extension had significant lower AR H[SUHVVLRQ FRPSDUHG WR WKRVH FODVVL¿HG ZLWK ORZ ULVN JURXS S YDOXH

Conclusions: These results highlight the importance of AR in PTC’s development and tumorigenesis, which may suggest the protective role of AR in PTC. Key word: Papillary thyroid carcinoma: Androgen receptor

100

Abstract

OE5

IODINE NUTRITIONAL STATUS OF PREGNANT WOMEN IN AN URBAN AREA OF NORTHERN TAIWAN WITH HIGH PREVALENCE OF PRENATAL MULTIVITAMIN INTAKE 1

CHI-LUNG TSENG, 2CHANG-CHING YEH, 3CHEN-CHANG YANG, 4FAN-FEN WANG, 5 CHUN-JUI HUANG 1

Division of Gastroenterology, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2Department of Obstetrics & Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; 3Division of Clinical Toxicology & Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan; 5Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Pregnant women has long been considered one of the most vulnerable group for LRGLQH GH¿FLHQF\ 3UHYLRXV QXWULWLRQDO VXUYH\ UHYHDOHG WKDW WKH PHGLXP XULQDU\ LRGLQH FRQFHQWUDWLRQ 8,& IRU ZRPHQ DW FKLOG EHDULQJ DJH RI \HDUV LQ 7DLZDQ ZDV ȝJ / ZKLFK LV LQVXI¿FLHQW IRU pregnant women. However, the actual iodine nutritional status in pregnancy is unknown.

Design: 7KH SULPDU\ REMHFWLYH RI WKLV VWXG\ ZDV WR UHSRUW IRU WKH ¿UVW WLPH WKH LRGLQH QXWULWLRQDO status of pregnant women in Taiwan. In addition, dietary sources of iodine nutrition were investigated.

A hospital-based cross-sectional survey of pregnant women was conducted in Taipei Veterans General Hospital in 2018. UIC was determined by inductively coupled plasma mass-spectrometry. A food frequency questionnaire was delivered.

Result: 7KH PHGLDQ 8,& ZDV ȝJ / ZKLFK VXJJHVWHG VXI¿FLHQW LRGLQH QXWULWLRQ 7KH PRVW frequently consumed iodine-containing foods were dairy products. The use of iodine-containing dietary supplements was common (51.5% of the women consume multivitamins especially designed for pregnancy every day). The questionnaire also revealed that 42.3% of the women were unaware of the salt product (iodized or not) in their households.

Conclusion: The results indicate that the iodine status in pregnant women in Northern Taiwan is adequate. The difference in median UIC in pregnant women and women at child-bearing age generally may be related to the common use of iodine-supplement during pregnancy.

101

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE6

THERAPEUTIC PLASMA EXCHANGE IN THYROID STORM 1

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

1

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

Background: Thyroid storm is an extreme manifestation of thyrotoxicosis with high mortality if inadequately treated. Agranulocytosis, a rare side effect of antithyroid drugs, poses further challenges WR WKH EULGJLQJ WKHUDS\ WRZDUG GH¿QLWLYH VXUJLFDO WUHDWPHQW +HUH ZH SUHVHQW WKH FDVH RI D SDWLHQW LQ which plasmapheresis was used preoperatively to treat thyroid storm complicated with agranulocytosis.

Case: A 57-year-old woman presented to the emergency department with fever, dyspnea, and sore throat. She was diagnosed with Graves’ disease 6 years prior and was treated with methimazole from then on, stopped for 3 months but resumed for 2 weeks by herself for progressive dyspnea and thyroid HQODUJHPHQW (.* VKRZHG DWULDO ¿EULOODWLRQ ZLWK UDSLG YHQWULFXODU UHVSRQVH /DERUDWRU\ GDWD UHYHDOHG bicytopenia (WBC 1100/cumm, platelet 19000/cumm) and direct hyperbilirubinemia (total bilirubin 3.82 mg/dL) in addition to elevated troponin-I, undetectable TSH, and elevated free T4 > 5 ng/dL. Lugol’s solution was administered after one dose of propylthiouracil but discontinued both on the next day due to development of agranulocytosis (WBC 400/cumm, ANC 224/cumm). Plasmapheresis was started to control thyrotoxicosis. After 3 sessions of plasmapheresis, thyroid hormone levels decreased to normal range (free T3 2.2 pg/mL, free T4 0.86 ng/dL). 12 days later she received a total thyroidectomy uneventfully. She was subsequently discharged with levothyroxine replacement.

Follow-up visit showed resolution of bicytopenia and hyperbilirubinemia.

Conclusions: Plasmapheresis has been used in the treatment of hyperthyroidism since 1970.

While its role has not been established in the treatment of thyroid storm, prompt initiation of SODVPDSKHUHVLV FDQ EH OLIH VDYLQJ IRU SDWLHQWV LQ ZKLFK ¿UVW OLQH WKHUDS\ IDLOHG RU LV FRQWUDLQGLFDWHG

102

Abstract

AP-1

THE DIVERSIFIED ROLE OF LIVER FAT AND HEPATOKINES IN METABOLIC DISEASES HORNG-YIH OU Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Taiwan.

Metabolic diseases such as obesity, diabetes, and cardiovascular diseases are increasingly public health issues in modern society. The accumulation of ectopic fat plays an important role in the pathogenesis of these diseases. During the past years, my research interest has been focused on the diverse roles of liver fat accumulation (fatty liver) and hormones secreted by liver (hepatokines) in metabolic diseases.

In this talk, I will first present our researches on the hepatokines, fetuin-A. We found hyperglycemia-related endoplasmic reticulum stress induced the expression of fetuin-A to develop insulin resistance. In humans, serum fetuin-A concentrations are elevated in impaired glucose tolerance and newly-diagnosed type 2 diabetes, and the presence of NAFLD significantly increases fetuin-A levels in normoglycemia and prediabetes. Both diabetes and fetuin-A are independently associated with increased risk of arterial stiffness. Furthmore, pharmacologic treatment with a selective G proteincoupled receptor 40 agonist, GW-9508, decreases the hepatic expression of fetuin-A to improve insulin sensitivity and hepatic steatosis in diabetic mice.

Then, I will discuss another hepatokine, hepassocin. We found that subjects with NAFLD and prediabetes/diabetes have a higher serum hepassocin level than those without it. Overexpression of hepassocin induces hepatic steatois and steatohepatitis through an ERK1/2-dependent pathway.

Hepassocin also induces insulin resitance in mice model. Furtheromore, in subjects with hyperlgycemic crisis, we demonstrated that increased hepassocin secretion might offset the deleterious effects of hyperglycemia on hepatocytes.

Finally, I will show our collaborative work with NTUH on fatty liver and fatty pancreas. We found the prevalence of fatty pancreas is high in the general population. Both diabetes and NAFLD are important independent associated factors of fatty pancreas. With an increase in glycemia, a VLJQL¿FDQWO\ JUHDWHU SURSRUWLRQ RI VXEMHFWV KDV 1$)/' DQG IDWW\ SDQFUHDV ,QWHUHVWLQJO\ ERWK 1$)/' and fatty pancreas are associated with diabetes independent of age, gender, adiposity, and other cardiometabolic risk factors.

Taken together, our research suggests that hepatokines play an important role in the development of fatty liver, pathogenesis of insulin resistance and arterial stiffness, and protection from hyperglycemia-related hepatic injury. In addition, fatty liver and fatty pancreas have a synergistic effect in the pathogenesis of diabetes.

103

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-2

GENETIC VARIATION OF SORBS1 GENE IS ASSOCAITED WITH GLUCOSE HOMEOSTASIS AND AGE AT ONSET OF DIABETES: A SAPPHIRE COHORT STUDY CHANG TJ1, WANG WC2,3, HSIUNG CA3, HE CT4, LIN MW5,6, SHEU WHH7,8,9, CHANG YC1,10,11 48(57(50286 712, CHEN YDI13, ROTTER JI13,14, CHUANG LM1,15 & SAPPHIRE STUDY GROUP* 1

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 2The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. 3Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. 4Department of Endocrinology and Metabolism, Tri-Service General Hospital, Taipei, Taiwan. 5Institute of Public Health, National Yang-Ming University, Taipei, Taiwan. 6Department of Medical Research & Education, Taipei Veterans General Hospital, Taipei, Taiwan.

7 Department of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan.

8 School of Medicine, National Yang-Ming University, Taipei, Taiwan. 9School of Medicine, National Defense Medical Center, Taipei, Taiwan. 10Graduate Institute of Medical Genomics and Proteomics, National Taiwan University Medical College, Taipei, Taiwan. 11Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan. 12Division of Cardiovascular Medicine, Falk CVRC, Stanford University School of Medicine, Stanford, CA, USA. 13Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. 14Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA. 15Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

16 Section of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan. 17Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. 18Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. 19Department of Social Work, Tunghai University, Taichung, Taiwan. 20School of Medicine, Chung Shan Medical University, Taichung, Taiwan. * The SAPPHIREe Study Group: Hwu CM16,17, Hung YJ4,9, Lee WJ18,19, Lee IT7,8,20

Purpose: The SORBS1 gene plays an important role in insulin signaling. We aimed to examine whether common single-nucleotide polymorphisms (SNPs) of SORBS1 are associated with prevalence and incidence of diabetes, age at onset of diabetes, and the related traits of glucose homeostasis.

Method: A total of 1135 siblings from 492 ethnic Chinese families were recruited at baseline, and 630 were followed up for 5.19 ± 0.96 years. Nine SNPs including rs7081076, rs2281939, rs3818540, rs2274490, rs61739184, rs726176, rs2296966, rs17849148, and rs3193970 were genotyped and examined. To deal with correlated data of subjects within the same families, the generalized estimating equations approach was applied throughout all association analyses.

Result: The GG genotype of rs2281939 was associated with a higher risk of diabetes at baseline, an earlier onset of diabetes, and higher steady-state plasma glucose levels in the modified insulin suppression test. The minor allele T of rs2296966 was associated with higher prevalence and incidence of diabetes, an earlier onset of diabetes, and higher 2-h glucose during oral glucose tolerance test.

104

Abstract

These two SNPs revealed independent associations with age of diabetes onset as well as risk of diabetes at baseline.

Conclusion: These findings supported that SORBS1 gene participates in the pathogenesis of diabetes.

105

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-3

TRANSCRIPTOME ANALYSIS OF PAPILLARY THYROID CANCER HARBORING TELEMERASE REVERSE TRANSCRIPTASE PROMOTER MUTATION 1

M-N CHIEN, 2P-S YANG, 3Y-C HSU, 2,4T-P LIU, 2,5J-J LEE, 2,5S-P CHENG

1

Division of 1Endocrinology and Metabolism, Department of Internal Medicine, 2Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan. 3Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan. 4Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan. 5Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Purpose: Telomerase reverse transcriptase (TERT) promoter mutations have recently been LGHQWL¿HG DV DQ LPSRUWDQW SURJQRVWLF IDFWRU LQ WK\URLG FDQFHU 6WXGLHV VXJJHVW WKDW 7(57 PD\ KDYH noncanonical functions beyond telomere maintenance.

Method: Clinicopathological information and transcriptome data for papillary thyroid carcinoma (PTC) samples were obtained from The Cancer Genome Atlas (TCGA). Propensity score matching was performed to adjust for potential confounding variables between the TERT promoter wild-type group and the mutant group. Gene expression data of 36 patients in the mutant group were systemically compared to those of 72 patients in the wild-type group.

Result: Tumors with TERT promoter mutations had a higher TERT expression. Pathways central WR '1$ GDPDJH UHVSRQVHV DQG FHOO F\FOH UHJXODWLRQ ZHUH VLJQL¿FDQWO\ HQULFKHG DPRQJ XSUHJXODWHG genes. Transporter and metabolic activities were overrepresented among 799 downregulated genes.

There was no difference in the expression of most of the thyroid differentiation genes.

Conclusion: The TERT promoter mutations were associated with proliferative and metabolic alterations in PTC.

106

Abstract

PD01

THE ASSOCIATION OF GLYCEMIC VARIABILITY IN T2DM PATIENTS RECEIVING BASAL OR PREMIXED INSULIN MANAGEMENT CHIA-FEN WANG, WAN-CHI CHUANG, WEI-CHENG CHANG, CHIH-HSUN CHU Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. ROC.

Background: This study aims to demonstrate whether premixed insulin, compared to basal insulin (combined with OAD), could provide a superior improvement of glycemic variability (assessed

by CGMS) and a better improvement of CIMT in T2DM patients.

Methods: The study conducted with 38 type 2 diabetic patients receiving insulin management (19 with basal insulin, 19 with premixed insulin). The patients are from the outpatient clinic of Endocrinology/Metabolism in Kaohsiung Veterans hospital. The inclusion criteria were aged 20 80 years who has been diagnosed with T2DM. Treatment with basal (combined with OAD), or premixed insulin for more than 1 year. The HbA1c levels were between 6.5 % to 10.0 %. The exclusion FULWHULD ZHUH SDWLHQWV ZLWK W\SH '0 JHVWDWLRQDO RU DQ\ RWKHU VSHFL¿F W\SH RI '0 ,Q DOO VXEMHFWV biochemistries were analyses, CGM and CIMT were performed.

Results: The age, gender and duration of diabetes were not different. The total insulin dose were 25 ± 16 vs 70 ± 45 units (basal vs premixed insulin). The patients with basal insulin took more OAD than those with premixed insulin. The levels of HbA1c were also not different. (basal vs premixed insulin: 8.6 ± 1.0 vs 8.4 ± 0.9%, p = 0.598). In comparison of the parameters of glucose variability (MAGE, SD, time above range, time in range, time below range, AUC above limit, AUC below limit) EHWZHHQ ERWK JURXSV WKHUH ZHUH QR VLJQL¿FDQW GLIIHUHQFH 0RUHRYHU ERWK JURXSV DOVR VKRZHG VDPH value of mean CIMT (basal vs premixed insulin: 0.69 ± 0.12 vs 0.72 ± 0.11mm, p = 0.492). The multivariate linear regression analysis for determining the factors of mean CIMT showed that only age is related to it.

Conclusions: Premixed insulin cannot get less glucose variability than basal insulin in T2DM patient. Moreover, premixed insulin seemed have no beneficial effect in atherosclerotic change measured by CIMT.

107

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD02

PARTICIPATION IN DIABETES SHARED-CARE NETWORK BENEFICIAL FOR DEPRESSION AND GLYCEMIC CONTROL AMONG DM SUBJECTS 1

PEI-LING TSAI, 2WEI-PIN CHANG, 3PI-YUAN WONG, 3I-CHUAN LIN, 3I-JU LIEN, 3 JIUN-YIAN LIN, 3TONG-YUAN TAI 1

Department of Clinical Laboratory, Taipei Jen-Chi Hospital, Taiwan, R.O.C; 2School of Health Care Administration, Taipei Medical University; 3Department of Internal Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C

Background: Diabetes mellitus (DM) and depression are closely related as depression may lead to DM, and DM patients are more susceptible to depression. After the establishment of DM sharedFDUH QHWZRUN LQ PRUWDOLW\ UDWH RI '0 KDV EHHQ GHFOLQLQJ 7KH VWXG\ DLPHG WR DVVHVV WKH LQÀXHQFH of joining a DM shared-care network on depression alleviation and to explore the factors which may relate to the occurrence of depression among DM patients.

Methods: Based on purposive sampling, the study recruited 95 diabetics recently participating in the DM shared- care network hosted by a community hospital in north Taiwan. Data concerning the gender, age, body weight, body height, BMI, marital status, living condition (alone or not), DM duration, DM family history, smoking status, and DM medication of each subject were recorded. The study used the Chinese version of the 18-item Clinically Useful Depression Outcome Scale (CUDOS) with a 4-point Likert scale whose total score ranges from 0-72. Depression was diagnosed if the score read DQG KLJKHU VFRUHV LQGLFDWHG JUHDWHU VHYHULW\ RI GHSUHVVLRQ 7KH UHFUXLWHG VXEMHFWV FRPSOHWHG WKH CUDOS questionnaire both upon recruitment (i.e. early stage of their participation in the DM sharedcare network) and six months after recruitment. They also received blood tests for glucose, HbA1c, cholesterol, triglyceride, HDL-C, LDL-C, creatinine, and GPT levels. Independent t-test, paired t-test, one-way ANOVA, Pearson product-moment correlation, and multiple logistic regression methods were XVHG IRU VWDWLVWLFDO DQDO\VHV 3 WDLOHG ZDV FRQVLGHUHG VLJQL¿FDQW Results: VXEMHFWV RU VFRUHG RQ &8'26 'HSUHVVLRQ HPHUJHG WR EH QHJDWLYHO\ correlated with age (r = -0.255, p < .05). Solitary-living subjects (t = 2.109, p < .05) and divorced subjects (F = 3.082, p < .05) appeared to be more likely to suffer from depression. Results of multiple logistic regression analysis on demographic and clinical characteristics further revealed that solitaryliving subjects (OR = 5.8, p < .05) and divorced subjects (OR = 4.034, p < .05) were more vulnerable to depression. Differences in the following four items upon recruitment and six months after UHFUXLWPHQW UHDFKHG VLJQL¿FDQFH &8'26 VFRUH W S +E$ F W S *37 (t = 2.150, p < .05), and HDL-C (t = -2.765, p < .05).

Conclusions: Participation in a DM shared-care network, as the study suggests, helps improve depression, as well as glycemic control, liver function, and HDL-C, among diabetics. Younger age is 108

Abstract

associated with a higher CUDOS score, and DM patients living alone or divorced appear to be more susceptible to depression.

109

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD03

HEMOCHROMATOSIS PRESENTING AS DIABETES MELLITUS: A CASE REPORT 1

YU-TZU LIN, 2YI-SUN YANG, 2CHIEN-NING HUANG

1

Department of Nursing, Chung-Shan Medical University Hospital, Taiwan; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taiwan

Hemochromatosis is common genetic disorder of Caucasians characterized by iron overload syndrome with enhanced intestinal absorption of iron associated with potential iron overload in peripheral tissues presenting with complications as cirrhosis, hepatocellular carcinoma, diabetes mellitus, and heart diseases. However, it is relative rare in Asians. We present a case in a 48-year-old male presented with generalized weakness, easy fatigability, loss of weight, and loss of concentration/ interest in routine work for 6 months. Diabetes mellitus was diagnosed and started with oral antidiabetic drugs. However, persisted weight loss despite of glycemic improvement warrants for further evaluation. No history of blood transfusion or jaundice noted. Family history was insignificant.

Physical examination revealed hepatomegaly, and mild splenomegaly. Ultrasound and magnetic resonance imaging showed hepatomegaly with nodular margin, hypertrophied caudate lobe, and hypointensity suggesting cirrhosis of liver associated with hemochromatosis. The ferritin level was ȝJ / $ SURYLVLRQDO FOLQLFDO GLDJQRVLV RI GLDEHWHV ZLWK FLUUKRVLV RI OLYHU DQG SUREDEO\ ZLWK hemochromatosis was made. The whole hereditary hemochromatosis genome was sequenced but failed to localize any genetic alterations. The patient was treated with phlebotomy for several times, ferritin level returned to normal. For glycemic control, he is receiving basal insulin and oral-antidiabetic drugs. About 50% cases diagnosed with hemochromatosis will have type 1 or 2 diabetes. The likelihood of hemochromatosis in the adult population of diabetic patients is reportedly between 1% and 2%. Sometimes, diabetes is the only apparent manifestation of hemochromatosis in unrecognized cases. Clinicians should be aware that hemochromatosis may occur in Taiwan population with variable iron overload and should be recognized/diagnosed early for prompt therapy and prevent complication/ premature death.

110

Abstract

PD04

INTERFERENCE OF HEMOGLOBIN VARIANT J-BANGKOK ON GLYCATED HEMOGLOBIN (HBA1C) MEASUREMENT - A CASE REPORT 1

CHUN-CHUNG LIN, 1HAO-CHANG HUNG, 1KAI-PI CHENG, 1RU-LAI HUANG, 1 HORNG-YIH OU 1

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

HbA1c is a stander marker to evaluate glycemic control in patients with diabetes mellitus.

However, there are clinical conditions interfering the accuracy of HbA1c, which may lead to misestimate the glycemic status. It depends on physician’s awareness of discordance between glucose level and HbA1c value. Here, we report a case with hemoglobin variant (Hb J-Bangkok) interferences HbA1c measurement.

A 42-year-old man was diagnosed diabetes mellitus in 2009, and he received medical control with metformin 1500mg per day since 2010. The patient had ST elevation myocardial infarction of inferior wall on 2018/01/09 and underwent percutaneous coronary intervention. The HbA1c and fasting plasma glucose was 7.6% and 199mg/dL, respectly. He was prescribed with three kinds of oral antidiabetic drugs (metformin 1500mg, glimepiride 4mg, and sitagliptin 100mg) and long acting insulin (Glargine) 40 unit per day due to his hyperglycemic status while admission. Three months later, the HbA1c value was 4.4%, and fasting plasma glucose was 100mg/dL, and there was no hypoglycemia event. And his self-monitoring of blood glucose (SMBG) of fasting glucose was about 90-110 mg/dL. Hemoglobin electrophoresis revealed Hb J-Bangkok 42.9%, then he received empagliflozin and metformin for diabetes control. Three months later, the HbA1c value was 4.6%, and fasting plasma glucose was 97mg/dL. When discordance between HbA1c and plasma glucose level, conditions interfering the accuracy of HbA1c, such as hemoglobinopathy should be suspected.

111

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD05

DIABETIC KETOACIDOSIS ASSOCIATED WITH INCREASED LEVEL OF LITHIUM CONCENTRATION - A CASE REPORT 1

TZU-CHIEN LIN, 2YE-FONG DU, 2CHING-HAN LIN, 2HORNG-YIH OU

1

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

A 52-year-old woman treated with lithium (1050-1,200 mg/day) for bipolar disorder since 2009 was observed of first hyperglycemia episode on 2014/06/28 with random glucose 400 mg/dl when admitted to psychiatric ward for mania with psychotic features. After regular insulin 6U subcutaneous injected once, no more hyperglycemia was noted in subsequent one month. Lithium level reached 1.05mmol/L on 2014/07/01 which is the highest level ever in her record. No anti-diabetic agent was initiated after that episode. However, she was admitted to our hospital again on 2014/08/13 due to fever with diabetic ketoacidosis and hyperglycemia hyperosmolar syndrome. Serum glucose was 591 mg/dL with positive serum and urine ketones. Lithium level reached 1.10mmol/L, which is the highest level ever. After insulin infusion and hydration, she recovered quickly. Her hyperglycemia was controlled with Novomix 28U TID/AC sc after discharge. Besides, lithium was discontinued and VKLIWHG WR 4XHWLDSLQH ,QVXOLQ UHTXLUHPHQWV GHFUHDVHG UDSLGO\ LQ PRQWKV DQG ZDV VKLIWHG WR PHWIRUPLQ 500mg bid and sitagliptin 100mg qd at 6th month follow-up with optimal blood glucose control.

There’s no hyperglycemic emergencies episode during four years of subsequent follow-up.

