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Invitation "Treatment of Prediabetes and Metabolic Syndrome" 3

2007 Korean Diabetes Association 4

Time Table 17:10~17:30 17:30~19:00 19:00-07:00~08:00 08:00- Room 15:00~17:00 17:00~19:00 19:00-07:00~08:00 08:00-08:00~09:30 09:30~09:50 10:00~11:00 09:50~10:00 Room A I Convention Hall, 4F Welcome Reception Plenary Lecture I Gerald I. Shulman (Yale Univ., USA) Room AII Room B Convention Hall, 4F Convention Hall, 4F Opening Address () Coffee Break Satellite Symposium I, II Breakfast Symposium I Special Symposium Innovative Technology for Diabetes Management Room C Grand Ballroom, 2F Hotel 11:10~12:40 Main Symposium I () New Drug Target I Oral-Presentation I 12:40~13:00 13:00~14:00 Luncheon Lecture I Luncheon Lecture II 14:00~15:00 Plenary Lecture II Body E. Metzger (Northwestern Univ., USA) 15:10~17:10 Highlight Oral Session I () Highlight Oral Session II () Main Symposium II Non-Pharmacological Treatment Coffee Break Breakfast Symposium II 08:00~09:00 Oral-Presentation II Sponsored Special Lecture 09:10~11:10 Main Symposium III Pharmacological Treatment I Oral-Presentation III 11:10~11:30 Coffee Break 11:30~11:50 11:50~12:10 12:10~13:10 Luncheon Lecture III Luncheon Lecture IV 13:10~14:10 Plenary Lecture III George L. King (Harvard Univ., USA) Closing 14:20~16:20 Main Symposium IV Pharmacological Treatment II Main Symposium V New Drug Target II 5

Floor Plan Convention Center 3F Emerald Hall Diamond Hall CONNECTION BRIDGE POSTER EXHIBITION Poster Oral Presentation 1 LOBBY Poster Oral Presentation 2 Information Board Pre & On-site Registration Poster Oral Presentation 5 Poster Oral Presentation 4 Poster Oral Presentation 3 Poster Exhibition : 3F Lobby Booth Exhibition : 3F Emerald Hall/ Diamond Hall Convention Center 4F Swan Room Restroom Board Room LOBBY CONNECTION BRIDGE Exhibition 3 2(M) Peacock F&B Office Grand Ballroom Room C Covention Hall Room AI Room AII Room C Congress Kit VIP Registration VIP Lounge Book Store Information Board Room AI Room AII Room B Room C Preview Meeting Room Secretariat Booth Exhibition : 4F Convention Hall : 4F Convention Hall : 4F Convention Hall : Grand Ballroom, 2F Hotel : Peacock Room : Swan Room : Board Room : The Front of Grand Ballroom, 2F Hotel 6

Daily Program Main Theme: Treatment of Prediabetes and Metabolic Syndrome May 10 (Thu) 15:00~17:00 Registration 17:00~18:00 B Satellite Symposium I The Introduction of a New Era in the Management of Patients with Type 2 Diabetes DPP-4 Inhibitors: a New Class of Oral Agents to Treat Patients with Type 2 Diabetes Achieving the Superior Treatment Goal for Dyslipidemia Patients with Diabetes: Powerful Evidence of Inhibiting two Sources of Cholesterol in "VYTAL Study" 18:00~19:00 B Satellite Symposium II Diabetic Heart, Diabetic Cardiomyopathy: the Search for a Unifying Hypothesis The Changing Scenario in Diabetes Heart and Its Management 19:00~ Welcome Reception May 11 (Fri) A Gary D. Lopaschuk (University of Alberta, Canada) 07:00~08:00 Breakfast Symposium I B Ideal Basal Insulin, Asian LEAD to prove it 08:00~ Registration Room A, ( AI, AII ) - Convention Hall, 4F Room B - Convention Hall, 4F Room C - Grand Ballroom, 2F Hotel 08:00~09:30 AI Insulin resistance and metabolic syndrome The Role of Mitochondrial Dysfunction in the Metabolic Syndrome and Type 2 Diabetes Kitt F. Petersen (Yale University, USA) Gestational Diabetes And Future Metabolic Syndrome: What Are The Issues? Current Status of Metabolic Syndrome in Korea Boyd E. Metzger (Northwestern University, USA) 08:00~09:30 AII Strategies for pancreatic beta-cell protection and regeneration Involvement of Ca 2+ -Mediated Apoptotic Signals in Palmitate-Induced MIN6N8a Beta Cell Death Immunoprotection of Transplanted Pancreatic Islets Using PEGylation The Gut-pancreas Connection and Its Relevance to Diabetes Josephine M. Egan (National Institute of Health, USA) 7

Daily Program 08:00~09:30 B Special Symposium Innovative technology for diabetes management Rationale Behind Treatment with Insulin Pumps - and Continuous Glucose Monitoring Lristen Norgaard (Hvidovre Hospital, Denmark) Choosing a Path on the Journey to a Fully Automated Closed Loop Insulin Delivery System Garry Steil (Meditronics Minimed, USA) 08:00~09:30 C Clinical Characteristics of Japanese Patients with Type 2 Diabetes From the Results of Japan Diabetes Complications Study (JDCS) Hirohito Sone (Ochanomizu University, Japan) 09:30~09:50 Coffee Break 09:50~10:00 A Opening Address 10:00~11:00 A Plenary Lecture I Cellular Mechanisms of Insulin Resistance in Type 2 Diabetes Mellitus and the Metabolic Syndrome Gerald I. Shulman (Yale University, USA) 11:10~12:40 A Main Symposium I - New Drug Target I Treatment of insulin Resistance Associated with Type 2 Diabetes Mellitus and the Metabolic Syndrome Kitt F. Petersen (Yale University, USA) New Roles of an Old Enzyme: NAD(P)H: Quinone Oxidoreductase 1 as an Interesting Drug Target for Metabolic Syndrome Modulation of Insulin Sensitivity by DGAT1 and Triglyceride Synthesis in Skeletal Muscle Yi-Hao Yu (Columbia University, USA) 11:10~12:40 B Oral Presentation I 11:10~12:40 C Diabetes in young women 12:40~13:00 A 8

Room A, ( AI, AII ) - Convention Hall, 4F Room B - Convention Hall, 4F Room C - Grand Ballroom, 2F Hotel 3L - 3F Lobby 13:00~14:00 A Luncheon Lecture I "Where Do We Go from Here" in Lipid Management 13:00~14:00 C Luncheon Lecture II A 14:00~15:00 Plenary Lecture II Mothers with Diabetes, Obesity or Malnutrition Have Offspring With Metabolic Syndrome. Can Similar Mechanisms Be Involved? Boyd E. Metzger (Northwestern University, USA) 15:10~17:10 AI Highlight Oral Session I 15:10~17:10 AII Highlight Oral Session II 15:10~17:10 B Main Symposium II - Non-Pharmacological Treatment Novel Mediators of Skeletal Muscle Metabolism: AMPK, LKB1 and TRB3 Dietary Management For Non-Diabetic and Diabetic Obese Patients Laurie J. Goodyear (Harvard University, USA) 15:10~16:40 C 17:10~17:30 Coffee Break 17:30~19:00 3L 19:00~ C May 12 (Sat) B 07:00~08:00 Breakfast Symposium II Recent Outcome Trials and Their Impact On the Paradigm of Diabetes Management: The Role of Thiazolidinediones in Preventing Disease Progression Peter Grant (University of