We suggested increased level of lithium may be associated with her diabetic ketoacidosis even when her lithium level is still controlled within optimal therapeutic range. Physician should pay attention to the potential hyperglycemia effect induced by high normal lithium concentration.

112

Abstract

PD06

0,5 $77(18$7(6 */8&2/,3272;,&,7< ,1'8&(' Ǻ &(// DYSFUNCTION AND APOPTOSIS VIA INSULIN SIGNALING 1

HSIN-HUA LI, 1CHIH-LI LIN LIN, 2CHIUNG-HUEI PENG, 3EDY KORNELIUS, 3 YI-SUN YANG, 1YI-CHIAO BAI, 1HSIAO-LI HO, 1CHIEN-YIN KUO, 3CHIEN-NING HUANG 1

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Department of Nursing, Hungkuang University, Taichung, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

Background: %RWK LQVXOLQ UHVLVWDQFH DQG SDQFUHDWLF ȕ FHOO G\VIXQFWLRQ DUH WZR FULWLFDO GHWHUPLQDQWV IRU W\SH GLDEHWHV 7 ' SDWKRJHQHVLV 3DUWLFXODUO\ D FRQWLQXRXVO\ ȕ FHOO G\VIXQFWLRQ OHDGLQJ WR DSRSWRVLV SUHFHGHV ȕ FHOO H[KDXVWLRQ RYHU WLPH +RZHYHU WKH NH\ WR DWWHQXDWH ȕ FHOO dysfunction still remains largely unknown. The clinical drug glucagon-like peptide-1 (GLP-1) receptor DJRQLVW DQG GLSHSWLG\O SHSWLGDVH '33 LQKLELWRUV ZHUH REVHUYHG SUHYHQWLQJ ȕ FHOO G\VIXQFWLRQ apoptosis, and proliferation in vivo. But the exact mechanism remains unclear.

Methods: Many studies have demonstrated that several microRNAs (miRNAs) contribute to the pathogenesis of T2D. Particularly, we have previously demonstrated that upregulation of miR-302 is able to alleviate insulin resistance by activation of Nanog. In addition, miR-302 also demonstrated anti-oxidative stress activities that plays a crucial role in the slowing the aging process, suggesting PL5 PD\ H[HUW SRWHQWLDO EHQH¿WV LQ SUHYHQWLQJ PHWDEROLF GLVRUGHUV VXFK DV 7 ' +RZHYHU WKH GHWDLOHG PROHFXODU PHFKDQLVPV XQGHUO\LQJ PL5 LQ ȕ FHOO SURWHFWLRQ DUH VWLOO ODUJHO\ XQFOHDU :H DLPHG DW WKH SURWHFWLYH PHFKDQLVP RI PL5 FRQWULEXWHV WR 7 ' SDWKRJHQHVLV LQ ȕ FHOO G\VIXQFWLRQ Results: In the present study, we investigated the mechanisms of miR-302 against JOXFROLSRWR[LFLW\ LQGXFHG ȕ FHOO G\VIXQFWLRQ DQG DSRSWRVLV 2XU UHVXOWV VKRZHG WKDW JOXFROLSRWR[LFLW\ LQGXFHG ȕ FHOO DSRSWRVLV GHFUHDVHG DFWLYDWLRQ RI $NW LQFUHDVHG DFWLYDWLRQ RI 067 DQG LQKLELWHG WKH downstream signaling. However, upregulation of miR-302 displayed protective effect by attenuating ȕ FHOO G\VIXQFWLRQ DQG DSRSWRVLV WKURXJK UHVWRUDWLRQ RI LQVXOLQ VLJQDOLQJ SDWKZD\ Conclusions: We expect these results can provide details of miR-302 at molecular basis involved LQ WKH SDWKRJHQHVLV RI 7 ' $FFRUGLQJO\ UHVWRUDWLRQ RI ȕ FHOO IXQFWLRQ E\ WDUJHWLQJ PL5 UHODWHG mechanisms may demonstrate potential implications to develop novel preventive, diagnostic, or therapeutic strategies in slowing disease progression of T2D.

113

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD07

LIRAGLUTIDE ATTENUATES FREE FATTY ACID-INDUCED LIPOTOXICITY AND INSULIN RESISTANCE IN C2C12 MYOTUBES 1

HSIN-HUA LI, 1CHIH-LI LIN LIN, 2CHIUNG-HUEI PENG, 1YI-CHIAO BAI, 1 HSIAO-LI HO, 1CHIEN-YIN KUO, 3YI-SUN YANG, 3EDY KORNELIUS, 3 CHIEN-NING HUANG 1

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Department of Nursing, Hungkuang University, Taichung, Taiwan ; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

Background: The prevalence of obesity-related diabetes and metabolic disorder has increased dramatically over the past 20 years. Particularly, T2D is a chronic disease characterized by disruption in the metabolism of glucose and lipids, and consequential failure in the production of insulin and insulin resistance. These dysfunctions are due in part to ineffective treatment of blood glucose and lipids by peripheral tissues such as fat and muscle tissue. The abnormal lipid dynamics are caused by increased free fatty acid (FFA) flux and thereby induces insulin resistance. Particularly, chronic elevation in plasma FFA levels is commonly associated with impaired insulin-mediated glucose uptake in skeletal muscles. Although the precise mechanism of FFAs-induced lipotoxicity involved in the development of muscle insulin resistance remains unknown yet, there are not available the effective treatments for obesity-related disorder.

Methods: Recently studies indicated that glucagon-like peptide-1 (GLP-1) increases basal energy expenditure, curtails weight gain, and inhibits the development of insulin resistance, diabetes, and hepatic steatosis. Liraglutide, a GLP-1 receptor agonist, is an analogue of human incretin binding to the same receptors as does the endogenous metabolic hormone GLP-1 and stimulates insulin secretion.

However, the protective effects of liraglutide involved in FFA-induced lipotoxicity have not yet been investigated. Here, we aimed the protective effect of liraglutide against FFA-induced lipotoxicity and insulin resistance in C2C12 myotube.

Results: Our results showed that the treatment of FFA in C2C12 myotube increased lipid droplet, R[LGDWLYH VWUHVV DQG LPSDLUV LQVXOLQ VLJQDOLQJ &RQYHUVHO\ OLUDJOXWLGH VLJQL¿FDQWO\ SURWHFWHG DJDLQVW FFA-induced lipotoxicity and oxidative stress by restoring insulin downstream signaling.

Conclusions: 2XU ¿QGLQJV VXJJHVW OLUDJOXWLGH FDQ UHVWRUH WKH OLSRWR[LFLW\ DQG LPSDLUHG LQVXOLQ signaling caused by FFA in C2C12 myotube. This demonstrates potential implications to develop novel preventive or therapeutic strategies in T2D.

114

Abstract

PD08

GLP-1 RECEPTOR AGONIST AMELIORATES HIGH FAT DIET-INDUCED NEUROINFLAMMATION AND ANXIETY-LIKE BEHAVIOR IN MICE 1

HSIN-YING CHIOU, 2MING-HONG LIN, 1HE-JIUN JIANG, 1WEI-WEN HUNG, 3 SHIOU-LAN CHEN, 1PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University; Department of Microbiology and Immunology, Kaohsiung Medical University; 3Graduate Institute of Medicine, Collage of Medicine, Kaohsiung Medical University

2

Background: Obesity is associated with multiple comorbidities, such as metabolic abnormalities and cognitive dysfunction. Accumulating evidences indicate that neurodegenerative disorders are associated with chronic neuroinflammation. GLP-1is also produced by neuron and microglia to SURPRWH QHXURJHQHVLV DQG UHGXFH QHXURLQÀDPPDWLRQ */3 UHFHSWRU LV ZLGHO\ H[SUHVVHG RYHU EUDLQ including hypothalamus, cortex, hippocampus, cerebellum, and brain stem. Increasing evidences demonstrate a neuroprotective effect of GLP-1 RA, which is independent on the glucose-lowering effects. This study was designed to investigate the GLP-1 signaling in obesity-associated brain damage DQG HYDOXDWH WKH SRWHQWLDO EHQH¿W RI */3 UHFHSWRU DJRQLVW IRU FOLQLFDO DSSOLFDWLRQ Methods: In this study, mice were fed with high-fat-diet (HFD) for 16 weeks to induce obesity, and combined with or without weekly injection of GLP-1 RA (Bydureon dose500 ug/kg/w). Bodyweight, energy intake, and blood glucose were measured throughout 16 weeks. The behavior test ZDV SHUIRUPHG WKH GD\ EHIRUH VDFUL¿FH E\ RSHQ ¿HOG DVVD\ 7KH HIIHFWV RI */3 5$ RQ DVWURJOLRVLV PLFURJOLRVLV DQG LQÀDPPDWRU\ F\WRNLQH H[SUHVVLRQV RQ KLSSRFDPSXV K\SRWKDODPXV DQG FRUWH[ ZHUH examined by immunohistochemistry and western blot.

Results: Our results showed that GLP-1 RA ameliorated the HFD-induced obesity, locomotor activity, and anxiety-like behavior. Hippocampal astrogliosis was reduced by GLP-1 RA. +\SRWKDODPXV H[SUHVVLRQV RI SUR LQÀDPPDWRU\ F\WRNLQHV ,/ E 71)D DQG LQVXOLQ UHVLVWDQW UHODWHG SOCS3 expressions were reduced by GLP-1 RA. Moreover, GLP-1 RA reversed the HFD-related S(5. UHGXFWLRQ LQ FRUWH[ 7KHVH UHVXOWV LQGLFDWHG WKDW */3 5$ FRXOG LQKLELW WKH LQÀDPPDWLRQ LQ hippocampus and hypothalamus, and also improve the insulin sensitivity.

Conclusions: From our biochemical and histological evidences, GLP-1 RA could reduce QHXURLQÀDPPDWLRQ DQG LQVXOLQ UHVLVWDQFH ZKLFK PD\ FRQWULEXWH WR DPHOLRUDWLRQ RI WKH +)' LQGXFHG anxiety-like behavior.

115

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD09

ASSOCIATION BETWEEN URIC ACID LEVEL AND INCIDENCE OF MACROALBUMINURIA IN PEOPLE WITH TYPE 2 DIABETES MELLITUS: A 4.5-YEAR COHORT STUDY 1

YUN-JU LAI, 2YUN-JU LAI CHEN, 3LI-JUNG CHEN, 4PO-WEN KU, 5YUNG-FENG YEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan; 2Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan; 4Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan; 5Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan

Background: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairement. Nevertheless, the association between uric acid levels and the development of macroalbuminuria has been under-investigated in people with type 2 diabetes mellitus.

Methods: Patients with type 2 diabetes and regular outpatient visits were recruited from the Puli Branch of the Taichung Veterans General Hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the macroalbuminuria incidence. Univariate and multivariate Cox regression analysis were employed to explore the relation between uric acid and incident macroalbuminuria. Uric acid cutoffs for incident macroalbuminuria were determined with the receiver operator characteristic curve.

Results: :H LQFOXGHG TXDOL¿HG VXEMHFWV PHDQ DJH \HDUV ROG >VWDQGDUG GHYLDWLRQ 11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident macroalbuminuria were recognized. Serum uric acid was significantly associated with an increased ULVN RI LQFLGHQW PDFURDOEXPLQXULD DGMXVWHG KD]DUG UDWLR FRQ¿GHQFH LQWHUYDO S < 0.001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under WKH FXUYH VHQVLWLYLW\ VSHFL¿FLW\ IRU LQFLGHQW PDFURDOEXPLQXULD Conclusions: Serum uric acid was associated with incident macroalbuminuria among people with type 2 diabetes.

116

Abstract

PD10

TYROSINE-KINASE-INHIBITOR-INDUCED AUTOIMMUNE DIABETES MELLITUS 1

YEN-LIN HUANG, 1YUAN-HAW WU, 1JIA-YIN GUO, 1KUO-CHIN HUANG, 1 WEI-LUN HUANG, 1YIN-HUEI CHEN, 1MAO-TSU FUH, 1CHING-CHU CHEN 1

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

Introduction: According to published literature, iatrogenic hyperglycemia has been witnessed in patients undergoing TKI target therapy. The mechanism behind TKI-induced hyperglycemia is related to metabolites of the drugs that have activity against IGF-1R[1]. In fact, it was recorded that up to 41% of patients taking Pazopanib, a TKI, could experience hyperglycemia[2]. In this report, we present an autoimmune diabetes mellitus case that was possibly induced during the course of cancer treatment that included Pazopanib.

Case report: We present a 60-year-old female with BMI of 20.2 kg/cm2 and no medical history for metabolic diseases. Her family history was only significant for gout. Initially, this patient was diagnosed with right axillary high-grade myxofibrosarcoma with lung metastasis. She underwent surgical excision for the lesions and received adjuvant MAID regimen chemotherapy. Six months later, patient was diagnosed with recurrence of STS and a new primary lung adenocarcinoma. Patient underwent another lung wedge resection operation and initiated Pazopanib treatment, postoperatively.

Patient’s urine glucose concentration was 70 mg/dL before initiating Pazopanib therapy. Four months later, we incidentally found that patient’s HbA1c value was 9%. Due to difficulty in effectively controlling her blood glucose, C-peptide level and GADA titer were measured and laboratory data of < 0.1 ng/mL and 22.9 U/mL (Normal < 5.0) were obtained, respectively. She was completely dependent on insulin injection for blood glucose control soon after we discovered her hyperglycemia condition.

Discussion and Conclusion: The etiology of hyperglycemia and elevated HbA1c is unknown in this patient. The rapid progression to insulin dependence in less than 6 months makes the diagnosis of LADA for this patient less likely. We, however, strongly suspect the diagnosis of iatrogenic autoimmune diabetes mellitus in this case and it could be related to one or a combination of components during her cancer treatment course.

117

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD11

USING WHOLE EXOME NEXT GENERATION SEQUENCING TO IDENTIFY THE CAUSATIVE GENES IN TWO TAIWANESE FAMILIES OF MATURITY ONSET DIABETES OF THE YOUNG 1

YU CHEN, 2CHIH-SHAN CHEN, 2,3,4,5PEI-LUNG CHEN, 3,4,5WEI-SHIUNG YANG

1

Genetic Counseling Master Program, Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University (NTU); 2Department of Medical Genetics, NTU Hospital; 3Department of Internal Medicine, NTU Hospital; 4Graduate Institute of Medical Genomics and Proteomics, College of Medicine, NTU; 5Graduate Institute of Clinical Medicine, College of Medicine, NTU

Background: The monogenic form of diabetes mellitus (DM) has not been well investigated in Taiwan.

Method: We have recruited two Taiwanese families of maturity onset diabetes of the young (MODY). The genomic DNA of two affected members and one unaffected members from each family was collected for whole exome next generation sequencing (WE NGS). Bio-informatic processing taking linkage analysis, variant allele frequency (T;p.V42A) as the causative mutation in family A. In family B, the causative mutation is in glucokinase gene, GCK (c.1318G > T;p.E440X).

Conclusion: This study demonstrate that WE NGS is a sensible approach to identify the diabetes causative genes in Taiwanese MODY families.

118

Abstract

PD12

EVALUATE THE GLYCEMIC EFFECTS OF OCTREOTIDE AND SURGICAL RESECTION WITH INTRA-OPERATIVE RAPID INSULIN ASSAY IN INSULINOMA: A CASE REPORT 1

RU-LAI HUANG, 1KAI-PI CHENG, 1CHIH-CHEN WANG, 1HORNG-YIH OU, 2 SHIH-MING HUANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital; 2 Department of General Surgery, National Cheng Kung University Hospital

Background: Insulinoma is a rare neuroendocrine tumor that causes insulin over-secretion and IUHTXHQW K\SRJO\FHPLF HSLVRGHV $OWKRXJK VXUJLFDO UHVHFWLRQ LV WKH GH¿QLWH WUHDWPHQW RI LQVXOLQRPD octreotide, a somatostatin analog, is an alternative choice in certain circumstances. We reported a case of insulinoma whose glycemic variability were evaluated by continuous glucose monitoring (CGM).

Methods: A 79-year-old female without the past history of diabetes was found hypoglycemia (serum glucose: 45 mg/dL) with unconsciousness in February 2018. Hyperinsulinemic hypoglycemia (serum glucose 40 mg/dL, Insulin:12.08 uU/ml , C peptide:2.5 ng/ml) was confirmed. Abdominal magnetic resonance imaging and subsequent intra-arterial calcium stimulation study were therefore arranged, which revealed a 1.2 cm insulinoma at pancreatic head. Octreotide (0.05 mg per day via subcutaneous injection) was prescribed before the surgery and there was no more hypoglycemic episode detected by CGM. Results: The glycemic level rose from 128 mg/dl to 440 mg/dl in 10 hours after the octreotide injection, and the glycemic effect persisted for around 24 hours. For definite treatment, the patient underwent tumor enucleation with rapid insulin assays used. The serum insulin level changed from 41.61 uU/ml at baseline to 7.1 uU/ml and 5.7 uU/ml at 8 and 16 minutes after the tumor excision, respectively. Meanwhile, CGM demonstrated the glycemic levels at a range of 140 mg/dl to 200 mg/dl during the period of operation.

Conclusions: CGM can investigate the glycemic variability closely and timely. With the aid of this novel tool, the clinicians can comprehensively evaluate the glycemic effects of octreotide and tumor excision in the cases of Insulinoma.

119

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD13

GREATER LOW-DENSITY LIPOPROTEIN CHOLESTEROL VARIABILITY INCREASES THE RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1,3

WEI-HAO HSU, 1,2CHIA-WEI LAI, 1,4KUN-DER LIN, 1,5PI-JUNG HSIAO, 1,3,5,6 SHYI-JANG SHIN, 1,3,5MEI-YUEH LEE 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan; 2Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Taiwan; 3Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; 4Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Taiwan; 5Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; 6Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Taiwan

Background: Lipid variability has been shown to be associated with worse cardiovascular outcomes in patients with coronary artery disease. The main purpose of this study was to determine whether low-density lipoprotein cholesterol (LDL-C) variability can be used to predict cardiovascular events in patients with type 2 diabetes mellitus (DM).

Methods: A total of 5,354 patients with type 2 DM were enrolled in this study. Cardiovascular events including coronary artery disease, stroke, peripheral arterial disease, and cardiovascular death ZHUH GH¿QHG DV WKH VWXG\ HQGSRLQWV DQG VWDQGDUG GHYLDWLRQV RI OLSLG OHYHOV ZHUH XVHG WR GH¿QH LQWUD individual lipid variability.

Results: Univariate Cox proportional hazards analysis showed that LDL-C standard deviation KD]DUG UDWLR >+5@ FRQ¿GHQFH LQWHUYDO >&,@ WR S ZDV DVVRFLDWHG with an increased risk of cardiovascular events in patients with type 2 DM. Multivariate Cox proportional hazards analysis showed that an increase in LDL-C standard deviation significantly increased the risk of cardiovascular events (HR, 1.063; 95% CI = 1.025 to 1.102; p = 0.01). KaplanMeier analysis of cardiovascular event-free survival (log-rank p < 0.001) in the patients grouped according to tertile of the standard deviation of LDL-C showed that the patients in tertile 2 and tertile 3 had a worse cardiovascular event-free survival than those in tertile 1.

Conclusion: Variability in LDL-C is a predictor of cardiovascular events in patients with type 2 DM.

120

Abstract

PD14

THE ASSOCIATION BETWEEN GLYCATED ALBUMIN AND GLYCOHEMOGLOBIN IN DIABETIC RETINOPATHY OF PRE-DIABETES CHIA-WEI LAI, WEI-HAO HSU, KUN-DER LIN, PI-JUNG HSIAO, SHYI-JANG SHIN, MEI-YUEH LEE Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C

Background: Pre-diabetes is the stage before the onset of diabetes, which is often referred to as the gray area. Glycohemoglobin (HbA1c) is clinically used as the gold standard for glycemic control of diabetes, but it may be affected by the life of red blood cells and the condition of hemoglobin. *O\FDWHG DOEXPLQ *$ UHÀHFWV WKH DYHUDJH JOXFRVH LQGH[ IURP WKH SUHYLRXV WR ZHHNV ,W FKDQJHV LQ D VKRUWHU SHULRG RI WLPH WKDQ +E$ F DQG LV VXSHULRU WR +E$ F LQ UHÀHFWLQJ ÀXFWXDWLRQV LQ EORRG glucose. Correlation between GA concentration and severity of diabetic retinopathy has been reported in patients with type 2 diabetes. However, there are limited studies to investigate the association between GA and diabetic retinopathy in pre-diabetic patients in Taiwan.

Methods: This study recruited 291 patients with pre-diabetes from January 2016 to February 2017. Blood and urine samples were obtained from all patients after fasting for 12 hours within 1 month of enrollment, including fasting glucose, lipid profile, HbA1c, GA, urine microalbumin and urine creatinine.

Results: A total of two hundred and ninety-one pre-DM patients are included. In the univariate analysis, diabetic retinopathy is found to be associated with older age, male, high systolic blood pressure, low body mass index, high GA, high HbA1C, low total cholesterol and low eGFR. After multivariate logistic regression analysis, old age, male, high systolic blood pressure, high HbA1C, and ORZ WRWDO FKROHVWHURO DUH VLJQL¿FDQWO\ DVVRFLDWHG ZLWK GLDEHWLF UHWLQRSDWK\ LQ SDWLHQWV ZLWK SUH '0 EXW GA is not.

Conclusions: ,Q WKH SUHGLDEHWLF SRSXODWLRQV KLJK +E$ & LV VLJQL¿FDQWO\ DVVRFLDWHG ZLWK GLDEHWLF retinopathy. However, GA is not associated with diabetic retinopathy in this population.

121

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD15

ENDOTHELIN-1 STIMULATES PREADIPOCYTE CELL GROWTH THROUGH MULTIPLE KINASE SIGNALING PATHWAYS 1

AN-CI SIAO, 1TSAI-YUN CHAN, 2HUI-CHEN KU, 3YI-WEI TSUEI, 3YEN-YUE LIN, 4 YOW-CHII KUO, 1YUNG-HSI KAO 1

Department of Life Sciences, National Central University, Jhongli City, Taoyuan, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3Department of Emergency, Taoyuan Arms & Forces General Hospital, Taoyuan, Taiwan; 4Department of Gastroenterology, Landseed General Hospital, Taoyuan, Taiwan

Background: Endothelin (ET)-1 possesses numerous functions in regulating fat cell activity. This study investigated the pathways involved in ET-1 modulation of 3T3-L1 preadipocyte proliferation.

Methods: 3T3-L1 preadipocytes were treated with ET-1 in the presence or absence of its signal molecule inhibitor, and then cell number, cell proliferation, and growth-controlling proteins were measured by trypan blue method, bromodeoxyuridine (BrdU) incorporation, and Western blot, respectively.

Results: Preadipocyte proliferation as indicated by an increased number of cells and greater incorporation of BrdU was stimulated by ET-1 in dose- and time-dependent manners. ET-1 also timeor dose-dependently stimulated phosphorylations of signal transducer and activator of transcription 67$7 F -XQ $03 DFWLYDWHG SURWHLQ NLQDVH $03.

SURWHLQ NLQDVH & DOSKD 3.&Į ȕ,, DQG mitogen-activated protein kinase (MAPK) pathway proteins, ERK, but not JNK and p38. Treatment ZLWK DQ LQKLELWRU RI WKH (7 W\SH $ UHFHSWRU VXFK DV %4 EXW QRW ZLWK WKH (7 W\SH % UHFHSWRU DQWDJRQLVW %4 EORFNHG (7 LQFUHDVHG WKH OHYHOV RI FHOO SUROLIHUDWLRQ DQG SKRVSKRU\ODWHG OHYHOV RI (5. DQG F -XQ 0RUHRYHU SUHWUHDWPHQW ZLWK VSHFL¿F LQKLELWRUV RI HLWKHU -DQXV NLQDVH -$.

STAT-3, ERK1/2, JNK, AMPK, and PKC prevented ET-1-increased levels of cell proliferation and UHGXFHG WKH (7 VWLPXODWHG SKRVSKRU\ODWLRQ RI 67$7 (5. F -XQ $03. DQG 3.&Į ȕ,, UHVSHFWLYHO\ 7KH VSHFL¿F LQKLELWRUV RI VSKLQJRVLQH NLQDVH 6SK. VXFK DV 6., ,, DQG 3) EXW QRW ceramide synthase (CerS) such as Fumonisin B2, were also found to suppress ET-1-induced increases in cell number, BrdU incorporation, and ERK and c-Jun phosphorylations. However, the p38 MAPK antagonist SB203580 did not alter the effect of ET-1.

Conclusions: These results imply that functional proteins of ETAR, JAK2, ERK1/2, c-Jun, $03. 3.&Į 6SK. EXW QRW (7%5 S 0$3. RU &HU6 DUH QHFHVVDU\ IRU WKH (7 VWLPXODWLRQ of preadipocyte proliferation. The ETAR-dependent and ETBR-independent effects of ET-1 were VXSSRUWHG E\ PXULQH SULPDU\ FHOO VWXG\ VKRZLQJ WKDW %4 EXW QRW %4 VXSSUHVVHG (7 LQGXFHG increases in both cell number and cell proliferation of stromal-vascular preadipocyte fraction.

122

Abstract

PD16

THE ROLE OF HYPOGLYCEMIC AGENTS USE IN CARDIOVASCULAR EVENTS IN INTENSIVELY CONTROLLED DIABETES 1

WEI-LUN WEN, 1NAI-WEI SHEU, 1SHU-HENG HUANG, 2KUN-DER LIN, 1 PI-JUNG HSIAO, 1SHYI-JANG SHIN, 1MEI-YUEH LEE 1

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

Background: Physicians aim to manage diabetic patients with balancing adequate glycemic control and occurrence of hypoglycemia to improve patients’ health. It remains unclear whether cardiovascular outcomes were associated with the use of hypoglycemic agents (insulin dependent DJHQWV YV LQVXOLQ LQGHSHQGHQW DJHQWV LQ SDWLHQWV ZLWK LQWHQVLYHO\ FRQWUROOHG GLDEHWHV +E$ &

Methods: We enrolled 3,261 type 2 diabetes patients with two consecutive HbA1C levels of 6.4% or lower from Kaohsiung Medical University Research Database during 2010 to 2011. All patients were followed until December 31, 2015. The study cohort was divided into two groups: patients receiving insulin dependent agents (sulfonylureas and insulin) and those receiving insulin independent agents (metformin, acarbose, pioglitazone and dipeptidyl peptidase 4 inhibitors) for glycemic control.

Results: During the mean follow-up period of 4.2 ± 0.9 years, 325 patients had cardiovascular events. Compared to the insulin independent group, the insulin dependent group had significantly higher hypoglycemic episodes and cardiovascular events (both p < 0.001). In multivariate analysis, the patients in the insulin dependent group were associated with an increased risk of cardiovascular events KD]DUG UDWLR FRQ¿GHQFH LQWHUYDO í S

Conclusions: Type 2 diabetes patients receiving insulin dependent agents were associated with an increased risk of cardiovascular events compared to those receiving insulin independent agents, suggesting that insulin independent agents may be preferential in diabetic patients with high risk of hypoglycemia.

123

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD17

HYPERGLYCEMIA AND HYPOGLYCEMIA TRENDS WITH CURRENT GLUCOSE-LOWERING AGENTS IN TAIWAN ON YEAR 2005-2013 1

SHU-HENG HUANG, 1WEI-LUN WEN, 1NAI-WEI SHEU, 2KUN-DER LIN, 1PI-JUNG HSIAO, 1SHYI-JANG SHIN, 1MEI-YUEH LEE 1

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

Background: To examine temporal trends in utilization of glucose-lowering medications, glycemic control, and rate of severe hypoglycemia and hyperglycemia among patients with type 2 diabetes (T2DM).

Methods: Using claims data from 1 million insured Taiwan National Health Insurance patients with T2DM from 2005 to 2013, we estimated the annual 1) age- and sex-standardized proportion of patients who filled each class of agents and sex-standardized rate of severe hypoglycemia and hyperglycemia among those using medications.

Results: From 2005 to 2013, use increased for metformin and sulfonylureas was still observed despite increased use of dipeptidyl peptidase 4 inhibitors since entry on year 2009 to 2013. However, use in insulin, thiazolidinediones , glucagon like peptide -1 receptor agonist meglitinides, and alpha glucosidase inhibitors was stable. The overall rate of severe hypoglycemia and hyperglycemia remained the same until year 2011, declined modestly .

Conclusions: During the recent 9-year period, the use of glucose-lowering drugs has changed DPRQJ SDWLHQWV ZLWK 7 '0 VLQFH WKH HQWU\ RI '33 LQKLELWRUV VLQFH EXW WKLV HIIHFW RQO\ UHÀHFW after 2 years of entry of DPP4 inhibitors on year 2011, which overall rate of severe hypoglycemia and hyperglycemia remains largely unchanged before 2011 and declined after.

124

Abstract

PD18

6*/7 ,1+,%,725 3527(&76 Ǻ &(//6 :+,/( 68/)21</85($ DIDN’T IN DB/DB MICE VIA RETINOL SIGNALING 1

CHAO-HUNG CHEN, 1PI-CHEN LIN, 1KUN-DER LIN, 1MEI-YUEH LEE, 1 PI-JUNG HSIAO, 1YI-CHI HUANG, 1 烗 SING -YI HUANG, 1SHYI-JANG SHIN 1

Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors have been proved to be beneficial for CV and renal outcome in diabetic patients. However, the protective mechanism of 6*/7 LQKLELWRU LV VWLOO UHVHDUFKHG 5HFHQWO\ YLWDPLQ $ GH¿FLHQF\ LV GHPRQVWUDWHG WR FDXVH ORVV RI mass on pancreas. Our study also indices that aberrant intracellular retinol signaling is associated with diabetic kidney. The vitamin A metabolism is also regulated by RBP4/STRA6/CRBP1/LRAT/RARs pathway in pancreatic tissue.

Methods: Thus, this study aims to investigate the protective effects of SGLT2 inhibitor, HPSDJOLÀR]LQ RQ SDQFUHDWLF 5%3 675$ &5%3 /5$7 5$5V SDWKZD\ 'LDEHWLF GE GE PLFH ZHUH WUHDWHG ZLWK HPSDJOLÀR]LQ RU JOLEHQFODPLGH IRU ZHHNV LQ WKH HDUO\ VWDJH RI GLDEHWHV ZHHNV RI DJH

7KLV VWXG\ DQDO\]HG 5%3 675$ &5%3 /5$7 5$5V SDWKZD\ IXQFWLRQDO PDUNHUV RI SDQFUHDWLFȕ cells including MafA, Pdx1, and NKX6.1 in pancreas of db/db, glibenclamide-treated db/db, and HPSDJOLÀR]LQ WUHDWHG GE GE PLFH Results: In pancreas of db/db mice, insulin secretion, MafA, Pdx1, and NKX6.1 expression were VLJQL¿FDQWO\ LQFUHDVHG E\ HPSDJOLÀR]LQ )XUWKHUPRUH WKH GLVUXSWLRQ RI 5%3 675$ &5%3 /5$7 5$5V SDWKZD\ ZDV UHFRYHUHG E\ HPSDJOLÀR]LQ 7KH FRQFHQWUDWLRQ RI UHWLQRO DQG UHWLQRLF DFLG ZHUH also conserved in pancreas of empagliflozin-treated db/db mice. However, glibenclamide could not SURGXFH WKLV EHQH¿FLDO HIIHFW DV FRPSDUHG ZLWK HPSDJOLÀR]LQ Conclusions: 7KHUHIRUH WKLV VWXG\ GHPRQVWUDWHV WKDW HPSDJOLÀR]LQ H[HUWV SURWHFWLYH HIIHFWV LQ 5%3 675$ &5%3 /5$7 5$5V SDWKZD\ DQG OHDGV WR SURWHFW ȕ FHOO G\VIXQFWLRQ RI GE GE PLFH

125

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD19

ASSOCIATION OF HBA1C VARIABILITY AND RENAL PROGRESSION IN PATIENTS WITH TYPE 2 DIABETES WITH CHRONIC KIDNEY DISEASE STAGES 3–4 1

NAI-WEI SHEU, 1WEI-LUN WEN, 1SHU-HENG HUANG, 2KUN-DER LIN, 1 PI-JUNG HSIAO, 1SHYI-JANG SHIN, 1MEI-YUEH LEE 1

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

Background: Little is known about the predictive value of glycosylated hemoglobin (HbA1c) variability in patients with advanced chronic kidney disease (CKD). The aim of this study was to investigate whether HbA1c variability is associated with progression to end-stage renal disease in diabetic patients with stages 3–5 CKD, and whether different stages of CKD affect these associations.

Methods: Three hundred and eighty-eight patients with diabetes and stages 3–5 CKD were enrolled in this longitudinal study. Intra-individual HbA1C variability was defined as the standard GHYLDWLRQ 6' RI +E$ F DQG WKH UHQDO HQGSRLQW ZDV GH¿QHG DV FRPPHQFLQJ GLDO\VLV Results: The results indicated that, during a median follow-up period of 3.5 years, 108 patients started dialysis. Adjusted Cox analysis showed an association between the highest tertile of HbA1c 6' WHUWLOH YV WHUWLOH DQG D ORZHU ULVN RI WKH UHQDO HQGSRLQW KD]DUG UDWLR FRQ¿GHQFH LQWHUYDO ± S LQ WKH SDWLHQWV ZLWK DQ +E$ F OHYHO DQG VWDJHV ± &.' EXW not in stage 5 CKD. Further subgroup analysis showed that the highest two tertiles of HbA1c SD were associated with a lower risk of the renal endpoint in the group with a decreasing trend of HbA1c.

Conclusions: Our results demonstrated that greater HbA1c variability and a decreasing trend of HbA1c, which may be related to intensive diabetes control, was associated with a lower risk of SURJUHVVLRQ WR GLDO\VLV LQ WKH SDWLHQWV ZLWK VWDJHV ± &.' DQG SRRU JO\FHPLF FRQWURO +E$ F

126

Abstract

PD20

COMPARE THE EFFICACY OF TOUJEO WITH LEVEMIR AS BASAL INSULIN THERAPY IN NON-CRITICAL HOSPITALIZED DM POOR CONTROL PATIENTS IN A REGIONAL TEACHING HOSPITAL JUI-HSIANG LI, SU-HUEY LO Department of Internal Medicine Tao-Yuan General Hospital

Background: 7R FRPSDUH WKH HI¿FLHQF\ RI 7RXMHR ZLWK /HYHPLU DV EDVDO LQVXOLQ WKHUDS\ LQ QRQ critical DM poor control patients Methods: This study is a retrospectively chart review study. Non-ciritical hospitalized poor control type 2 diabetes who were consulted endocrinologist with increasing insulin doses or random access to initiating Toujeo hs + Novorapid tidac or Levemir hs + novorapid tid ac from 1, July, 2018 to 1RY ZHUH HQUROOHG :H DVVHVVHG WKH HI¿FDF\ RI EORRG JOXFRVH FRQWURO DQG K\SRJO\FHPLD ULVN Results: Twenty patients received Toujeo + Novorapid control and another twenty patients received Levemir+ Novorapid control. There were no significant difference in baseline character such as age, body weight, height, A1C and Cr level. The pre-treatment glucose level is similar in both group. In Toujeo group, the four points blood glucose level ( tid ac+ hs, mg/dl ) is 251 ± 58.1, 265.8 ± 73.6, 301.4 ± 100.3, 272.2 ± 85.6. In Levemir group, the blood glucose level is 230.0 ± 85.1, 293.2 ± 85.0, 274.3 ± 99.2, 296.3 ± 74.1. After seven days intervention, the four points blood glucose level in Toujeo group is 206.4 ± 84.0, 226.2 ± 83.0, 209.3 ± 88.7, 207.2 ± 76.0, while in Levemir group the blood sugar is 187.1 ± 92.9, 219.7 ± 109.8, 209.9 ± 95.8, 7KHUH ZDV VWLOO QR VLJQL¿FDQW GLIIHUHQFH LQ ERWK JURXS ,Q WKH ¿UVW GD\ WKH LQVXOLQ GRVH LV 7RXMHR ,8 TKV 1RYRUDSLG IU tidac and Levemir 17 ± 7IU qhs+ Novorapid 11 ± 3IU tidac. In the seventh day, the insulin dose is Toujeo 19 ± 9IU qhs + Novorapid 14 ± 5IU tidac and Levemir 17 ± 5U qhs + Novorapid 13 ± 3IU tidac. Similar hypoglycemia risk was noted in both group (6 times in Toujeo group and 7 times in Levemir group).

Conclusions: In this study, similar glycemic control and hypoglycemia risk was noted with Toujeo and Levemir control. But the rate of glycemic control reaching the target was low. The goal of fasting (70~140mg/dl), pre-lunch, pre-dinner and pre-bedtime (70~180mg/dl) blood glucose was 26.3%, 25%, 47%, 15% in Toujeo group and 37.5%, 54.5%, 46.7%, 20% in Levemir group respectively. We should aggressive titrate the insulin dose to reach the goal to improve the care quality and outcome.

127

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD21

TO EVALUATE THE EFFICACY AND SAFETY OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST PLUS BASAL INSULIN THERAPY IN SUBJECTS WITH TYPE 2 DIABETES WITH POOR GLYCEMIC CONTROL UNDER TWICE-DAILY PREMIXED INSULIN THERAPY 1

JHIH-SYUAN LIU, 1SHENG-CHIANG SU, 1CHIEH-HUA LU, 1CHIEN-HSING LEE, 1 CHANG-HSUN HSIEH 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Background: The current guideline recommends several strategies to intensify injectable therapy LQ GLDEHWHV 7KLV VWXG\ H[SORUHG WKH SRVVLEOH WKHUDSHXWLF EHQH¿WV RI FRPELQDWLRQ ZLWK JOXFDJRQ OLNH peptide-1 receptor agonist (GLP-1 RA) and basal insulin among subjects of type 2 diabetes (T2DM) previously treated with premixed insulin.

Methods: It is a single arm, open study. Anti-diabetic regimen was shifted to GLP-1 RA plus basal insulin to replace previous treatment of premixed insulin with inadequate glycemic control (HbA1C level between 7 to 11%) T2DM subjects. The glycemic index, clinical cardiovascular risk SUR¿OHV DQG VDIHW\ LVVXHV ERG\ ZHLJKW DQG K\SRJO\FHPLD EHIRUH DQG DIWHU WKUHH PRQWKV WUHDWPHQW PRGL¿FDWLRQ ZDV HYDOXDWHG Results: A total twenty subject with 55% males; mean age of 58 ± 11 years, mean diabetes GXUDWLRQ RI \HDUV DQG EDVHOLQH +E$ F OHYHO RI ZHUH LQFOXGHG $IWHU PRGL¿FDWLRQ RI WUHDWPHQW VWUDWHJ\ WKHUH ZHUH VWDWLVWLFDO VLJQL¿FDQFH LQ ERG\ ZHLJKW UHGXFWLRQ RI NJ S

BMI reduction of 1.1 kg/m2 (p < 0.001), HbA1c improvement of 0.9% (p < 0.001), fasting plasma glucose reduction of 50 mg/dL (p = 0.004), and LDL cholesterol reduction of 11 mg/dL (p = 0.012).

However, the incidence of hypoglycemia was not different between these two treatment strategies.

Conclusions: In this pilot study, the combination treatment with GLP-1 RA and basal insulin VKRZV D VLJQL¿FDQW LPSURYHPHQW RI JO\FHPLF LQGLFHV DQG FDUGLRYDVFXODU EHQH¿W DPRQJ SDWLHQWV ZLWK uncontrolled T2DM on previous therapy with premixed insulin. It provided important information for physicians to decide to modify therapeutic strategy as individualized needs. A larger scaled study is QHFHVVDU\ WR EH FRQGXFWHG WR YDOLGDWH WKHVH ¿QGLQJV

128

Abstract

PD22

LIRAGLUTIDE INHIBITS HEPATITIS C VIRUS REPLICATION THROUGH AN AMP ACTIVATED PROTEIN KINASE DEPENDENT MECHANISM 1

MEI-YUEH LEE, 2WEI-CHUN CHEN, 1WEI-HAO HSU, 1YU-LI LEE, 2JIN-CHING LEE, 1 SHYI-JANG SHIN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine,Kaohsiung Medical University Hospital Chung-Ho Memorial Hospital; 2Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan

Background: Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication.

Methods: A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were H[WUDFWHG WR GHWHUPLQH WKH HI¿FLHQF\ RI +&9 UHSOLFDWLRQ $YD FHOOV ZHUH WUHDWHG ZLWK OLUDJOXWLGH DQG cell viability was calculated. Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected.

Results: Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. /LUDJOXWLGH GHFUHDVHG WKH FHOO YLDELOLW\ RI +&9 51$ DW DQ RSWLPXP FRQFHQWUDWLRQ RI ȝJ ml, activated 5’ adenosine monophosphate-activated protein kinase (AMPK) and phosphorylatedtransducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA. Conclusions: Liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.

129

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD23

INTENTIONAL INSULIN OVERDOSE-A CASE REPORT I-MIN PAN, WEI-HSIN HSU Division of Endocrinology and Metabolism, Department of Internal Medicine, Tainan Sin-Lau Hospital, Taiwan, R.O.C.

A 55-year-old male was a case of type 2 DM, positive hepatitis C virus antibody. Insulin novomix 30/70 was used for diabetes control at a local hospital. He injected around 480-600unit insulin to right lower abdominal wall around 8-9 PM after quarrel with his family. He felt weakness and lied on the roadside. He was found by police and emergency medical technician(EMT). On ambulance, finger sugar showed 53 mg/dl, conscious level E2V2M4. D50W(50% dextrose) 40 cc was given intravenously. GCS improved to E4V1M5. At ER, blood sugar revealed 95 mg/dl. He was started on a dextrose 10% drip at 60-100mL/h. Upon physical examination, there are several injection trace with ecchymosis but no induration on right lower abdomen (12 hours post insulin injection). During the first 24 hours in the intensive care unit and ward, low blood sugar levels between 43-80mg/dl UHTXLULQJ ' : EROXVHV IRXU WLPHV WR NHHS ¿QJHU VXJDU ! PJ GO /DERUDWRU\ H[DPLQDWLRQ VKRZHG high lactic acid level, hypokalemia, hypophosphatemia, very high insulin level and low C-peptide.

Despite continuous drip 9% dextrose at 100mL/h and a liberal carbohydrate diet, the last episode of hypoglycemia 47 mg/dl was observed in the early morning 5AM on 2nd day when was 33th hours post massive insulin dose injection. After this hypoglycemia, blood sugar elevated. We started insulin injection subcutaneously for diabetes control. He was disposed to psychiatrist for further evaluation.

130

Abstract

PD24

HIGH LEPTIN TO SUBCUTANEOUS ABDOMINAL FAT RATIO CHANGE REDUCE METABOLIC SYNDROME RISK IN TAIWANESE OBESE MEN AFTER WEIGHT REDUCTION PROGRAM 1,2

CHUN-CHENG LIAO, 3,4,5I-TE LEE, 4,6SHIH-YI LIN, 7WEN-JANE LEE, 3,4,8 WAYNE HUEY-HERNG SHEU 1

Department of Family Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan; 2National Defense Medical Center, Taipei, Taiwan; 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5School of Medicine, Chung Shan Medical University, Taichung, Taiwan6 Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taiwan; 7Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 8Rong Hsing Research Center For Translational Medicine, National Chung Hsing University, Taichung, Taiwan

Background: Leptin is associated with metabolic syndrome (MetS) but not know that leptin to subcutaneous abdominal fat area ratio (leptin/SAFA ratio) or change after weight reduction program (WRP) whether is associated with MetS. This study was to evaluate leptin to subcutaneous abdominal fat ratio or change whether is associated with MetS in Taiwanese obese men.

Methods: Forty middle-aged, obese men (age: 42.8 ± 10.7 years and body mass index: 33.8 ± 4.0 kg/m2) were enrolled and thirty-six with or without MetS completed 12-week WRP which was conducted in the Division of Endocrinology and Metabolism at Taichung Veterans General Hospital LQ 7DLZDQ 0HW6 FULWHULD ZDV XVHG WKH PRGL¿HG $GXOW 7UHDWPHQW 3DQHO ,,, IRU 7DLZDQHVH SRSXODWLRQ Anthropometry and metabolic risk factors were measured before and after WRP. Subcutaneous abdominal fat area (SAFA), intra-abdominal fat area (IAFA) before and after WRP were determined by magnetic resonance imaging (MRI). Multiple logistic regression analysis estimate the odds of reducing MetS by adjusting age, baseline SAFA, IAFA and leptin/SAFA ratio change after WRP. Results: 2YHU ZHHN :53 PRGHUDWH ZHLJKW UHGXFWLRQ DERXW DQG VLJQL¿FDQW FKDQJH RI waist circumference, systolic and diastolic blood pressure, fasting sugar, HDL-ch and triglyceride after :53 ZHUH IRXQG 6LJQL¿FDQW GHFUHDVH LQ +20$ ,5 6$)$ DQG ,$)$ DIWHU :53 ZHUH DOVR IRXQG Total 34 participants have MetS before WRP and 15 participants progressed not to MetS, whereas 15 did. 50% of MetS risk reduction was detected by using McNemar’s Test analysis after this program intervention. Multiple logistic regression analysis also showed lower odds of MetS risk with 1-SD greater leptin/SAFA ratio change (OR, 0.59; 95% CI, 0.01-0.74; p = 0.029) after adjustment including age, baseline VAT, SAT and leptin/SAFA ratio change after WRP. Conclusions: The effect of WRP to reduce metabolic syndrome risk in Taiwanese obese men LV VLJQL¿FDQWO\ DVVRFLDWHG ZLWK OHSWLQ 6$)$ UDWLR FKDQJH )XUWKHU UHVHDUFK LV QHHGHG WR FRQ¿UP WKLV association in other ethnic/racial populations.

131

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD25

DIPEPTIDYL PEPTIDASE 4 INHIBITORS CAN DECREASE ALLERGIC RHINITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN TAIWAN 1.2.3

HSIN -HUNG CHEN

1.

Institute of Medicine and Public Health, Chung Shan Medical University, Taichung, Taiwan; 2.College of Nursing and Health Sciences, Dayeh University, Changhua, Taiwan; 3.Division of Metabolism & Endocrinology, Changhua Christian Hospital, Changhua, and Nantou Christian Hospital, Nantou, Taiwan

Background: Dipeptidyl peptidase 4 inhibitors (DPP4i) are considered to be a safer drug with rare side effects among anti-diabetic agents. Most frequent reported adverse reaction with DPP4i are nasopharyngitis (3.5-13.2%) and upper respiratory infection (4.5-11%). But we think some of the adverse reports may be the allergic rhinitis .This study was designed to evaluate the association between allergic rhinitis and DPP4i user in type 2 diabetic patients in Taiwan.

Methods: There were 28810 patients with T2DM from Taiwan National Health Insurance 'DWDEDVH :H LGHQWL¿HG LQGLYLGXDOV ZLWK 7 '0 ,&' &0 [ DQG WKH XVH RI '33 L GD\V RU greater as a DPP4i cohort and subjects never use DPP4i as a control cohort from 2009 to 2017. The &R[ SURSRUWLRQDO KD]DUG UHJUHVVLRQ PRGHO ZDV XVHG WR HVWLPDWH WKH KD]DUG UDWLRV +5V DQG FRQ¿GHQFH intervals (CIs) for the cohorts. Nonparametric Kaplan-Meier analysis was used to determine the cumulative event rates of allergic rhinitis, and the log-rank test was used to test the difference between these two cohorts. Data management and analysis were carried out using SAS 9.4 software (SAS ,QVWLWXWH &DU\ 1& 86$ 7KH VLJQL¿FDQFH OHYHO ZDV VHW DW D S YDOXH RI OHVV WKDQ IRU WZR VLGHG testing.

Results: We identified 6443 individuals taking DPP4i and 22367 matched cohort without taking DPP4i. DPP4i cohort had a higher proportion of comorbidities with CAD, stroke, HTN and dyslipidemia .The incidence rate of allergic rhinitis was higher in non-DPP4i cohort(1.56 vs1.23) in our study. The subgroup analysis of our study also showed that in non-DPP4i cohort, there was higher incidence rate of allergic rhinitis in female(1.75vs 1.16) ,age more than 40 years-old(1.52vs1.16),age more than 65 years-old (1.60vs 1.23) and diabetic patients with comorbidities group(1.58vs 1.22).

Conclusions: DPP-4 i were associated with an increased adverse reaction with nasopharyngitis and upper respiratory infection but not allergic rhinitis. The mechanism of immune change with DPP4 i may be one of the reason.

132

Abstract

PD26

FULMINANT TYPE 1 DIABETES MELLITUS: A REPORT OF A SINGLE-CENTER EXPERIENCE NAN-HAU HUANG, CHEWN-YI YANG, KAI-JEN TIEN, NAI-CHENG YEH, SHANG-GYU LEE, MEI-CHEN YEH Chi Mei Medical Center Endocrinology Department

)XOPLQDQW W\SH GLDEHWHV PHOOLWXV )7 '0 LV D QHZ VXEW\SH RI W\SH GLDEHWHV ¿UVWO\ SURSRVHG

by Imagawa in 2000. It is a clinical condition that is characterized by remarkably rapid and complete SDQFUHDWLF ȕ FHOO GHVWUXFWLRQ UDSLG RQVHW RI K\SHUJO\FHPLF V\PSWRPV IROORZHG E\ NHWRDFLGRVLV DQG ORZ JO\FDWHG KDHPRJORELQ OHYHO )7 '0 LV FRQ¿UPHG ZKHQ DOO WKH IROORZLQJ ¿QGLQJV DUH SUHVHQW (1) Occurrence of diabetic ketosis or ketoacidosis soon (approximately 7 days) after the onset of K\SHUJO\FDHPLF V\PSWRPV HOHYDWLRQ RI XULQDU\ DQG RU VHUXP NHWRQH ERGLHV DW ¿UVW YLVLW

3ODVPD JOXFRVH OHYHO PPRO / PJ G/ DQG JO\FDWHG KDHPRJORELQ OHYHO 1*63 YDOXH D DW ¿UVW YLVLW 8ULQDU\ &ƮSHSWLGH H[FUHWLRQ ȝJ GD\ RU IDVWLQJ VHUXP &Ʈpeptide level < 0.3 ng/mL (< 0.10 nmol/L) and <0.5 ng/mL (< 0.17 nmol/L) after intravenous glucagon (or after meal) load at onset.

However, the pathophysiology of this condition remains still unclear. Most of FT1DM have been reported in Asian populations and rare cases have been reported in Caucasians or native American. The prevalence of FT1DM is estimated to account for 1.5% to 19.4% in Asia. Here, we present the cases diagnosed with FT1DM in a medical center in Tainan, Taiwan.

133

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE01

A WOMAN WITH STIFF-PERSON SYNDROME—AUTOIMMUNE POLYENDOCRINE SYNDROME TYPE 2 1

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

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chimei medical center, Taiwan, R.O.C.

A 41-year-old woman was seen in the emergency department(ED) at this hospital because of trunkal spasm and rigidity.

The patient had been well until approximately 1 week before this ED visit, when spasms and rigidity developed in her trunk and neck. The muscle spasms and rigidity progressively worsened. One GD\ EHIRUH WKH (' YLVLW WKH VSDVPV OHG WR GLI¿FXOW\ LQ VLWWLQJ XS IURP EHG DQG VKH KDG GLI¿FXOW\ LQ walking. She came to the emergency department at this hospital.

At ED, her serum glucose was 476mg/dL, and hyperglycemic chorea was the impression. Her serum ketone body was 0.8mmol/L and blood osmolality was 310 mOsm/kg. She was given 6 unit of insulin subcutaneously, normal saline hydration and diazepam intravenously, and then she was discharged from ED with the prescription of oral-form antidiabetic medicine, Metformin(500mg) twice daily after meal. And she was refer to endocrine outpatient clinic 2 days later.

At endocrine outpatient clinic, her blood glucose was 230mg/dL, however, the spasms and rigidity in trunk and neck still existed. Hyperglycemic chorea is not likely. This patient mentioned that she was told to have suspected hyperglycemia during her pregnancy more than 10 years ago, and she was also told that her blood sugar returned to normal range after her pregnancy. She denied any other systemic disease except for the suspected hyperglycemia.

She denied allergic to any medicine. She did not smoke, drink alcohol, or use illicit drugs. She denied family history of any systemic disease.

On examination, the vital signs were normal, except for elevated heart rate. The abdomen was rigid due to muscle spasm without tenderness on palpation. Mild stared eyes were seen. The remainder of the examination was normal. The hematocrit, hemoglobin level, platelet count, creatinine, and GPT were normal. Other test were as follows: Hba1c 10.6 %, GAD-65 > 2000 U/mL. Thyroid hormones were check because mild stared eyes were noted. (T4: 9.2ug/dl, TSH 0.03uIU/ml, free T4 1.77ng/dL, anti-TPO 190.9IU/mL).

Thyroid sonography showed mild enlargement of bilateral lobes of thyroid gland with mild increased vascularity. I131 uptake scan was performed and the thyroid uptake at 24 hour was 80%(Normal range 15%-25%), consistent with diffuse thyrotoxicosis.

Glucagon test for suspected type 1 diabetes was performed and the result revealed C-peptide at 134

Abstract

0 minute 0.65 ng/mL, at 6th minute 1.07 ng/mL, which is compatible with type 1 diabetes mellitus.

Neurologist was consulted and stiff-person syndrome is highly suspected.

The current impression is: Autoimmune polyendocrine syndrome type 2 ͒(Type 1 diabetes mellitus and Graves’ disease) Stiff-person syndrome͒​͒The current treatment is basal bolus insulin for diabetes mellitus and oral form diazepam for muscle spasm and stiffness.

135

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE02

A CASE REPORT : ANTITHYROID DRUG-INDUCED AGRANULOCYTOSIS IN A 55 YEAR-OLD WOMAN 1

YAN-YU LIN, 1,2CHUNG-HUEI HSU, 1CHEN LING HUANG, 1SHUEN-FU WENG, 1 YU-PEI LIN 1

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

Introduction: Antithyroid drugs are used commonly in hyperthyroidism patients, which includes propylthiouracil , carbimazole and its active metabolite methimazole. Most patients have several EHQH¿WV DQG MXVW D IHZ ULVNV DIWHU XVLQJ $7'V +RZHYHU VRPH FRXOG SUHVHQW DV VHYHUH FRPSOLFDWLRQ ATD-induced agranulocytosis is rare, but the severity of this possibly condition could be lifethreatening. Earlier diagnosis and the appropriated managements are very important.

Case Report: This 55-year-old woman has history of hyperthyrodism under Methimazole(5 mg) 1 tab TID treatment. After three months later, fever with sore throat was noted that she came to ER for help. In addition, right-lower quadrant abdominal dull pain was also occurred. Initial lab data revealed that: WBC 860/ul, Seg 2.0% (ANC 17.2), CRP 14.13mg/dl. Influenza A, B were all negative. Abdomen CT revealed prominent appendix with relative mild thickening wall (Fig. 1). Due to neutropenia, oncologist was also consulted and peripheral blood smear was performed. No blast cell nor promyelocyte were seen. Under the impression of Antithyroid drug-Induced agranulocytosis , we stopped methimazole use and the patient was admitted for observation with empiric antibiotics DV 3LSHUDFLOOLQ 7D]REDFWDP PJ 4 + ZDV DOVR JLYHQ $IWHU IROORZLQJ KHU ODE GDWD GD\V ODWHU stabilized WBC/DC was noted, and all parameters were within normal range after 1 week follow up.

No fever noted and right-lower quadrant abdominal dull pain was also subsided then. The patient was arranged radioactive iodine then for restore an euthyroid state.

Discussion: Agranulocytosis occurs in only 0.2–0.5% of patients with Graves’ disease receiving antithyroid drugs. The rarity of this side effect often makes our clinical physicians miss it and probably let patients life-threatening. High fever and sore throat are the most common presenting signs, but patients may also be asymptomatic. Genome-wide association studies in ethnic Chinese people in Taiwan and Hong Kong have shown an association between agranulocytosis induced by antithyroid drugs and the HLA alleles HLA-B*38:02 and HLA-DRB1*08:03. Treatment requires immediate stop of the antithyroid drug and initiation of broad-spectrum antibiotics. Hematopoietic growth factors may be used. Early diagnosis and treatment can prevent the patient from catastrophic event of ATD-induced agranulocytosis.

136

Abstract

PE03

COEXISTENCE OF RESISTANCE TO THYROID HORMONE SYNDROME AND PITUITARY GRANULAR CELL TUMOR IN A TAIWANESE YOUNG LADY, MIMICKING TSH SECRETING TUMOR 1,2

YU-YI LIN, 5CHI-LUNG TSENG, 1,3,4CHUN-JUI HUANG

1

Division of Endocrinology and Metabolism, Department of Medicine,Taipei Veterans General Hospital, Taiwan Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 3Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 4Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; 5Department of Internal Medicine,Taoyuan General Hospital,Ministry of Health and Welfare,Taipei,Taiwan

2

Background: Resistance to thyroid hormone (RTH) syndrome is a rare disorder which presents as high free thyroid hormones with unsuppressed thyroid-stimulating hormone (TSH) secretion and diminished responsiveness to thyroid hormones by target organ. Appropriate diagnosis is crucial to avoid over-treatment with anti-thyroid drugs, radio-iodine ablation, and/or pituitary surgery.

Method: :H SUHVHQWHG WKH ¿UVW FDVH RI 57+ LQ 7DLZDQ ZKR ZDV PLVGLDJQRVHG DV 76+ VHFUHWLQJ tumor but later proved to have pituitary granular cell tumor instead.

Case presentation: A 33-year-old Taiwanese married woman was found to have elevated free T4: QJ G/ QRUPDO DQG 76+ ȝ,8 P/ QRUPDO OHYHOV RQ SUH QDWDO FRXQVHOLQJ for evaluation of palpitation and difficult conception in 2013. Besides mild tachycardia (heart rate: 98 beats per minute), she had no other symptoms and signs of hyperthyroidism. Propylthiouricil was prescribed by her gynecologist and discontinued one year later due to persistence of abnormal thyroid hormone levels under medication. Afterwards, she was referred to an endocrinologist and was told to have central hyperthyroidism based on negative thyroid autoantibodies, moderately enlarged homogenous thyroid glands on thyroid sonography, and a 1.2 cm right pituitary adenoma on sella magnetic resonance imaging (MRI). Endoscopic trans-phenoidal surgery for pituitary tumor removal was performed in May, 2017. Histopathology revealed granular cell tumors that were positive for S-100 protein and TTF-1 but negative for TSH, ACTH, GH and prolactin on immunohistochemical staining. In February 2018, she visited Taipei Veterans General Hospital due to persistence of abnormal thyroid hormone levels (free T4: 2.19 ng/dL; T3: 209 ng/dL, normal: 58-159; total T4 XJ GO QRUPDO 76+ ȝ,8 P/ DIWHU SLWXLWDU\ VXUJHU\ 3RVW RSHUDWLYH VHOOD 05, showed no residual pituitary tumor. After administration of 200 mcg of thyrotropin releasing hormone (TRH) intravenously, exaggerated TSH response was noted, with TSH levels showing 6.0, 24.7, 22.6, DQG ȝ,8 P/ DW DQG PLQXWHV UHVSHFWLYHO\ OHDGLQJ WR WKH GLDJQRVLV RI 57+ '1$ VHTXHQFLQJ RI H[RQV RI WK\URLG KRUPRQH UHFHSWRU ȕ JHQH UHYHDOHG QR PXWDWLRQ $V SUHJQDQF\ ZDV planned, Inderal 5mg thrice daily was used to lower T3 levels in case if a non-RTH fetus exists.

137

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Conclusion: Although rare, RTH should be considered in the differential diagnosis of high thyroid hormone levels with unsuppressed TSH. The presence of a pituitary adenoma does not conclude a TSH secreting tumor, like our case. We suggest careful evaluation with functional and genetic testing prior to initiation of therapy in order to avoid unnecessary surgeries and medications.

A favorable outcome generally follows a diagnosis of RTH. Special consideration needs to be taken in mothers with RTH harboring wild-type fetus.

138

Abstract

PE04

A RARE CASE OF ECTOPIC ADRENOCORTICOTROPIC HORMONE (ACTH) SYNDROME DUE TO THYMIC LARGE CELL NEUROENDOCRINE CARCINOMA PRESENTING AS SEVERE HYPOKALEMIA IN A TAIWANESE MAN 1,2

YU-YI LIN, 1,3LIANG-YU LIN

1

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

Background: Ectopic ACTH syndrome (EAS) represented 5% of Cushing syndrome. EAS is rapid onset, severe, associated with hypercortisolism related life-threatening infections and hypokalemia. In 60% of cases, the tumor is located in intrathoracic organ (lung, bronchus and thymus).

Large cell neuroendocrine tumor (LCNEC) of thymus secreting ACTH is a high grade, aggressive, poor prognosis and only few case reports in literature.

Method: We report a case of thymic LCNEC related EAS, which presented as severe hypokalemia, metabolic alkalosis and muscle weakness.

Case presentation: A 71-year-old man presented with 12-kg weight loss, progressive generalized weakness and bilateral legs edema for two months.He has medical histories of hypertension and diabetes mellitus. Physical examination revealed generalized weakness without Cushingoid appearance. Laboratory examination showed metabolic alkalosis and severe hypokalemia (1.7 mmol/ L, range: 3.4-4.7).Hypokalemia work-up showed high morning ACTH 497 pg/mL (normal: < 46.0), FRUWLVRO ȝJ G/ UDQJH DQG QRUPDO OLPLWV RI RWKHU SLWXLWDU\ KRUPRQHV &XVKLQJ V\QGURPH survey showed lack of ACTH/cortisol circadian rhythm, markedly increased 24h urinary free cortisol H[FUHWLRQ RQ WZR FRQVHFXWLYH GD\V ȝJ /RZ GRVH DQG KLJK GRVH GH[DPHWKDVRQH suppression tests showed non-suppressible. Ovine corticotrophin-releasing hormone stimulation test and desmopressin (DDAVP) test showed ectopic ACTH source. Pituitary MRI revealed negative ¿QGLQJV %LODWHUDO LQIHULRU SHWURVDO VLQXV VDPSOLQJ VKRZHG QR FHQWUDO WR SHULSKHUDO $&7+ JUDGLHQW Ectopic ACTH syndrome was impressed. Etomidate continuous infusion was prescribed.Fournier gangrene of left scrotum occurred during hospitalization and antibiotic and surgical treatment were JLYHQ &KHVW &7 VFDQ UHYHDOHG WLQ\ OREXODWHG QRGXOH LQ OHIW ORZHU OXQJ ¿HOG DQG VRIW WLVVXH QRGXOH LQ prevascular of mediastium. In-111 Octreoscan revealed several nodular lesions with increased In-111 uptake in the paraortic and prevascular region considering neuroendocrine tumor. Anterior mediastinal tumor excision was performed and histopathological report showed large cell neuroendocrine carcinoma of thymus with mitotic count 13/10 HPF and positive immunohistochemical stain for synaptophysin, chromogranin, DD-56, SSTR2 and ACTH. Sandostain LAR injection was administered 139

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

afterward. Unfortunately, tumor progression with hypercortisolemia occurred after 6 months . External radiation and systemic chemotherapy were performed later.

Conclusion: Although rare, Cushing syndrome must be considered in differential diagnosis of hypokalemia like our case, a challenging case of EAS. Early diagnosis and treatment was important to avoid life-threatening infections and metabolic complications. Moreover recurrence free survival with Sandostain LAR alone was only 6 months for LCNEC.

140

Abstract

PE05

PARADOXICAL RESPONSES TO DYNAMIC TESTING FOR CUSHING’S DISEASE: AN UNUSUAL CASE OF LARGE CORTICOTROPH ADENOMA WITH EXTENSIVE LOCAL INVASION 1

HSUAN-WEI LIN, 1SHEAU-FANG PAN, 1YU-YI LIN, 1FANG-YU CHEN, 1,2 CHII-MIN HWU 1

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

Background: Cushing’s disease is most commonly caused by a pituitary microadenoma secreting excessive ACTH. Biochemical responses of corticotroph macroadenoma to dynamic testing are less described in the literature. Here we present the case of a patient with a large and invasive corticotroph adenoma causing Cushing’s disease.

Case: A 67-year-old woman presented to the emergency department with fever and neck swelling.

She was diagnosed with deep neck infection in another hospital and was transferred to our hospital due WR LQFLGHQWDO &7 ¿QGLQJ RI D ODUJH VNXOO EDVH WXPRU H[WHQGLQJ WR WKH QDVDO FDYLWLHV +\SHUFRUWLVROLVP ZDV VXEVHTXHQWO\ GHPRQVWUDWHG DQG FRQ¿UPHG ZLWK PJ GH[DPHWKDVRQH VXSSUHVVLRQ WHVW ([FLVLRQDO biopsy of the intranasal tumor was done along with wound debridement for the deep neck infection.

The pathology of the tumor was compatible with invasive corticotroph adenoma. Dynamic testing revealed cortisol secretion non-suppressible by high dose dexamethasone and not stimulated by ovine corticorelin administration, whereas desmopressin stimulation test was positive. Before definitive surgical treatment of the large adenoma, adequate control of hypercortisolism was achieved with etomidate infusion.

Conclusion: Cushing disease caused by pituitary macroadenomas has biochemical responses distinct from typical one with microadenomas. Such paradoxical diagnostic gap deserves attention to avoid confusion with ectopic ACTH syndrome.

141

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE06

OSTEOPOROSIS IN ADRENAL CUSHING’S SYNDROME: 2 CASE REPORTS YU-LING LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Feng yuan hospital, ministry of health and wealfare, Taiwan, R.O.C.

Background: Osteoporosis is one of the most common complication of Cushing syndrome.

Besides, the reversible nature of osteoporosis is generally accepted, and normalization of bone mineral density following cure of Cushing syndrome could be achieved. Here we report 2 cases of adrenal Cushing’s syndrome and focus on bony complication.

Case 1: A 29-year-old female was referred to the endocrinology OPD due to obesity. PE revealed moon face, but no facial plethora, no acne, no central obesity, easily ecchymosis, increased hair over pre-auricular area and mild hypertension.

Lab: loss diurnal rhythm cortisol 8am/11pm 16.53/16.14 ug/dl; 1mg dexamethasone suppression test: 21(+), with low ACTH: <5/<5; Standard two-day 2 mg test: cortisol 16.55 ug/dl; Na/K: 137/3.7; PA/PRA: corrected ratio 9.8, VMA: 5.78mg/24hrs.

CT: adrenal tumor 28mm(Lt).

Pre-op BMD, spine(9908): T score -0.8, Z score -2.3 Post-op BMD, spine(10302): T score 0.9, Z score 0.0 Then patient received unilateral adrenectomy. Postop F/U 1mg DST: cortisol 0.59 ug/dl. Normal bone mineral density was noted following cure of Cushing’s syndrome Case 2: A 50 y/o male was admitted due to falling down injury with lower legs weakness.

Multiple old rib fractures & T-L spine compression fracture were noted. Past history of Lt adrenal tumor has been noted for yrs but patient refused surgical intervention; DM, HTN F/U at medical center. PE revealed moon face, easily bruise, paper skin.

Lab study: loss diurnal rhythm cortisol 8am/11pm 25.62/29.74 ug/dl;1mg dexamethasone suppression test: 27.60 ug/dl;low ACTH: 5.5/6.0 pg/ml; Na/K: 141/3.4, Ca: 9.1 mg/dl; PA/PRA: corrected ratio 14.79, VMA: 2.59 mg/24hrs(WNL) &7 D VRIW WLVVXH PDVV FP F FDOFL¿FDWLRQV DQG KHWHURJHQHRXV HQKDQFHPHQW DW /W VXSUD UHQDO region, a left adrenal tumor /c lung and liver metastasis is considered.

L spine: multiple compression fracture of the T-L vertebral body- T11, L2, and L4.

BMD, Lt femoral neck, T score -3.1, Z score -2.5; BMD, Rt femoral neck, T score -3.0, Z socre -2.3 Conclusion: Cushing syndrome comprised the S/S associated with prolonged exposure to inappropriately elevated levels of glucocorticoid. Glucocorticoids inhibit osteoblast function which 142

Abstract

account for the osteopenia and osteoporosis. Besides, glucocorticoids also induce negative calcium balance by inhibiting intestinal calcium absorption and increasing renal calcium excretion and VXEVHTXHQW FRPSOLFDWLRQ RI IUDFWXUH (DUO\ LGHQWL¿FDWLRQ DQG LQWHUYHQWLRQ RI &XVKLQJ¶V V\QGURPH LV EHQH¿W WR WKH ORQJ WHUP RXWFRPH

143

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE07

A CASE REPORT OF SEVERE HYPOTHYROIDISM PRESENTING WITH ACUTE CONSCIOUS CHANGE AND SEIZURES JUI-HSIANG LI, YOUCHENG CHEN, SU-HUEY LO Department of Internal Medicine Tao-Yuan General Hospital

Brief history: A 38-year-old female had sudden onset of agitation with attack tendency. She was sent to our ER for evaluation and repeated generalized tonic-clonic seizure attack was observed duration about 30 seconds frequently. She was admission and seizure attack was still noted. Though, the EEG showed normal cortical function. The brain MRI revealed post-ictal right hemispheric brain swelling. The laboratory showed TSH = 214,Free T4 = 0.23 compatible with primary Hypothyroidism. :H JDYH HOWUR[LQ 32 4' 7KH VHL]XUH DWWDFN SURJUHVVLYHO\ LPSURYHG 6KH WKHQ GLVFKDUJHG Discussion: Thyroid hormones act in the brain where they play an essential role in fetal and post-natal brain development as well as the maintenance of adult brain function. In addition, thyroid hormone promotes CNS repair, as it has been demonstrated that CNS re-myelination is dependent on these hormones. Hypothyroidism is insufficiency of thyroid gland to produce thyroid hormone WR VDWLVI\ WKH UHTXLUHPHQW RI SHULSKHUDO WLVVXHV 'H¿FLHQF\ RI WK\URLG KRUPRQH FHUHEUDO EORRG ÀRZ LV UHGXFHG EXW FHUHEUDO R[\JHQ FRQVXPSWLRQ LV XVXDO ,Q VHYHUH FDVHV GHFUHDVH FHUHEUDO EORRG ÀRZ may lead to cerebral hypoxia and predispose to confusion attacks and syncope. Psychiatric disorders are common and are usually of paranoid or depressive type and may induce agitation (myxedema madness). Epileptic seizures have been reported and tend to occur in myxedema crisis. The cause of seizure activity in hypothyroidism is unknown. It may be due to cerebral edema secondary to expansion of extracellular fluid volume. Inappropriate antidiurectic hormone(ADH) secretion, hyponatremia and hypoventilation with postanoxic encephalopathy maybe relate to this condition and further precipitate seizure activity. Management of myxedema crisis involves replacement of thyroid hormone with correcting predisposing factor and supportive care. Prior to thyroxine therapy, JOXFRFRUWLFRLG UHSODFHPHQW VKRXOG EH FRQVLGHUHG ¿UVW GXH WR SRVVLELOLW\ RI DGUHQDO LQVXI¿FLHQF\ DQG increasing cortisol clearance.

144

Abstract

PE08

THYROID STORM WITH ECMO SUPPORT IN A 41-YEAR-OLD WOMAN: A CASE REPORT 1

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

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

Introduction: Thyroid storm is a life-threatening condition which have an exaggeration of the usual symptoms of hyperthyroidism. The clinical presentation includes fever, tachycardia, hypertension, and neurological and GI abnormalities.

Rapid diagnosis is important, because cardiogenic shock or multiple organ failure may occur if left untreated in some patients. Extracorporeal membrane oxygenation (ECMO) provide the last chance in patient with critical patients.

Case: A 41-year-old female presented with progressive shortness of breath for 2 days. She had underlying disease of Graves’ disease under regular medication control. She hold the anti-thyroid drug by herself since 2 weeks ago. Then progressive dyspnea, poor appetite, and diarrhea occurred.

6KH ZDV VHQW WR RXU HPHUJHQF\ GHSDUWPHQW IRU KHOS $WULDO ¿EULOODWLRQ ZLWK UDSLG YHQWULFXODU UDWH DQG acute pulmonary edema were noted. Intubation was arranged due to hypoxemic respiratory failure.

Propylthiouracil (PTU), Lugol’s solution, and systemic steroid were administered. However, refractory hypotension developed despite aggressive fluid challenge and maximal dose of vessel-constriction agent. Thyroid storm with acute heart failure and cardiogenic shock were suspected. After discussion with her family, ECMO was used. CVVHD was also arranged due to acute kidney injury with oligouria. Fortunately, the vital sign became stable gradually, and ECMO was removed followed by mechanical ventilation weaning successfully.

145

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE09

LONG-TERM OUTCOME AND PROGNOSTIC FACTORS OF SINGLE DOSE RADIOIODINE THERAPY IN PATIENTS WITH GRAVES’ DISEASE 1

YI-TING YANG, 1PEI-WEN WANG, 1JUNG-FU CHEN, 1SHIH-CHEN TUNG, 1 MING-CHUN KUO, 1SHAO-WEN WENG, 1CHEN-KAI CHOU, 1FENG-CHIH SHEN, 1 CHIH-MIN CHANG, 1CHIA-JEN TSAI, 1CHENG-FENG TSAO 1

Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: There are few domestic studies regarding the long-term outcome of radioiodine(RAI) therapy in patients with Graves’ disease(GD). The aim of this study is to evaluate WKH FOLQLFDO HI¿FDF\ DQG IDFWRUV LQÀXHQFLQJ WKH VXFFHVV RI RQH GRVH UDGLRLRGLQH WKHUDS\ LQ 7DLZDQHVH patients with GD. Methods: This is a retrospective clinical study. There were 424 patients who received RAI treatment for hyperthyroidism between 1989 and 2016 in Kaohsiung Chang Gung Memorial Hospital.

Excluding those with toxic adenoma, loss of follow-up, thyroidectomy or 2nd dose of RAI within 3 years after RAI therapy and whose charts were unavailable for review, totally 182 patients with GD ZHUH LQFOXGHG IRU DQDO\VLV (X RU K\SRWK\URLG DIWHU 5$, WKHUDS\ ZHUH GH¿QHG DV VXFFHVVIXO JURXS 7KH LQÀXHQFH IDFWRUV LQFOXGHG DJH JHQGHU 5$, GRVH JRLWHU VL]H WK\URLG IXQFWLRQ WHVW DQG WLWHUV RI thyroid antibodies. Kaplan-Meier curve, cox-regression model and ROC curve were used for statistical analysis.

Results: Loss of regular follow-up was found in 31.1% (108/347) of the patients. Among the 182 SDWLHQWV EHLQJ DQDO\]HG PRVW GLG QRW FKRRVH 5$, DV ¿UVW FKRLFH KDG KLVWRU\ RI UHFXUUHQW hyperthyroidism after thyroidectomy or prolonged drug therapy, 29 suffered from severe adverse antithyroid drug reaction. Most (75.8%) were females, and the mean age was 46.4 ± 13.8years. The mean RAI dose was 8.2 ± 3.3mCi(range 3-20mCi). The mean follow-up period was 108.8 ± 79.3 PRQWKV ZLWK D VXFFHVVIXO UDWH RI *RLWHU VL]H ZDV WKH RQO\ IDFWRU VLJQL¿FDQWO\ GLIIHUHQW EHWZHHQ success and failure groups. Patients with grade 0-2 goiter had higher successful rate than patients with grade 3 goiter (p value = 0.002,HR = 2.02, 95%CI = 1.28-3.19). But if an early regression of grade 3 goiter to grade 0-2 in 3 months after RAI therapy, the successful rate was not inferior to those with initial grade 0-2 goiter. ROC curve revealed that the best timing to evaluate treatment result and the overall cut-off point was 27.5 months, while that for patients with grade 0-2 and grade 3 goiters was 11 months and 39months, respectively.

Conclusions: ,Q WKLV UHDO ZRUOG VWXG\ SDWLHQWV ZLWK *' LQ 7DLZDQ GR QRW SUHIHU 5$, DV WKHLU ¿UVW choice of therapy. Further, regular follow-up after RAI therapy should be emphasized. ,Q RXU VHULHV JRLWHU VL]H LV WKH RQO\ IDFWRU LQÀXHQFLQJ WKH HIIHFWV RI 5$, WKHUDS\ IRU *' 146

Abstract

PE10

NIVOLUMAB INDUCED THYROIDITIS IN PATIENT WITH HEPATOCELLULAR CARCINOMA - A CASE REPORT 1

CHIH-CHEN WANG, 1HAO-CHANG HUNG, 1JING-HAN LIN, 1CHUN-CHUNG LIN, 1 HORNG-YIH OU 1

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

A 59-year-old man initially visited our outpatient department because of sudden onset of right upper quadrant abdominal pain, and abdominal CT showed bilateral hepatic tumors. Liver biopsy confirmed the diagnosis of hepatocellular carcinoma. Since then, the patient received seven times of treatment course of TACE with Doxorubicin, but MRI still showed liver tumor recurrence.

We then started HAIC with Cisplatin and Doxorubicin for three times. However, abdominal MRI still revealed progression of residual liver tumors. Due to poor response of treatment, we started Nivolumab therapy(3 mg/kg). After two courses, the patient reported tachycardia, and new onset of paroxysmal atrial fibrillation with rapid ventricular response was found. Thyroid function tests showed TSH: < 0.03 uU/ml and Free T4: 2.98 ng/dl. Thyroid autoimmunity showed microsomal Ab: positive, thyroglobulin Ab: positive, anti-mitochondrial Ab: 1:10(-) and Anti-TSH receptor: < 0.3(U/ L). Therefore, we empirically prescribed Methimazole 5 mg b.i.d by mouth since 2018/10/19 for suspicious thyrotoxicosis. After 1 week of the treatment, palpiatation was improved and laboratory data on 2018/10/24 showed Free T4: 1.72 (ng/dl)/T3: 103.75 (ng/dl). We adjusted Methimazole to 5mg q.d and kept it for one more month. Laboratory data on 2018/11/13 showed: TSH: 33.05(uU/ml)/Free 7 QJ GO 7 QJ GO DQG ZH ¿QDOO\ FHDVHG 0HWKLPD]ROH XVH

147

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE11

LENVATINIB AS SALVAGE TREATMENT IN RAI-REFRACTORY DTC PATIENTS WITH PRIOR TYROSINE KINASE INHIBITOR FAILURE: A SMALL CASE SERIES REPORT 1

DANIEL HY SHEN, 2MING-LANG SHIH, 3REN-HUA YEH, 4SHAO-CHENG LIU, 1 LI-FAN LIN, 1CHENG-HAN HO, 1YUEH LEE, 1CHENG-YI CHENG 1

Department of Nuclear Medicine and PET Center, Tri-Service General Hospital, Taiwan, R.O.C.; 2Department of Surgery, Tri-Service General Hospital, Taiwan, R.O.C.; 3Department of Internal Medicine, Tri-Service General Hospital, Taiwan, R.O.C; 4Department of Head & Neck Surgery, Tri-Service General Hospital, Taiwan, R.O.C

Backgrounds: When differentiate thyroid cancer (DTC) becomes RAI-refractory (RAI-R), tyrosine kinase inhibitors (TKIs) such as Sorafenib and Lenvatinib might be useful to control the disease. On the basis of two phase III clinical trials (DECISION and SELECT) showing good therapeutic response and enhanced progression-free survival of both TKIs, both agents have been approved for treatment of RAI-R DTCs but, indeed, the earlier emergence of Sorafenib renders most such patients probably receive 6RUDIHQLE ¿UVW 7KHUH LV QR GLUHFW FRPSDULVRQ RI ERWK DJHQWV LQ PDQDJLQJ 5$, 5 '7& EXW /HQYDWLQLE seems one of the choices for subsequent management in such patients with Sorafenib failure. Our study aims to investigate the usefulness of Lenvatinib as salvage treatment.

Methods: We retrospectively evaluated patients (N = 15) with RAI-R DTCs ever treated with Sorafenib first and then switched to Lenvatinib due to tumor progression in our institute. Tumor response was assessed by RECIST criteria, change of serum thyroglobulin (Tg) after treatment, and change of FDG avidity in terms of SUVmax of main tumor lesion(s) were measured. The frequency of drug-related adverse effects (AEs) graded by CTCAE v.4 were also analyzed.

Results: Twelve (80%) of 15 RAI-R DTC patients with Sorafenib failure showed good response to Lenvatinib treatment including stable disease (n = 3) and partial response (n = 9) with enduring response of median of 12 months. There is a dramatic drop of serum Tg in Lenvatinib responders on initial intervention showing -45 to -98% of change during 3-6 months after treatment. There is a marked change of lesional FDG avidity with -53% to -83% of change after at least 10 months of treatment. The drug-related AEs were recorded from all these RAI-R DTC patients (N = 15) including hypertension (n = 9), proteinuria (n = 6), fatigue (n = 6), diarrhea (n = 5), dermatitis or hair loss (n = 5) and sporadic ones like stomatitis, hoarseness, hypocalcemia, acute cholecystitis (n = 1, death), tumor bleeding (n = 1, death), open wound with necrosis (n = 1, death). Also some serum biochemical abnormalities like elevated TSH, AST, ALT, creatinine or amylase level were noted occasionally.

Conclusion: From our study, the use of Lenvatinib as salvage treatment for RAI-R DTC cases with Sorafenib failure are manifested by greatly reduced serum Tg and tumor FDG uptake. However, the management of common AEs as well as to prevent fetal AEs is needed. For those who show proteinuria 148

Abstract

or serum biochemical abnormalities, further study to understand the long-term effect is warranted.

PE12

SUBACUTE THYROIDITIS WITH HYPOPARATHYROIDISM - A CASE REPORT 1

SHU-HSUAN HUANG, 2HAO-CHANG HUNG, 2YE-FONG DU, 2HORNG-YIH OU

1

Department of Internal Medicine, National Cheng Kung University Hospital, 2Division of Endocrinology and Metabolism, National Cheng Kung University Hospital

Subacute thyroiditis is usually a self-limited disease without complications, and hypothyroidism becomes permanent in rare cases. We report a case of subacute thyroiditis with hypoparathyroidism.

A 38-year-old woman presented with recurrent epigastric pain followed by muscle cramps and carpopedal spasms, together with chest tightness and anxiety. Laboratory tests showed severe hypocalcemia, hyperphosphatemia, hypomagnesemia, and low-normal iPTH level. These presentations were preceded by an episode of fever with upper respiratory tract symptoms one month ago. Thyroid function tests showed thyrotoxicosis with positive anti-thyroid peroxidase antibody and antithyroglobulin Ab. Thyroid ultrasonography demonstrated bilateral thyroid nodules less than 1 cm, and the I131 thyroid uptake/scan suspected subacute thyroiditis. Her symptoms subsided after correction of serum calcium level. She received calcium carbonate, calcitriol for primary hypoparathyroidism, and thyroxine support for hypothyroid phase one year later.

149

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE13

CRIBRIFORM-MORULAR VARIANT OF PAPILLARY THYROID CARCINOMA: A CASE REPORT AND REVIEW OF THE LITERATURE 1

YUNG-NIEN CHEN, 2SHUN-CHEN HUANG, 1JUNG-FU CHEN, 1CHEN-KAI CHOU

1

Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.; 2Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, R.O.C.

Background: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare but distinct histological subtype of papillary thyroid carcinoma (PTC) associated with familial adenomatous polyposis(FAP). FAP is an autosomal dominant cancer predisposition syndrome characterized by the progressive development of multiple colorectal adenomatous polyps and an increased risk of colorectal carcinoma.

Methods: :H UHSRUW FOLQLFDO IHDWXUHV DQG LPDJLQJ ¿QGLQJV RI D WHHQ DJHG JLUO ZLWK HDUO\ WK\URLG cancer histologically diagnosed with CMV-PTC and colon polyps.

Results: A 19-year-old girl presented to the endocrine clinic with palpable thyroid nodules of six months duration. Both of her grandmothers and two aunts had unknown thyroid disease. Fineneedle aspiration of thyroid was compatible with Bethesda category V: suspicious for malignancy.

Because of her family history of FAP, colonoscopy was arranged and revealed large bowel polyposis.

She underwent total thyroidectomy which revealed CMV-PTC. Histology was characterized by a prominent cribriform pattern of growth with interspersed cell clustered arranged as morules.

Immunohistochemical (IHC) staining for CMV-PTC cells reveal beta-catenin in both the nuclei and cytoplasm, which is the key feature of this subtype.

Conclusion: Patients with CMV-PTC have distinctive clinical, pathological pattern and elevated risk of colorectal cancer when compared to conventional papillary thyroid carcinoma. Young thyroid cancer patients with strong family history of thyroid or colorectal cancer should be evaluated the possibility of CMV-PTC by IHC staining of beta-catenin. Due to its strong connection with FAP syndrome, further colonoscopy and genetic study of the APC gene sequencing should be also considered.

Keywords: Papillary thyroid carcinoma, Cribriform morular variant, Familial adenoatous polyposis

150

Abstract

PE14

DOUBLE PRIMARY CANCERS IN PATIENTS WITH THYROID CANCER: A RETROSPECTIVE ANALYSIS REPORT IN SOUTHERN TAIWAN 1

SHU-TING WU, 2SHUN-YU CHI, 1JUNG-FU CHEN, 1CHEN-KAI CHOU

1

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

Background: Thyroid cancer is the most common endocrine cancer. Thyroid cancer survivors had an increasing risk of double primary cancers. Patient with double primary cancers in the setting of thyroid cancer had worse prognosis. The aim of this study was to investigate the clinicopathological characteristics, sex differences in cancer incidence trends, and survival of these double primary FDQFHUV :H DOVR DVVHVVHG WKH ULVN RI VHFRQG SULPDU\ FDQFHU DIWHU VSHFL¿F WUHDWPHQWV IRU HDFK FDQFHU such as radioactive iodine treatment for thyroid cancer and radiation therapy for breast cancer.

Methods: Between 2013 and 2017, a total of 935 thyroid cancer patients who had long-term follow-up at Kaohsiung Chang Gung Memorial Hospital in Taiwan were retrospectively reviewed.

Clinical data were obtained from the medical records. Those with double primary cancers were FDWHJRUL]HG DV V\QFKURQRXV ZLWKLQ PRQWKV RI ¿UVW SULPDU\ WXPRU RU PHWDFKURQRXV DIWHU PRQWKV IURP WKH GLDJQRVLV RI WKH ¿UVW SULPDU\ WXPRU

Results: A total of 84 patients with double primary cancers in the setting of thyroid carcinoma were identified from the 935 thyroid cancer patients, giving a prevalence rate of 9% at our center.

The mean age of diagnosis with double primary cancers was 58.3 ± 10.6 years. There was a female preponderance (26 males and 58 females). The most common site of second primary cancer was the head and neck in men and the breast in women. Of the 84 double primary cancers, 26 were synchronous in nature and 58 were metachronous. Among synchronous malignancies (26/44 patients), H&N tumors were the most commonly associated. In further analysis, 12 patients had incidental WK\URLG FDQFHU DV VHFRQG SULPDU\ FDQFHU ZKLFK ZDV XQVXVSHFWHG LGHQWL¿HG E\ )'* 3(7 RU &7 IRU WKH ¿UVW SULPDU\ FDQFHU IROORZ XS Conclusions: There has been an increase in the number of patients diagnosed with double primary cancers with thyroid cancer. This trend can be due to prolonged life span, the increase survival rate of cancer patients, and better diagnostic techniques. The relationship between the double primary cancers has been investigated but the exact attributive factors and pathophysiology still controversial.

Greater awareness of the increasing prevalence of multiple primary cancers in our clinical practice is required among both cancer patients and clinical physicians.

151

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE15

CLINICAL EXPERIENCE OF TSHOMA IN CHANG-GUNG MEMORIAL HOSPITAL 1

YU-LING LU, 1MIAO-JHEN LIOU, 1CHENG-WEI 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.

Background: Thyroid-stimulating hormone secreting pituitary adenoma (TSHoma) is a rare cause of of hyperthyroidism. Here we report 3 cases of TSHoma diagnosed and treated in a referral medical center.

Methods: With the finding of an abnormally elevated TSH level, 3 cases of TSHoma were FRQ¿UPHG E\ LPDJH VWXG\ DQG KLVWRSDWKRORJLFDO DQDO\VLV 7KH FOLQLFDO FRXUVH WUHDWPHQW DQG RXWFRPH of 3 TSHoma cases were retrospectively analyzed.

Results: The demographic characteristics of 3 TSHomas were illustrated in Tab. 1. All the 3 patients had high free T4 (fT4) and normal to high TSH levels initially. Two of them received TRH stimulation test with blunted TSH response. For suspected TSH secreting pituitary tumor, all patients underwent sella MRI/CT, and pituitary macro- or micro-adenoma were disclosed with positive stain for multi-hormones. All patients received trans-sphenoidal surgery (TSS) to resect/biopsy of the pituitary adenoma. The situation after TSS was different, hypothyroid developed initially and returned to euthyroid in case 1 with residual tiny tumor. High fT4 and normal TSH level initially, then became euthyroid and adrenal insufficiency in case 2 with residual macroadenoma. Persistent high fT4 with low-normal TSH was found in case 3 although sella MRI showed absence of residual tumor.

Euthyroidism was achieved after bromocriptine (BMC) treatment, and the patient eventually received WRWDO WK\URLGHFWRP\ EHFDXVH WKH LQFLGHQWDO ¿QGLQJ RI SDSLOODU\ PLFURFDUFLQRPD Conclusions: TSHoma should be taken into consideration in hyperthyroid patients with normal to high TSH. TRH stimulation test may not differentiate primary from secondary hyperthyroidism and/or resistance to thyroid hormone syndrome. The tumor size was correlated with time lag to a definite diagnosis of TSHoma, but not correlated with the use of anti-thyroid drug (ATD). In the two macroadenomas (cases 1 and 2) with growth hormone (GH) and prolactin (PRL) co-secretion, biochemical remission was achieved even with postoperative residual tumors. In the folliclestimulating hormone (FSH) and luteinizing hormone (LH) co-secreting microadenoma (case 3), persistently elevated TSH was found postoperatively without radiological evidence of residual tumor (although a response to BMC was observed). Thus, the clinical course and outcome of TSHomas were histologic type rather than tumor size correlated. Finally, papillary microcarcinoma may develop in TSHoma patients due to long term TSH overstimulation.

152

Abstract

PE16

THYROID PAPILLARY CARCINOMA ARISING IN ECTOPIC THYROID TISSUE WITHIN RIGHT SUPRACLAVICULAR NECK AREA 1

YIN-HUEI CHEN, 1CHING-CHUNG CHANG, 1GIA-YIN KUO, 2CHUN-CHIEH YEH, 4 CHEN-YUAN LIN, 3YEN-NIEN LIN, 1CHWEN-TZUEI CHANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital; Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 3Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital; 4Division of Hematology and Oncology, Department of Medicine, China Medical University Hospital, Taiwan

2

Background: More than 99% of thyroid cancers arise eutopically within the thyroid gland.

Thyroid ectopy has a reported prevalence of approximately 1 in 10,000. Lingual, sublingual, thyroglossal, laryngotracheal, and lateral cervical are the most frequent origins of ectopic thyroid tissue. Ectopic thyroid tissue can be subject to the same pathological processes as normal eutopic thyroid tissue such as inflammation, hyperplasia, and tumorigenesis. Notably, regarding malignant lesions of the ectopic thyroid, it may be extremely difficult to distinguish primary neoplastic involvement of ectopic thyroid tissue from a cervical lymph node metastasis.

Case presentation: A 32-years-old female was incidentally found to have right neck mass during health examination. She was referred to endocrinologist and physical examination was remarkable for one elastic mass, measured 3.0cm in right neck. Thyroid sonography disclosed a KHWHURJHQRXV K\SRYDVFXODU K\SRHFKRLF OHVLRQ ZLWK PP LQ ULJKW VLGH $OWKRXJK ¿QH QHHG aspiration cytology showed no evidence of malignancy, she was referred to surgeon for malignant like sonographic appearance. The patient underwent a right total thyroidectomy and left subtotal thyroidectomy. Histology showed a multifocal papillary carcinoma with follicular variant. She then received further left total thyroidectomy and a subsequent I131 ablation.

Conclusion: An ectopic thyroid cancer should be considered in the differential diagnosis of a pathological mass in the neck. Treatment of ectopic cervical thyroid cancer is based predominantly on the surgical excision of the malignant lesion. Management strategies, including performance of total thyroidectomy, neck dissection, and treatment with radioiodine, should be based on individualized risk VWUDWL¿FDWLRQ

153

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE17

UTILIZATION OF RADIOFREQUENCY ABLATION FOR TREATMENT OF LOCALLY RECURRENT PAPILLARY THYROID CANCER WITH METASTATIC LYMPH NODE- A CASE SERIES AND LITERATURE REVIEW 1

WEN-CHIEH CHEN, 2WEI-CHE LIN, 1JUNG-FU CHEN, 1CHEN-KAI CHOU

1

Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Surgery is the standard management for recurrence of differentiated thyroid FDUFLQRPD ZKLFK PD\ EH FKDOOHQJLQJ GXH WR SRVW RSHUDWLYH QRUPDO WLVVXH SODQH GLVWRUWLRQ DQG ¿EURVLV and for those with high surgical risk or refuse surgery. Considering the above condition, radiofrequency ablation (RFA) has been suggested to be a safe and well-tolerated alternative by American Thyroid Association (ATA). In the mean time, the efficacy of RFA for lymph node metastasis refractory to radioiodine therapy is not fully understood.

Methods: We present three cases of treatment of recurrent tumor or metastatic lymph node treated with the use of RFA session(s) in patient with previous history of total thyroidectomy and neck lymph node dissection for papillary thyroid carcinoma.

Results: We present case 1 as a 63-year-old male found a mediastinal mass with size of FP DQG UHFHLYHG PHGLDVWLQDO WXPRU H[FLVLRQ DQG WRWDO WK\URLGHFWRP\ ZLWK PRGL¿HG UDGLFDO QHFN dissection, with negative surgical margins (R0). The pathological result yielded papillary carcinoma (PTC), pT4aN1bM0 (AJCC, 7th edition), stage IVa. He received radioiodine therapy twice with biochemical incomplete (accumulated dose 240 mCi, stimulated thyroglobulin was 18.9 and 10.2 ng/ ml, separately). Two years later a RAI-refractory lesion in thyroid bed was noted. The patient received 5)$ WZLFH DQG VLJQL¿FDQW LPSURYHPHQW RI 7J OHYHO ZDV QRWHG IURP WR QJ PO PRQWKV after the second RFA session). Shrinkage of tumor size (from 0.7 to 0.6cm) on US was also noted.

Case 2 is a 42-year-old female with PTC (AJCC 7th pT4aN1b), post total thyroidectomy with lymph node dissection. For metastatic papillary carcinoma, she took radioiodine therapy (twice, accumulated 250mCi); elevated Tg level remained and refractory to RAI was suspected by PET. Therefore, she received RFA session twice (Tg 79.2 ng/ml before RFA). Shrinkage of tumor size over left thyroid bed, isthmus, left neck level III and right paratracheal space was noted with improved Tg level to 40.7 ng/ml at 1 month after RFA. For one newly-found right supraclavicular metastatic lesion, repeated RFA or surgical intervention may be needed.

Case 3 is a 56-year-old male with PTC post total thyroidectomy and radioiodine therapy at other hospital. During regular follow-up, one new nodule with size of 9.1x3.3x7.6 mm in left paratracheal region with suspicion of malignancy on biopsy was noted. He then received RFA session in Nov, 2017 154

Abstract

DQG ZDV WROHUDWHG LW ZHOO )ROORZHG 86 UHYHDOHG GLI¿FXOW WR LGHQWLI\ RI DEODWHG OHVLRQ DW PRQWKV ODWHU Conclusions: The RFA session can lead to biochemical (Case 1, 2) or structural (Case 1, 3) UHPLVVLRQ DW PRQWKV DIWHU 5)$ ZLWKRXW VSHFL¿F FRPSOLFDWLRQ )RU WKRVH ZLWK GLI¿FXOW DSSURDFKHG tumor location, surgical intervention is still the standard management. In conclusion, radiofrequency ablation is safe and well-tolerated, with a low incidence of complication, and is an appropriate method for those not suitable or refuse of operation.

155

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE18

ECTOPIC PARATHYROID ADENOMA: A CASE REPORT 1

CHIEH CHANG, 1NING-CHUN WENG, 2YI-SUN YANG, 2EDY KORNELIUS, 3WEISHIN CHEN, 2SHIH-CHAN LO, 2CHIEN-NING HUANG 1

Medical School, Chung-Shan Medical Unversity, Taiwan Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Shan Medical University Hospital, Taiwan 3 Department of Surgery, Taichung General Veterans Hospital, Taiwan 2

Ectopic parathyroid glands result from aberrant migration during early stages of development and lack of successful identification may lead to lack of success in parathyroid surgery. They constitute a common etiology of persistent or recurrent hyperparathyroidism, when they are missed at initial diagnosis. We describe a case of a 35-year-old male presenting with ankylosing spondylitis, incidentally found to have hypercalcemia (calcium level 13.8 mg/dl) during routine follow up of ankylosing spondylitis. Subsequent evaluation revealed elevated parathyroid hormone level (1675 pg/ ml). Suspecting hyperparathyroidism, Technetium-99 (Tc-99m) sestamibi scan was done, revealing an abnormal persistent hot spot at right thoracic inlet: high right paratracheal region behind right sternoclavicular joint, suspected an ectopic parathyroid adenoma. CT scan of neck revealed a 3.1 cm nodular lesion over right upper paratrachea region. The mass was surgically excised and it was diagnosed as a parathyroid adenoma. Serum calcium and parathyroid hormone level decreased DIWHU VXUJHU\ 7KHUH ZDV QR VLJQV RI PHWDVWDVLV DQG WKH SDWKRORJ\ FRQ¿UPHG WKH PDVV WR EH EHQLJQ Ectopic inferior parathyroid glands are most frequently found in the anterior mediastinum, while the most common position for ectopic superior parathyroids is the tracheoesophageal groove and UHWURHVRSKDJHDO UHJLRQ 1HFN XOWUDVRXQG DQG P7F 6HVWDPLEL VFDQ DUH ¿UVW OLQH LPDJLQJ PRGDOLWLHV After successful localization, assisted by rapid parathyroid hormone measurement postoperatively, VLJQL¿FDQWO\ LPSURYHV VXUJLFDO RXWFRPHV LQ SDWLHQWV ZLWK HFWRSLF SDUDWK\URLG DGHQRPDV

156

Abstract

PE19

OVERVIEW OF STIFF PERSON SYNDROME AND VARIANTS PROVIDE AN INSIGHT INTO THE ANTI-GAD ANTIBODY TITERS AND OTHER AUTOIMMUNITY DISEASES 1

YI-YIN LEE, 1YI-WEN CHEN, 1CHIH-CHING WANG, 1SZU-TAH CHEN

1

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

Background: Stiff person syndrome (SPS) is a rare neurological disorder identified as an autoimmune or paraneoplastic syndrome with frequent positive serum anti-glutamic acid decarboxylase (GAD) antibodies (anti-GAD Ab). GAD is the enzyme that catalyzes the production of Ȗ DPLQREXW\ULF DFLG *$%$ D PDMRU LQKLELWRU\ QHXURWUDQVPLWWHU RI WKH FHQWUDO QHUYRXV V\VWHP 6LQFH that anti-GAD Ab are also detected in up to 80% of early stage type 1 diabetes mellitus (T1DM), it is QRW VXUSULVLQJ WR ¿QG DVVRFLDWLRQ RI 7 '0 ZLWK 636 7KH SXUSRVH RI WKLV VWXG\ ZDV WR VSHFLI\ WKH OLQN of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects.

Methods: This retrospective study was approved by the institutional review board of Chang Gung memorial hospital (CGMH). Patients diagnosed as SPS in CGMH since January 2001 to June 2018 were enrolled. The clinical presentation, coexisting diseases associated with anti-GAD Ab (especially T1DM and autoimmune thyroid disease, AIT), and/or other immunological (anti-nuclear antibodies, ANA) abnormalities were verified. Co-existing malignancies, major complications and medical treatment were also recorded. Anti-GAD Ab were measured by an enzyme-linked immunosorbent assay (ELISA) kit with the cut-off value of <5 U/ml.

Results: A total of 14 SPS patients (5 female and 9 male) were enrolled. The median age at symptom onset was 42.3 (19.1-84.0) years with median follow-up duration of 8.0 years. 11 patients had stiffness and painful spasms in axial muscles with progress to proximal leg muscles, 3 patients involved only bilateral lower extremities. Some patients showed symmetric spine deformity, hyperlordotic spine with limited flexibility. Nine of these patients received anti-GAD Ab tests, and among the 3 seropositive patients, 2 were concomitant with T1DM, and the other one has co-existing AIT. Another T1DM patient was diagnosed and followed-up at other hospital without available antiGAD Ab data. In the other patients with seronegative anti-GAD Ab, 1 Sjögren syndrome (ANA positive), 1 type 2 DM (onset at age 39 with insulin injection since age 49 but with normal c-peptide level) and 2 associated neoplasms (1 lung cancer and 1 thymoma) were documented.

Conclusions: Despite that T1DM and SPS are both autoimmune diseases characterized with positive anti-GAD Ab, the concurrence of SPS, T1DM and/or AIT remains sparse. The titers of anti-GAD Ab in those with SPS are much higher than those in T1 DM alone, often with a 100- to 500-fold difference. By recognizing the association of SPS with autoimmune diseases and/or malignancy, physicians may predict the development of T1DM and prevent its co-morbidities in SPS patients, and vice versa.

157

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE20

TRANSFORMATION OF NONFUNCTIONAL PANCREATIC NEUROENDOCRINE TUMOR INTO FUNCTIONAL PANCREATIC NEUROENDOCRINE TUMOR (MALIGNANT INSULINOMA): THREE CASES FROM A SINGLE TERTIARY CENTER 1,2

SHEAU-FANG PAN, 1,3LIANG-YU LIN

1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Internal Medicine, City Hospital of Yang-Ming Campus, Taipei, Taiwan; 3 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

This report presented three patients of nonfunctional pancreatic neuroendocrine tumor (PNET), their initial clinical presentation with mass effects and their pathologic findings. They denied any symptom or sign of hypoglycemia. Most importantly, all three patients developed hyperinsulinemic hypoglycemia which lead to the diagnosis of functional pancreatic neuroendocrine tumor after different treatments.

7KHVH WKUHH SDWLHQWV ZHUH LQ WKHLU ODWH ¿IWK DQG VL[WK GHFDGH ZKHQ ¿UVW SUHVHQWHG ZLWK DEGRPLQDO SDLQ 7KHLU ODE GDWD VKRZHG WKH LQFUHDVH LQ QHXURQ VSHFL¿F HQRODVH 16( DQG QRUPDO JOXFRVH OHYHO while other endocrine profiles were within normal limits. Their CT scan of abdomen all reported pancreatic tail tumor with liver metastasis, with one patient also having spleen invasion and another patient having lymphadenopathy. They received different systemic treatments for PNETs. But they all had tumor recurrence and developed severe symptomatic hypoglycemia later (form 1 year 3 months to 4 years 9 months) with lab data proven hyperinsulinemic hypoglycemia a. These data suggest that these three patient with initially diagnosis of nonfunctional PNET had later transformed into functional pancreatic neuroendocrine tumors. This might lead further evaluations for manipulating beta cell function.

158

Abstract

PE21

PROPYLTHIOURACIL FROM RECTAL ADMINISTRATION IN HYPERTHYROID PATIENT 1

SHENG-PANG HSU, 1CHING-CHU CHEN

1

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

Case Report: This 61-year-old retired male patient was admitted to MICU due to massive oral bleeding with conscious change on 2018/09/30. He was a case of left buccal SCC s/p operation (composite resection and marginal mandibulectomy and inferior maxillectomy and left SND + free ÀDS UHFRQVWUXFWLRQ RQ DQG UDGLDWLRQ WKHUDS\ 8QIRUWXQDWHO\ WXPRU UHFXUUHQFHV DQG KH ZDV treated by palliative chemotherapy and target (cetuximab)therapy recently.

In order to control the massive oral bleeding, transarterial embolization (TAE) which showed acute blow-out of the right proximal external carotid artery post selective transarterial embolization.

After TAE .The bleeding was controlled and Hemoglobin showed stable(6.9 g/dL-- > 10.7 g/dL).

Amiodarone IV infusion was given for Atrial fibrillation with RVR (HR:140-160) in the beginning of MICU hospitalization . Thyroid function showed thyrotoxicosis related to Graves’ disease ( TSH < 0.005 uIU/mL, free T4:3.45 ng/dL, Anti-TPO:319 IU/mL, Anti-thyroglobulin antibody: 28.7 IU/mL, TSH-recepter antibody: 32.8%). However, patient has no NG tube due to high risk of tumor bleeding. The General Surgeon planned to perform gastrostomy after relative stable hemodynamic VWDWXV ,Q WKLV FHUWDLQ FDVH ZH XVHG SURS\OWKLRXUDFLO PJ LQ PO GLVWLOOHG ZDWHU 4 + HQHPD VLQFH 2018.10/01-10/08(total 16 times of enema plus IV esmolol). Gastrostomy was performed on 10/08 DQG 378 ZDV VKLIW WR PJ 4 + 32 VLQFH 7K\URLG IXQFWLRQ RQ VKRZHG 76+ uIU/mL, free T4: 2.14 ng/dL and PTU shifted to PTU to 150mg BID PO. Thyroid function on 10/31 showed TSH < 0.005 uIU/mL, free T4: 1.11 ng/dL with relative stable heart rate around 80-100 times/ min.

Discussion: ,Q VRPH VSHFL¿F VLWXDWLRQ VXFK DV 338 VHYHUH *, EOHHGLQJ RU KLJK ULVN RI 1* WXEH insertion, how could anti-thyroid drugs be given become a problem. However, PTU and methimazole enema are effective and safe treatment after review the literature. The detail results of literature review would show on poster.

Conclusion: Propylthiouracil enema is a effective and safe treatment while patient can’t prescribe anti-thyroid drug from oral or NG route.

159

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE22

CONCOMITANT PRESENTATION OF DIABETIC KETOACIDOSIS AND THYROTOXICOSIS IN A PREGNANT WOMAN- A CASE REPORT 1

YING-LEIN CHENG, 1YU-MEI CHIEN, 1.2TING-WEI LEE, 1HAN-WEN LAO, 1 YU-CHUN HSUEH, 1.3TING-I LEE 1

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

Diabetic ketoacidosis (DKA) is an acute complication that may have devastating consequences if not managed promptly and effectively. DKA is mostly seen in type 1 diabetes mellitus (DM) patient.

Although simultaneous presentation of thyrotoxicosis and DKA have been reported, it is a clinically that remains a diagnostic and management challenge in clinical practice. Herein, we described a rare of concurrent presentation of a newly diagnosed DM complicated with DKA and thyrotoxicosis in a pregnant women.

A 40-year-old women with intrauterine pregnancy 33 weeks presented to our Emergency room due to back pain, diarrhea, nausea and vomiting for few hours. Seven days prior to visit, she had common cold and headache with medication from local clinic. Her Gestational history was G4P1SA1AA1 with normal prenatal physical examination. 100g oral glucose load at 28th weeks of gestation exclude diagnosis of gestational DM. She denied past medical history. She had cesarean section five years ago. She denied of any heredofamilial disease. On physical examination, height was 166 cm and body weight 63 kg with body mass index 22.8 kg/m2 (previous BW 52kg). She is afebrile with blood pressure 160/79 mm Hg, heart rate 140 beats/min, respiratory rate 27 breaths/min and 97% O2 saturation at room air. Her skin was dry, with vitiligo. Thyroid gland was diffuse grade 2 JRLWHU 7KHUH ZHUH QR SURSWRVLV QR GRXEOH YLVLRQ QR KDQG WUHPRU QR SHGDO HGHPD QRU K\SHUUHÀH[LD Unfortunately, absent of fetal heart beats was found at the Emergency room, and she underwent emergent cesarean section, and delivered a stillborn baby girl. Laboratory results revealed random blood glucose of 418mg/dL, high anion gap metabolic acidosis (pH of 7.24, HCO37.6 mmol/l, anion gap of 20.4 mmol), and ketone body 5mmol/l. Her renal, liver function, and electrolytes were normal.

The patient was treated as DKA. Additional investigation showed HbA1c 6.3%, fasting C-peptide was 0.4 ng/ml, tyrosine phosphatase antibodies was negative but positive glutamic acid decarboxylase antibodies. Glucagon stimulation test showed blood glucose and C-peptide at 0’ and 6’ were 210 mg/ dl and 234mg/dl, and 0.26 ng/ml and 0.71 ng/ml, respectively. Type 1 DM was highly suspected and +/$ KDSORW\SH DOVR VKRZHG SRVLWLYH IRU '4 '5 0RUHRYHU GXH WR KHU YLWLOLJR DQG GLIIXVH JUDGH 2 goiter, thyroid was further evaluated. Results showed serum FT4 2.43 ng/dl, TSH 0.04 uIU/ml, Her

160

Abstract

anti-thyroglobulin antibodies was negative, but positive for anti-thyroid peroxidase antibodies and TSH receptor antibody. Follow-up of thyroid functions showed T3 449.14ng/dl, FT4 4.33ng/dl, and she was treated as Graves’ disease in thyrotoxic state.

161

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE23

A NEW BIOCHEMICAL SCREENING TEST FOR THE DEFINITIVE DIAGNOSIS OF ENDOGENOUS CUSHING’S SYNDROME: MORNING LOW-DOSE DEXAMETHASONE SUPPRESSION TEST SHIH-CHEN TUNG, PEI-WEN WANG Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

Introduction: Endogenous Cushing’s syndrome (CS) is a rare severe condition resulting from a chronic excessive endogenous glucocorticoid secretion that causes systemic morbidity and a higher mortality risk. The definitive diagnosis of endogenous CS is a challenge in clinical endocrinology. %LRFKHPLFDO FRQ¿UPDWLRQ RI &6 UHOLHV XSRQ WKH PHDVXUHPHQW RI EDVHOLQH K XULQDU\ IUHH FRUWLVRO (UFC), plasma cortisol circadian rhythm assessment, low-dose dexamethasone suppression test (LDDST), and mid-night plasma cortisol or late-night salivary cortisol levels.

Now, we present a new biochemical screening test, e.g. morning low-dose dexamethasone VXSSUHVVLRQ WHVW IRU WKH GH¿QLWLYH GLDJQRVLV RI &6 ZKLFK ZDV QHYHU UHSRUWHG Materials and methods: From June 2001 to January 2017, endogenous CS was diagnosed in 24 subjects who morning LDDST (1 mg dexamethasone administered orally at 07:00 h and plasma cortisol withdrawn at 16:00 h) was performed. Other traditional screening tests for CS were also performed including baseline morning (08:00 h to 09:00 h) and afternoon (16:00 h to 22:00 h) plasma cortisol levels, baseline 24-h UFC, and overnight and 2-day LDDST. /RVV RI SODVPD FRUWLVRO FLUFDGLDQ UK\WKP LV GH¿QHG DV EDVHOLQH DIWHUQRRQ SODVPD FRUWLVRO OHYHO !

7.5 mg/dl and > 50% of baseline morning plasma cortisol level. Non-suppression of morning LDDST is defined as afternoon plasma cortisol level at 16:00 h > 5 mg/dl. Non-suppression of overnight LDDST (administration of 1 mg dexamethasone orally at 23:00 h) is defined as morning 08:00 h plasma cortisol level > 5 mg/dl. Non-suppression of 2-day LDDST (0.5 mg dexamethasone orally HYHU\ KRXUV IRU GD\ LV GH¿QHG DV K 8)& IURP VHFRQG WR WKLUG GD\ ! PJ RU PRUQLQJ h plasma cortisol level at the third day > 5 mg/dl.

Plasma cortisol and UFC were measured by radioimmunoassay (RIA) kits. Plasma ACTH levels were measured by RIA or immunoradiometric assay.

Results: The mean age of these 24 patients at the time of surgery was 43.4 ± 11.9 years old. Sex distribution is 19 females and 5 males, respectively. The distribution of the causes of CS is 17 patients with adrenal CS (12 patients with adrenocortical adenoma, one with adrenocortical carcinoma, two with primary pigmented nodular adrenocortical disease, and two with ACTH-independent bilateral PDFURQRGXODU DGUHQRFRUWLFDO K\SHUSODVLD DQG VHYHQ ZLWK $&7+ GHSHQGHQW &6 ¿YH ZLWK &XVKLQJ¶V disease and two with ectopic ACTH syndrome).

The sensitivity of biochemical screening tests for CS with morning LDDST is 91.7% (22/24), 162

Abstract

overnight LDDST 95.5% (21/22), loss of diurnal rhythm 95.8% (23/24), baseline 24-h UFC 100% (19/19), and plasma cortisol at 08:00 h after 2-day LDDST 91.7% (11/12).

Conclusions: 1. The sensitivity of the screening test for endogenous CS with morning LDDST is 91.7%, not higher or lower rate as compared with other traditional reported screening tests of CS ௅ 2. It is more convenient for patients to go to hospital afternoon for withdrawing blood with morning LDDST.

163

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE24

TYOSINE KINASE INHIBITORS AND MTOR INHIBITORS RELATED ENDOCRINOPATHY: A CASE REPORT 1

JIA-YIN GUO, 1TZU-YUAN WANG, 1RONG-HSHING CHEN, 1CHWEN-TZUEI CHANG, 1 SHENG-PANG HSU, 1CHING-CHU CHEN, 1CHING-CHU CHEN 1

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

Introduction: There was an enhancing improvement for cancer treatment in the past decades.

Among medicines for target therapy, tyrosine kinase inhibitors interfere with molecules essential for tumor growth and mTOR inhibition results in growth suppression. Here, we reported a case using a tyrosine kinase inhibitor and a mTOR inhibitor for treatment of renal cell carcinoma leading to hypothyroidism and diabetes mellitus.

Case report: A 66-year-old male with a history of right renal cell carcinoma (RCC) was first seen at our endocrine out-patient clinic due to referral for management of hypothyroidism. He was diagnosed to have right RCC 9 years ago, received a right radical nephrectomy. Three years ago, the RCC relapsed with lung metastasis. He received palliative radiotherapy and target therapy with Sunitinib, a tyosine kinase inhibitor, for nearly two years, then switching to axitinib, another tyosine kinase inhibitor, due to bone metastasis one year ago. Ten months ago, thyroid function showed free T4 0.45 ng/dL and TSH 93.52 uIU/Ml, respectively. Both ATA and anti-TPO antibody were negative.

Thyroid ultrasonography showed atrophic thyroiditis. Four months ago, he was found to have prostate malignant epithelioid tumor. Axitinib was replaced with everolimus, a mTOR inhibitor, for prostate cancer therapy. Three months later, hyperglycemia was noticed. HbA1c level was 6.8% and 10% in 2 consecutive three- month interval check-up. He was treated with insulin after metformin monotherapy failure.

Discussion: Tyrosine kinase inhibitors block both vascular endothelial and platelet-derived growth factor receptor to inhibit angiogenesis, which may cause hypothyroidism. The possible mechanism of mTOR inhibitors associated diabetes may be secondary to a reduction of the insulin signaling pathway leading to insulin resistance and a reduction of insulin secretion via a direct effect on the pancreatic beta cells.

Conclusion: It is needed to monitor endocrine functions during target therapy with tyrosine kinase inhibitors and mTOR inhibitors.

164

Abstract

PE25

THYROID INFLAMMATION AND INTRA-NODULAR HEMORRHAGE AFTER FINE-NEEDLE ASPIRATION FOR THYROID CYST: A CASE REPORT 1

CHI-LUNG TSENG, 2CHUN-JUI HUANG

1

Division of Gastroenterology, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: 7K\URLG ¿QH QHHGOH DVSLUDWLRQ GUDLQDJH KDV EHHQ FRQVLGHUHG D JHQHUDOO\ VDIH DQG simple procedure for managing thyroid cysts. Post-aspiration complications are rare, and pain and minor hematomas are the most common. Large intra-nodular hemorrhage is infrequently seen, and WK\URLG LQÀDPPDWLRQ SUHVHQWLQJ OLNH VXEDFXWH WK\URLGLWLV KDV QRW EHHQ UHSRUWHG Clinical case: A 58-year-old Taiwanese male presented to the emergency department with fever DQG SDLQIXO VZHOOLQJ RYHU ULJKW QHFN WKUHH GD\V DIWHU ¿QH QHHGOH DVSLUDWLRQ IRU WK\URLG F\VW +H KDG a long history of multi-nodular goiter, diabetes mellitus, hypertension, and hepatitis B carrier. Rapid enlargement of thyroid nodule was noted in September, 2017, with largest one measuring 9.0 cm over right thyroid. Since then, he started to receive fine needle aspiration fluid drainage 21-50 c.c. each time every two to three months for his thyroid cyst. Surgical intervention was suggested but the patient refused. In August, 2018, another 50 c.c. of brownish cystic fluid was drained for a 5.6 cm thyroid cyst. Unfortunately, fever and enlargement of right neck mass developed three days afterwards.

His vital signs were temperature 38.5°C, heart rate 102 beats per minute, respiratory rate 20/min, blood pressure 146/88 mmHg. Physical examination revealed right side stony-hard thyroid with tenderness. Hemogram and thyroid function were normal but markedly elevated C-reactive protein level to 19.3 mg/dL (normal: 0.0-0.5) was found. There was no evidence of infection on urine routine, CXR, abdominal sonography, and blood cultures. Neck computed tomography (CT) scan disclosed multi-nodular goiter with intra-nodular hemorrhages up to 5 cm in right thyroid. Findings on thyroid sonography were compatible. Intravenous antibiotic with Piperacilin/tazobatam was administered for suspicious acute suppurative thyroiditis and later shifted to cefepime plus metronidazole. Fine needle aspiration drainage was performed over right thyroid, and the bacterial culture, tuberculosis smear and culture of the 25 c.c. bloody aspirate were negative. Fever and neck pain persisted despite antibiotics IRU PRUH WKDQ RQH ZHHN )RU VXUYH\ RI IHYHU RI XQNQRZQ RULJLQ DQ LQÀDPPDWLRQ VFDQ ZDV RUGHUHG DQG RQO\ LQFUHDVHG XSWDNH RYHU ULJKW WK\URLG ZDV ORFDWHG LQGLFDWLQJ WK\URLG LQÀDPPDWLRQ 7KHUH ZDV also elevated level of erythrocyte sedimentation rate (ESR) to 83 mm/hr (normal: 0-20). Therefore, we treated him as subacute thyroiditis with prednisolone 20 mg B.I.D. Fever, neck pain and swelling improved and prednisolone dosage was tapered. Twenty days later, ESR normalized to 18 mm/hr.

165

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Clinical lesion: Although fine needle aspiration of the thyroid is a relatively safe procedure, FRPSOLFDWLRQV VXFK DV ODUJH LQWUD QRGXODU KHPRUUKDJH DQG WK\URLG LQÀDPPDWLRQ PD\ RFFXU LQ SDWLHQWV with frequent aspirates of large amounts.

166

Abstract

PE26

A CASE OF ONCOCYTIC ADRENOCORTICAL CARCINOMA WITH FUNCTIONING CLINICAL PRESENTATION 1

SHIH-PEI CHEN, 1YI-HONG ZENG, 1CHUN-CHUAN LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

Oncocytic adrenocortical carcinoma is a rare histopathological variant of adrenocortical carcinoma with very few instances reported in the literature to date. We report a case of oncocytic adrenocortical carcinoma with functioning clinical presentation. 36-year-old female complained of body weight gain 10 kg within 1 month, leg edema, acne over neck and forehead. In addition, insomnia, dizziness, headache, and hypertension (systolic blood pressure 160mmHg at home) were noted. Due to abdominal pain, she went to our outpatient department for help. Lab data showed WBC:6.9 10^3/uL, Hemoglobin:14.5 g/dL, Platlet221 10^3/uL , blood sugar 100mg/dL, GPT 20 IU/L,creatinine 0.8 mg/dL , Na/K 144/3.8mEq/L, Ca 9.3 mg/dL , Aldosterone 5.74ng/dL, Plasma UHQLQ DFWLYLW\ QJ G/ KU UHVSHFWLYHO\ 2YHUQLJKW GH[DPHWKDVRQH WHVW VKRZHG FRUWLVRO ȝJ dL. Computerized tomography scan revealed a 6.7cm heterogeneously right adrenal mass mass with possible thrombus within IVC at the level of right adrenal tumor. Positron Emission Tomography showed a large mass of markedly, heterogeneously increased tracer uptake (SUVmax: 15.3) in right adrenal region with slightly decreased delayed phase radioactivity (SUVmax: 14.1). She underwent operation of excision right retroperitoneal malignant adrenal tumor with partial right nephrectomy and excision part of IVC. Pathology was proven right adrenal cortical carcinoma, oncocytic variant.

Then, she received adjuvant radiotherapy and Mitotan.

167

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE27

A CASE OF PRIMARY HYPERPARATHYROIDISM WITH VITAMIN D DEFICIENCY HUI-I YU, FANG-PING KUNG, TSAI-SUNG TAI Ditmanson Medical Foundation Chia-Yi Christian Hospital

A 65-year-old male, presented with histories of hypertension, renal stone, chronic constipation, insomnia. He had ever admitted due to acute pancreatitis and high calcium level 12 mg/DL and I-PTH being 961 pg/ml was shown. Then he was referred to our hospital. Laboratory investigations revealed Alb: 3.3, Total calcium: 14.4, Ion.Ca:2.03, P:1.0, I-PTH:1149.1, Na:131mmol/L, K:3.31mmol/l, mg: 1.87. Low plasma 25(OH)D3 levels, 25(OH)D3 being 9 ng/ml (normal values <30 ng/ml) was observed. Thyroid ultrasound found cystic goiter and parathyroid adenoma, right 26.3x20.3x18.3mm.

Tc-99m T1-201 Subtraction scan showed parathyroid adenoma in the inferior pole of right thyroid lobe. Bone mineral density study was measured in the neck of the left femur and L-spine DQG UHYHDOHG D 7 VFRUH RI í :H JDYH KLP K\GUDWLRQ ZLWK ORRS GLXUHWLFV DQG DUHGLD WUHDWPHQW IRU K\SHUFDOFHPLD 9LWDPLQ ' VXSSOHPHQWDWLRQ ZDV JLYHQ DIWHU YLWDPLQ ' GH¿FLHQF\ ZDV IRXQG 7KHQ KH received right parathyroidectomy. Post-Operation his calcium and phosphate level returned to normal, Calcium level being 9.2 mg/dl, Phosphate level being 3.8 mg/dl. His I-PTH level dropped to 23.7 pg/ ml. He received temporarily calcium supplement and maintain Vitamin D supplementation without hungry bone syndrome.

Conclusions: 9LWDPLQ ' GH¿FLHQF\ LQVXI¿FLHQF\ VHHPHG WR EH PRUH SUHYDOHQW LQ SDWLHQWV ZLWK primary hyperparathyroidism (PHPT) than in general population. It is often associated with more severe PHPT with higher PTH level or bigger size of adenoma. Cautious vitamin D supplementation before operation does not aggravate hypercalcemia and might reduce the risk of hungry bone syndrome following surgery. Thus, Vitamin D status assessment in patients with PHPT is important.

168

Abstract

PE28

PULMONARY EMBOLISM AS THE INITIAL PRESENTATION OF ADRENAL CUSHING SYNDROME 1

YU-CHIEH CHANG, 1CHUN-CHUAN LEE, 1YI-HONG ZENG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

Background: Cushing syndrome is associated with a hypercoagulable state results in a 10-fold increase in the incidence of venous thromboembolism(VTE) compared with the general population. *OXFRFRUWLFRLG H[FHVV PRGL¿HV FRDJXODWLRQ DQG ¿EULQRO\WLF SDUDPHWHUV SRVVLEO\ E\ XS UHJXODWLRQ RI gene transcription. The hypothesis is supported by the increase in coagulation factors with subsequent shortening of aPTT and normalization after treatment. Pulmonary embolism and deep venous thrombosis are the two most important manifestations of venous thromboembolism (VTE). We hereby report a case with pulmonary embolism as the initial presentation of Cushing syndrome.

Case Report: A 63-year-old female with type 2 diabetes and hypertension presented to our emergent department with chest tightness and shortness of breath. Her vital signs: body temperature 37.3 ɗ , pulse 100/min, respiratory rate18/min, blood pressure: 149/83 mmHg. The patient has the appearance of central obesity with several ecchymosis over her limbs and trunk. Laboratory investigation showed white blood cell count 8700/uL, segment 59%, PT 11 sec, aPTT 25.5 sec, creatinine 0.9 mg/dL, sodium 141 mEq/L , potassium 2.5 mEq/L, GPT 66 IU/L , troponin-I 0.57 ng/ mL, CKMB 6.3 ng/mL, BNP 297 pg/mL and D-dimer 5671 ng/mL. Arterial blood gas showed pH 7.506, pCO2 27 mmHg, pO2 72 mmHg, HCO3 22 mmol/L, B.E. 0.5 mmol/L, SaO2 96%. EKG showed sinus tachycardia. Chest x ray showed cardiomegaly with engorged pulmonary trunk. &RPSXWHG WRPRJUDSK\ DQJLRJUDSK\ &7$ UHYHDOHG SURPLQHQW ¿OOLQJ GHIHFWV LQ OHIW PDLQ VXSHULRU and inferior branches of bilateral pulmonary arteries, indicating pulmonary embolism. Furthermore, a 3cm heterogenous mass of left adrenal gland was noted. Venous ultrasound showed thrombosis over the right popliteal vein causing partial occlusion. The patient was given anticoagulant and was closely monitored in our intensive care unit (ICU). )XUWKHU VXUYH\ RI OHIW DGUHQDO PDVV UHYHDOHG '+($ 6 ȝJ G/ DOGRVWHURQH QJ G/ UHQLQ QJ P/ KU $55 QJ GO SHU QJ PO KRXU VHUXP FRUWLVRO ȝJ G/ KU XULQH FRUWLVRO ȝJ GD\ XULQDU\ FDWHFKRODPLQHV WHVW QRUHSLQHSKULQH XJ GD\ HSLQHSKULQH XJ GD\ GRSDPLQH 88.3 ug/day, urinary vanillylmandelic acid(VMA) test 5.8 mg/day. Cortisol of overnight dexamethasone suppression test, low-dose dexamethaone suppression test, high-dose dexamethasone suppression WHVW ZHUH ȝJ G/ ȝJ G/ DQG ȝJ G/ UHVSHFWLYHO\ 7KH GLDJQRVLV RI DGUHQDO &XVKLQJ syndrome was confirmed and she received laparoscopic left adrenalectomy with pathology reported FRUWLFDO DGHQRPD $IWHU WKH RSHUDWLRQ VKH WRRN &RUWLVRQH DFHWDWH WR SUHYHQW DGUHQDO LQVXI¿FLHQF\ 169

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Conclusion: The etiology of Cushing syndrome includes corticotrope adenomas in the pituitary (Cushing’s disease), ectopic corticotropin (ACTH) production by tumors (eg, small cell carcinoma), or adrenal adenomas and carcinoma. Pulmonary embolism is a peculiar initial presentation of Cushing syndrome. It is suggested that Cushing syndrome should be considered in a patient with hallmark manifestations and pulmonary embolism.

170

Abstract

PE29

MANAGEMENT OF COMPLICATED THYROTOXICOSIS WITH EXTRACORPOREAL MEMBRANE OXYGENATION 1

SZU-HAN LIN, 1SHANG-REN HSU, 1YU-FANG CHENG, 1PO-CHUNG CHENG, 1 DONG-HWA TSAI 1

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

Uncontrolled thyrotoxicosis may have catastrophic consequences. During the year 2018, three hyperthyroid patients were admitted to our hospital for serious complications that required life support with extracorporeal membrane oxygenation (ECMO).

Case 1 is a 35-year-old man who had bilateral proximal lower limb weakness in the morning and was discovered to have hypokalemia. While at the emergency department, refractory ventricular tachycardia developed, leading to cardiac arrest and initiation of ECMO. The patient was found to be K\SHUWK\URLG WKHUHE\ FRQ¿UPLQJ WKH GLDJQRVLV RI WK\URWR[LF SHULRGLF SDUDO\VLV &RXUVH ZDV IXUWKHU complicated with rebound hyperkalemia following potassium replenishment. After appropriate treatment, the patient stabilized and was freed from ECMO. Case 2 is a 55-year-old woman with Graves’ disease managed with subtotal thyroidectomy more than 20 years ago. She presented with worsening exertional dyspnea, leg edema, and palpitations of RQH ZHHN¶V GXUDWLRQ $WULDO ¿EULOODWLRQ ZLWK UDSLG YHQWULFXODU UDWH ZDV LQLWLDOO\ IRXQG 6KH ZDV DGPLWWHG for cardiorespiratory failure which required endotracheal intubation. After admission she had cardiac arrest due to ventricular tachycardia and was supported with ECMO. Hyperthyroidism was diagnosed as well as severe mitral regurgitation and poor ventricular function. After anti-thyroid drug treatment and heart valve replacement surgery, the patient improved and was discharged in stable condition.

Case 3 is a 28-year-old man with irregularly treated Graves’ disease who presented with chest tightness since the day before. Goiter and elevated thyroid hormones were found. Initial electrocardiogram revealed intermittent short run ventricular tachycardia. Coronary angiography was performed, which showed left anterior descending artery myocardial bridging. The patient was discharged following treatment with anti-thyroid drug and Lugol’s solution. However, he was readmitted 6 days later for thyrotoxic crisis and refractory ventricular tachycardia requiring initiation of ECMO. Escape from the inhibitory effect of iodine load on thyroid function was considered a plausible cause. After appropriate anti-thyroid treatment, the patient was successfully freed from ECMO. These cases demonstrate the usefulness of ECMO as a lifesaving measure for patients with FRPSOLFDWHG WK\URWR[LFRVLV SULRU WR GH¿QLWH GLDJQRVLV DQG PDQDJHPHQW RI WKHLU K\SHUWK\URLGLVP DQG other aggravating conditions.

171

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE30

LITHIUM-INDUCED HYPERTHYROIDISM: A CASE REPORT 1

CHIN-CHOU YANG, 2PENG-NIEN WANG

1

Division of General Medicine, Department of General Psychiatry, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 2Department of General Psychiatry, Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan

Background: Lithium is widely used as a mood stabilizer in managing mental illness, mainly mania and bipolar disorder. In this article, we report a 38 years old woman admitted for schizophrenia.

Lithium-induced hyperthyroidism was found during admission.

Methods: A 38 years old woman without systemic disease was admitted to our psychiatric ward under the diagnosis of schizophrenia. The routine laboratory study revealed normal thyroid IXQFWLRQ DW ¿UVW 7 XJ GO 7 QJ GO +HU PHGLFDWLRQ LQFOXGHG 2ODQ]DSLQH )OXQLWUD]HSDP , Clonazepam, Biperiden, and Lithium. These medications remained the same in recent one year.

In August 2018, abnormal thyroid function was found. (TSH < 0 uIU/ml, FT4 2.35 ng/dl). Thyroid antibodies were within normal range (TSHR-Ab negative, anti-TPO Ab: 31 IU/mL). The patient denied any discomfort. So we kept closely observation and followed thyroid function 1 month later.

The data revealed: TSH < 0 uIU/ml, FT4 2.59 ng/dl. The tentative diagnosis was Lithium-induced hyperthyroidism. Methimazole was prescribed for hyperthyroidism treatment.

Results: The thyroid axis is prone to interactions with many drugs, and hypothyroidism is the most common condition of drug-induced thyroid dysfunction (1). Lithium is wildly used as treatment for schizophrenia and is often associated with a decline in renal function, hypothyroidism, and hypercalcemia (2). Thyroid disorders such as goiters and hypothyroidism are common complications of the use of lithium. Although the occurrence of lithium-induced hyperthyroidism is rare, it has still been reported (3). The mechanism of lithium-induced hyperthyroidism is not well understood.

However, this condition can generally be controlled medically and there is no need to discontinue /LWKLXP WUHDWPHQW HVSHFLDOO\ ZLWKRXW FRQVXOWDWLRQ ZLWK WKH SDWLHQW¶V SV\FKLDWULVW ¿UVW Conclusions: We report a case of lithium-associated hyperthyroidism. The condition was resolved by Methimazole. It is strongly recommended to evaluate thyroid function before starting to treat psychic patients with Lithium. If hyperthyroidism develops, treatment should be carried out according to guidelines, and it does not always require withdrawal of lithium.

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

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

2.SHINE, Brian, et al. Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data. The Lancet, 2015, 386.9992: 461-468.

172

Abstract

3.CHALASANI, Santhi; BENSON, Katherine A. Lithium-induced thyrotoxicosis in a patient with treatment-resistant bipolar type I affective disorder. Med J Aust, 2014, 201.9: 541-542.

173

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE31

PAPILLARY THYROID CARCINOMA COMBINED WITH SKIN DISTANT METASTASIS 1

CHING-LING TU, 1HSING-YI HUANG, 1HE-JIUN JIANG, 1WEI-WEN HUNG, 1 PI-JUNG HSIAO, 1SHYI-JANG SHIN, 1MEI-YUEH LEE 1

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

Papillary thyroid carcinoma has three types of tumor recurrences including postoperative nodal metastases, local recurrence, and postoperative distant metastases. Papillary thyroid carcinoma usually has outside regional lymph nodes metastasis and lung distant metastasis. Fewer than 1% of all patients with papillary carcinoma, had cutaneous metastases. We report a case of papillary thyroid carcinoma with lymph-vascular invasion and minimal extrathyroid extension, post total thyroidectomy and I-131 therapy initially. However, post-operation thyroglobulin level kept elevating. Thyroid echo found residual thyroid tissue and neck CT found residual thyroid tissue and multiple nodules in the right anterior lower neck. Radical thyroidectomy with unilateral lymph node dissection, and skin and VXEFXWDQHRXV WXPRU H[FLVLRQ ZHUH DOVR SHUIRUPHG 7KH SDWKRORJ\ UHSRUW FRQ¿UPHG SDSLOODU\ WK\URLG carcinoma with lymph nodes and skin and subcutaneous metastasis.

Case presentation: This 42 years old female patient didn’t have any systemic disease, who presented with palpable anterior neck mass near right supraclavicular area for 2 months with symptoms including foreign body sensation and mild compression feeling while swallowing in 2014.The mass did not induce pain.She denied dysphagia, odynophagia, hoarseness, dyspnea, fever, sore throat, cough, or other common cold symptoms. She also denied palpitation, easily sweating, hands tremors, and body weight loss. She never smoked, and denied alcohol and betel nuts use. About her family history, her cousin had unknown thyroid disease.

Lab data showed normal thyroid function (TSH: 4.87uIU/ml(0.25-4) , Free T4: 1.03ng/dl(0.71.8)) but elevated thyroglobulin level (Thyroglobulin: 54.61ng/ml(< 50)). thyroid echo found right single hypo-echoic nodular goiter (1.86cm*1.07cm). Thyroid fine needle aspiration (FNA) was done and FNA cytology report was nondiagnostic result ((Bethesda System for Reporting Thyroid Cytopathology; diagnostic category I).)

We recommended rearrange thyroid FNA and recommended patient to avoid Iodine-rich foods. But the patient lost follow-up. She finally came back 2 years later due to referral from our GS(general surgeon) department. The patinet’s thyroid nodule enlarged to more than 4cm, so the VXUJHRQ SHUIRUPHG WRWDO WK\URLGHFWRP\ DQG QHFN GLVVHFWLRQ 7KH SDWKRORJ\ UHSRUW FRQ¿UPHG SDSLOODU\ thyroid carcinoma (PTC): a 4.5cm malignant nodule at right lobe with lymph-vascular invasion and minimal extrathyroid extension (to perithyroid soft tissue or skeletal muscle). There was negative for 174

Abstract

malignancy in a small regional lymph node in section but the surgical margin was involved. AJCC 8th staging was T3bN0AmX, stageI, ATA High Risk.

We then arranged post-operation neck sonography but no obvious remnant found. We also prescribed thyroxine for hormone supplement and therapy. Post-operation thyroglobulin (Tg) persistently maintained more than 10ng/ml(13.3ng/ml), and we arranged high-dose radioactive iodine (RAI). Subsequent whole body scan (WBS) revealed residually biological remnants in the right tubercle and pyramid, a faint radioiodine avid lymph nodes in the left supraclavicle basin (N1b), and less image evidence of I-131 avid distant metastasis.

After completed I131 therapy, out-patient-department follow-up Tg was still elevating from 13.3ng/ml to 84.8ng/ml within 6 months. Therefore, we re-arranged neck sonography that found thyroid tissue remnants this time. Neck CT with contrast revealed bilateral residual thyroid glands, multiple nodules in right anterior lower neck and borderline enlarged right neck level IV lymph nodes. Radical thyroidectomy with unilateral lymph node dissection was smoothly done; skin and VXEFXWDQHRXV WXPRU H[FLVLRQ ZHUH DOVR SHUIRUPHG 7KH SDWKRORJ\ UHSRUW FRQ¿UPHG 37& ZLWK O\PSK nodes and skin metastasis. The patient then accepted further I131 therapy again.

Discussion: Papillary thyroid carcinoma has three types of tumor recurrences including postoperative nodal metastases, local recurrence, and postoperative distant metastases. Papillary thyroid carcinoma usually has outside regional lymph nodes metastasis and lung distant metastasis.

Fewer than 1% of all patients with papillary carcinoma, had cutaneous metastases in thyroid cancer case, palpation of the thyroid bed and lymph node areas is routinely performed. Ultrasonography is more sensitive and may detect lymph nodes as small as 2 to 3 mm in diameter. Thyroglobulin (Tg) is a glycoprotein that is produced only by normal or neoplastic thyroid follicular cells. Serum Tg should not be detectable in patients who have had total thyroid ablation. Here, we presented a case ZLWK SDSLOODU\ WK\URLG FDUFLQRPD ZLWK VNLQ GLVWDQW PHWDVWDVLV WKDW ZDV FRQ¿UPHG E\ SDWKRORJ\ UHSRUW Physical examination, thyroid echo, serum thyroglobulin for follow-up are needed.

175

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE32

78 YEARS OLD WOMAN WITH EXTREME HYPOTHYROIDISM PRESENTING WITH MYXEDEMA COMA 1

LIU FEN, 1WANG HUI

1

Cardinal Tien Hospital

Background: This 78 years old woman was brought to our emergency department for decreased mental status with scanty urine output for 1 day.Abnormal thyroid thyroid function hypothyroidism was noted,after thyroid hormone replacement,her consciousness become improved.

Conclusions: Myxedema coma is a true endocrine emergency requiring early and appropriate treatment. Patients presenting to the emergency department with hypothermia are rare and often require prompt diagnosis and management.

176

Abstract

PE33

ECTOPIC PAPILLARY CARCINOMA FOUND IN GRAVES’ DISEASE: A CASE REPORT 1

JIA-YIN GUO, 1CHWEN-TZUEI CHANG, 1MAO-TSU FUH, 1RONG-HSHING CHEN, 1 TZU-YUAN WANG, 1WEI-LUN HUANG, 1CHING-CHUNG CHAN, 1YIN-HUEI CHEN, 1 SHENG-PANG HSU, 1CHING-CHU CHEN 1

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

Introduction: Papillary thyroid carcinoma was the most common type of thyroid cancer, with a favorable prognosis. Here, we report a rare case of papillary thyroid carcinoma arising from ectopic thyroid gland in Graves’ disease.

Case report: $ \HDU ROG SUHYLRXVO\ KHDOWK\ IHPDOH ZDV ¿UVW VHHQ DW RXU HQGRFULQH RXW SDWLHQW clinic due to hyperthyroidism with initial presentation of palpitation. Physical examination showed diffuse thyroid goiter grade II, with one elastic nodules about 2 cm on right side. Thyroid function showed free T4 3.45 ng/dL and TSH 0.018 uIU/Ml. TSH Receptor antibody was 51.9%. Thyroid ultrasonography revealed one 6.1*9.3 mm hypoechoic nodules in left side. One hypoechoic nodule 10.6*12.5 mm with calcification and irregular margin was noticed in right side. Also, another two isoechoic lesions with 15.2*12.3 mm and 16.4*34.4 mm located lateral to right thyroid area and was near to internal carotid artery was noted, suspect of ectopic thyroid tissue. Fine needle aspiration showed negative of malignancy. Due to Graves’s disease with suspect ectopic thyroid gland, operation with right thyroid lobectomy, left subtotal thyroidectomy and right neck dissection to remove ectopic thyroid gland was done three months later. Unexpectedly, Pathology showed papillary thyroid carcinoma of follicular variant of right lobe, multifocal papillary microcarcinoma, arising from ectopic thyroid, p T3 according to AJCC 7th edition . Left lobectomy for complete tumor excision was done.

Two weeks later, which pathology showed papillary thyroid carcinoma with follicular variant, no lymph node metastasis found. Post-operation radioiodine I-131 with 150 mci was administered. There was no recurrence noted during follow up.

Discussion: Ectopic thyroid gland may be found along the line of the obliterated thyroglossal duct, usually from the tongue to the diaphragm, which may have associated with either hypofunction or hyperfunction. Rarely, malignant neoplastic changes can occur in ectopic thyroid tissue. Surgery is a prudent choice due to the potential of malignant evolution of ectopic thyroid tissue.

Conclusion: For ectopic thyroid tissue, in addition to evaluate of hormone-producing function, elaborate ultrasonography examination for nodular disease or malignant transformation was also VLJQL¿FDQW

177

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE34

A CASE OF HUGE PAPILLARY THYROID CARCINOMA IN STRUMA OVARII BUT NEGATIVE FINDINGS IN THYROID GLAND AND REVIEW OF LITERATURE MIN-TSUN CHIU, KAI-JEN TIEN, MEI-CHEN YEH, NAI-CHENG YEH, SHANG-GYU LEE, CHEWN-YI YANG Division of Endocrinology and Metabolism, Department of Internal medicine, Chi Mei Medical Center, Tainan, Taiwan.

Objective: Thyroid tissue is not commonly seen in ovary. Struma ovarii is diagnosed when thyroid tissue is the predominant element (> 50%) in ovarian teratoma. About 5% of all ovarian teratomas are struma ovarii. Due to the rarity of the disease, there is no consensus on the optimal treatment of women with malignant struma ovarii. Here we present a rare case of huge struma ovarii with papillary thyroid carcinoma, and we review the management and treatment option of this rare tumor.

Methods: In this article, one case of struma ovarii was reviewd. A 47-year-old female was presented to out-patient department of gynecology due to vaginal spotting. Menopausal was found for 6 years then. Before menopausal, there was dysmenorrhea and hypermenorrhea during menstral period. Transvaginal ultrasonography was arranged and showed diffused heterogeneously echogenic mass with 8.6 cm in size found in posterior uterine wall. Lab data showed elevation of tumor markers (CA125, CA199).

Results: Total abdominal hysterectomy with bilateral salpingo- oophorectomy (TAH/BSO) was done. Pathology showed papillary thyroid carcinoma. Tumor markers fell back after surgical intervention. Thyroid echo followed at out-patient department of endocrine showed no positive of tumor or malignancy. Antithyroglobulin antibody, anti-thyroid peroxidase, T4, TSH, and thyroglobulin were within normal limit.

Conclusions: The choice of optimal treatment is still uncertain. However, for malignant struma ovarii, local resection of ovarian lesion and thyroid evaluation should be done. The need for VXEVHTXHQW WRWDO WK\URLGHFWRP\ ZDV FRQWURYHUVLDO LI QHJDWLYH ¿QGLQJV LQ WK\URLG JODQG

178

Abstract

PE35

DE MORSIER’S SYNDROME WITH DIABETES INSIPIDUS, A CASE REPORT 1

CHUN FENG WU, 1PIN FAN CHEN, 1BING RU GAO, 1WEI CHENG LIAN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Background: de Morsier’s Syndrome, also called Septo-optic dysplasia (SOD) is a rare congenital abnormality and characterized by a classic triad of optic nerve hypoplasia, midline brain GHIHFWV DQG SLWXLWDU\ KRUPRQHV GH¿FLHQF\ 7KH SULPDU\ PDQLIHVWDWLRQ RI K\SRSLWXLWDULVP LV JURZWK UHWDUGDWLRQ LQ FKLOGKRRG VHFRQGDU\ WR JURZWK KRUPRQH GH¿FLHQF\ +HUH LQ ZH UHSRUWHG D 62' FDVH RI complicated hypopituitarism with both anterior and posterior pituitary function defects.

Case presentation: A 29-year-old visually impaired female was referred to our outpatient department for morbid obesity evaluation. Her past medical history included optic nerve dystrophy and growth retardation, which received one-year growth hormone replacement during her early adolescence. The increase in thirst (> 10 liters of water per day) and a large amount of urine amount were also noted for years. Pituitary function showed IGF-1 at very low levels, but normal prolactin, TSH, ACTH and FSH values.

At admission, we arranged the glucagon test and the water deprivation test. The diagnosis of growth hormone deficiency and central diabetes insipidus was confirmed. Brain MRI revealed 1) right optic nerve and chiasm hypoplasia, 2) thin pituitary stalk and an intermediate signal of posterior pituitary on T1, and 3) absence of septum pellucidum. We diagnosed SOD according to the MRI finding, pituitary dysfunction, and optic nerve defect. The polyuria improves after desmopressin therapy.

Conclusion: SOD was a heterogeneous disorder with multiple system involvement. According WR SUHYLRXV VWXGLHV WKH PRVW FRPPRQ SLWXLWDU\ GH¿FLHQF\ ZDV JURZWK KRUPRQH IROORZHG E\ WK\URLG stimulating hormone, adrenocorticotropin, and gonadotropin. Deficiency of antidiuretic hormone was relatively rare in SOD. For young patients with a history of optic nerve dysfunction and growth KRUPRQH GH¿FLHQF\ 62' ZDV FRQVLGHUHG RQH RI WKH UHOHYDQW GLIIHUHQWLDO GLDJQRVHV (DUO\ GLDJQRVHG ZLWK 62' PD\ DYRLG VHYHUH FRPSOLFDWLRQV IURP SLWXLWDU\ KRUPRQH GH¿FLHQF\ DQG LPSURYH TXDOLW\ of life.

179

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

BP-1

RELATIVE CONTRIBUTION OF BASAL AND POST-PRANDIAL HYPERLGYCEMIA STRATIFIED BY A1C CATEGORIES BEFORE AND AFTER TREATMENT INTENSIFICATION WITH DULAGLUTIDE 1

GUILLERMO UMPIERREZ, 2KEVIN M. PANTALONE, 3CHARLES ATISSO, 3 LAURA FERNÁNDEZ LANDÓ, 3HIREN PATEL, 3THOMAS LEW (NON-AUTHOR PRESENTER) 1

Department of Medicine, Emory University, Atlanta, GA, USA; 2Cleveland Clinic, Cleveland, OH, USA; 3Lilly USA, Indianapolis, IN, USA

Dulaglutide (DU) has demonstrated non-inferiority vs. liraglutide (LIR) and superiority vs. exenatide BID (EXE) in A1c reduction. No data are available on how GLP-1RAs affect the relative contribution of basal hyperglycemia (BHG) and post-prandial hyperglycemia (PPHG) to overall hyperglycemia (OHG) across A1c categories.

Data from five phase 3 studies (N = 673) were pooled to assess the change in relative contributions of BHG and PPHG to diurnal OHG across different A1c categories after 6 months of WUHDWPHQW LQWHQVL¿FDWLRQ ZLWK '8 PJ DV PRQRWKHUDS\ RU ZLWK RUDO PHGLFDWLRQ V LQ W\SH GLDEHWHV patients . BHG and PPHG were calculated using the area under the curve of the 7-point SMPG SUR¿OHV 2YHUDOO FKDQJH LQ %+* IRU '8 YV /,5 DQG '8 YV (;( ZDV DVVHVVHG E\ LQGLYLGXDO VWXGLHV At baseline, relative contributions of BHG increased and PPHG decreased with increasing A1c levels which was maintained after 6 months of treatment with DU despite 1.3% overall mean A1c reduction. At 6 months, the relative contribution of BHG and PPHG were similar between LIR and DU. Relative contribution of BHG was 66.7% (DU) and 66.0% (LIR) at baseline and 55.2% (DU) and 55.9% (LIR) at 6 months. Relative contribution of PPHG was 33.3% (DU) and 34% (LIR) at baseline and 44.8% (DU) and 44.1% (LIR) at 6 months. However, DU had lower BHG but higher PPHG contribution than EXE. Relative contribution of BHG was 63.3 (DU) and 63.1 (EXE) at baseline and 44.7% (DU) and 56.5% (EXE) at 6 months (p <0.001). Relative contribution of PPHG was 36.7% (DU) and 36.9% (EXE) at baseline and 55.3% (DU) and at 43.5% (EXE) at 6 months.

The trend of relative contribution of PPHG and BHG across A1c categories is similar before and DIWHU '8 WUHDWPHQW LQWHQVL¿FDWLRQ LPSO\LQJ LWV HIIHFW RQ ERWK %+* DQG 33+* WR ORZHU $ F

180

Abstract

BP-2

EVALUATION OF CHARACTERISTICS OF DULAGLUTIDE-INDUCED GASTROINTESTINAL ADVERSE EVENTSIN CHINESE PATIENTS WITH TYPE 2 DIABETES MELLITUS 1

ZHIGUANG ZHOU, 2LIYING DU; 2JIANING HOU, 3THOMAS LEW (NON-AUTHOR PRESENTER) 1

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China; 2Lilly Suzhou Pharmaceutical Company, Ltd., Shanghai, China; 3Lilly USA, Indianapolis, IN, USA

Objective: A post hoc analysis to investigate the characteristics of gastrointestinal adverse events (GI AE) in Chinese type 2 diabetes mellitus (T2DM) patients treated with once-weekly dulaglutide in two phase 3 clinical studies.

Methods: In two IMCT phase 3 clinical studies (a glimepiride-controlled monotherapy study NCT01644500 and an insulin glargine-controlled combination therapy study with oral antihyperglycemic drugs NCT01648582), dulaglutide was administered to patients with T2DM at a dose of 1.5 mg or 0.75 mg once weekly. The characteristics (incidence, severity, onset, duration and etc.) of GI AE reported through 26 weeks in Chinese subpopulation in these two studies were investigated.

Results: A total of 787 Chinese patients comprised of the safety analysis subpopulation who had received at least one dose of 1.5 mg or 0.75 mg dulaglutide in the two studies. The most commonly reported GI AEs are diarrhea, nausea, abdominal distension and vomiting, with incidence of 13.1% (103 pt), 6.6% (52 pt), 6.4% (50 pt) and 3.0% (24 pt), respectively. Among patients who experienced diarrhea, nausea, abdominal distension and vomiting during treatment, most of them had mild to moderate symptoms with proportions of 92% (95/103 pt), 88% (46/52 pt), 94% (47/50 pt) and 83% (20/24 pt), respectively. A total of 1.5% (12/787 pt) patients in dulaglutide groups discontinued the WUHDWPHQW GXH WR *, $( 7KH LQFLGHQFH RI *, $(V ZHUH REVHUYHG WR SHDN GXULQJ WKH ¿UVW ZHHNV RI dulaglutide treatment and then declined rapidly, and stayed low until week 26. The median durations of diarrhea, nausea, abdominal distension and vomiting in patients treated with dulaglutide were 4.0 days, 5.0 days, 12.5 days, 4.0 days, respectively.

Conclusions: The most commonly reported dulaglutide-induced GI AE were diarrhea, nausea, abdominal distension and vomiting in Chinese population. They are mostly mild to moderate in severity, and very few patients discontinued treatment. The median duration of dulaglutide-induced GLDUUKHD QDXVHD DQG YRPLWLQJ ZDV UHODWLYHO\ VKRUW GD\V

181

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

BP-3

STATIN TREATMENT ADHERENCE AND ITS PREDICTING FACTORS IN TAIWAN DIABETES PATIENTS 1

LIN TC, 2SHAU WY, 1YANG KAO YH

National Cheng Kung University, Tainan, Taiwan; 23¿]HU ,QF 1HZ 7DLSHL 7DLZDQ

1

OBJECTIVES: To investigate the level, trend and predictors of statin treatment adherence in Taiwan incident diabetes patients. METHODS: :H LGHQWL¿HG D FRKRUW RI LQFLGHQW GLDEHWHV SDWLHQWV aged above 40 years from the Taiwan Longitudinal Cohort of Diabetes Patients database between year DQG 3DWLHQWV ZHUH IROORZHG IURP WKH ¿UVW GD\ UHFHLYHG VWDWLQ DIWHU GLDEHWHV GLDJQRVLV WR WKH end of database in 2012. Statin treatment adherence was measured every 3-month using medication SRVVHVVLRQ UDWLR 035 DQG ZHUH FODVVL¿HG LQWR DGKHUHQW 035 QRQ DGKHUHQW 035

and treatment-stop (MPR = 0%). Multinomial logistic regression with repeated measures was used to explore both baseline and time-varying predictors on non-adherence and treatment-stop. RESULTS: There were 273,461 statin initiators after diabetes diagnoses, and 63% of them were adherent in the ¿UVW PRQWK $GKHUHQFH GHFUHDVHG WR DW WKH HQG RI ¿UVW \HDU DQG UHPDLQHG DW WKLV OHYHO WR ODVW study follow at 11 years. On the other hand, 50% of patients stopped statin treatment after one year, and increased to 56% at end of second year than remained to last study follow up. In multinomial logistic regression analysis, we found baseline covariates, including age, gender, comorbid diseases were associated with adherence or stop significantly, however the strength of associations were at marginal 10% increase or decrease of risk. Indicated by adjusted odds ratio (aOR), time-varying covariates were associated stronger with non-adherence and stop: aOR for more frequent lipid level tests were 0.81 and 0.47; for prescribed in Medical center compared to General Clinics were 0.57 and 0.43, respectively. CONCLUSIONS: The long-term statin adherence was suboptimal in diabetes patients in Taiwan. Analysis of time-varying factors implicates the importance of close watching on patients’ treatment adherence. The results of our study could be applied for developing strategy to improve treatment adherence in diabetes patients needs long-term follow up.

182

Abstract

BP-4

THE IMPACTS OF STATIN ADHERENCE ON ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) IN TAIWAN DIABETES PATIENTS 1

LIN TC, 2SHAU WY, 1YANG KAO YH

National Cheng Kung University, Tainan, Taiwan; 23¿]HU ,QF 1HZ 7DLSHL 7DLZDQ

1

OBJECTIVES: To investigate the risk of ASCVD associated with non-adherent or stopped statin treatments among Taiwan diabetes patients. METHODS: :H LGHQWL¿HG D UHWURVSHFWLYH FRKRUW of incident diabetes patients aged above 40 years, who received statin treatments from Taiwan 1DWLRQDO +HDOWK ,QVXUDQFH FODLPV LQ \HDU WR 3DWLHQWV ZHUH IROORZHG IURP WKHLU ¿UVW VWDWLQ prescription after diabetes diagnosis (the index date) to ASCVD, death, or the end of the study (2013/12/31). Time-varying adherence and covariates were assessed every 3-month. Adherence was PHDVXUHG XVLQJ 0HGLFDWLRQ 3RVVHVVLRQ 5DWLR 035 DQG FODVVL¿HG LQWR DGKHUHQW 035 QRQ adherent (MPR < 80%) and stop in each period. Marginal structure models with stabilized weights were used to adjust for baseline and time-varying confounders to assess the associations between risk of outcomes and non-adherence/stop. RESULTS: There were 273,461 statin initiators after diabetes diagnosis, percentage of adherent decreased from 63% to 30%, non-adherence changing between 40% to 15%, and stop treatment increased to 56% during the follow up. Adherent patients were more likely to receive lipid level tests, treated at higher tiers of medical facilities, and lived in higher urbanization cities during the follow-up. After stabilizing both baseline and time-varying confounders, the Hazard ratio, HR (95%CI) of ASCVD increased when patient non-adherent, 2.27 (2.15-2.38) or stop treatment, 2.41 (2.29-2.55). We also found traditional methods included only baseline confounders may underestimate the association with HR for non-adherent 1.84 (1.78-1.91); for stop 1.27 (1.231.30). CONCLUSIONS: After adjusting for both baseline and time-varying confounders, we found diabetes patients non-adherent or stop their statin treatments may increase their risk for ASCVD more than two-folds, as compared with adherent patients.

183

40

The

th Annual Meeting of March 30-31, 2019 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

BP-5

BASELINE CHARACTERISTICS IN TAIWAN IN THE VERIFY STUDY — A RANDOMISED TRIAL ASSESSING THE DURABILITY OF GLYCAEMIC CONTROL WITH EARLY VILDAGLIPTIN-METFORMIN COMBINATION IN NEWLY DIAGNOSED TYPE 2 DIABETES 1

WAYNE H.-H. SHEU, 2,3,4D.R. MATTHEWS, 5P.M. PALDÁNIUS, 5P. PROOT, 6J.E. FOLEY, 7 M. STUMVOLL, 8S.D. PRATO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital Oxford Centre for Diabetes Endocrinology and Metabolism, 3National Institute for Health Research (NIHR), Oxford Biomedical Research Centre, 4Harris Manchester College, Oxford, UK, 5Novartis Pharma AG, Basel, Switzerland, 6*Novartis Pharmaceutical Cooperation, East Hanover, NJ, USA, 7Divisions of Endocrinology and Diabetes, University Hospital Leipzig, Germany, 8Department of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Pisa, Italy *employee at the time of manuscript preparation.

2

Background / aim: Durable glycaemic control can delay diabetic complications and lead to improved quality of life in people with type 2 diabetes mellitus (T2DM). The ongoing VERIFY trial is WKH ¿UVW VWXG\ WKDW DLPHG WR GHWHUPLQH WKH GXUDELOLW\ RI JO\FDHPLF FRQWURO ZLWK DQ HDUO\ FRPELQDWLRQ RI vildagliptin and metformin versus metformin monotherapy in drug-naïve people with T2DM. Here we report the baseline characteristics of the subjects enrolled in the ongoing VERIFY study in Taiwan.

Methods: We randomised 21 participants among the global (n = 2001) multi-ethnic population, aged 18–70 years, having glycated haemoglobin (HbA1c) levels 48–58 mmol/mol (6.5–7.5%) and body mass index (BMI) 22–40 kg/m2. Baseline data included HbA1c, fasting plasma glucose (FPG) DQG KRPHRVWDVLV PRGHO ȕ FHOO DQG LQVXOLQ DVVHVVPHQWV IRU DOO JOREDOO\ 6WDQGDUGLVHG PHDO WHVWV LQVXOLQ secretion rate relative to glucose (ISR/G), and oral glucose insulin sensitivity (OGIS) were assessed on the global level only.

Results: Out of 21 screened, data were collected from the 21 eligible participants (43% women).

2XU ORFDOO\ DVVHVVHG SDWLHQWV ZHUH SUHGRPLQDQWO\ RI &KLQHVH 7KH PHGLDQ LQWHUTXDUWLOH UDQJH ,45

disease duration was 6.3 months; mean ( ± SD) age 52.8 ± 7.15 years; weight 71.9 kg, and BMI 26.4.

23.8 % of participants were smokers. Baseline HbA1c was 6.9 % and FPG was 7.8 mmol/L. The JOREDO +20$ ȕ DQG VHQVLWLYLW\ YDOXHV ZHUH DQG UHVSHFWLYHO\ ,Q those undertaking meal-tests, the global mean ISR/G was 2 ± 12 pmol/min/m2/mmol/L and OGIS 353 ± 57mL/min/m2.

Conclusions: 2XU FXUUHQW JOREDOO\ PXOWL HWKQLF QHZO\ GLDJQRVHG 9(5,)< SRSXODWLRQ UHÀHFWV also the characteristic presence of early insulin resistance in subjects with increased demand for insulin associated with obesity in our country. The VERIFY study will provide unique evidence in characterising therapeutic intervention in a diverse population with hyperglycaemia, focusing on durability of early glycaemic control.

184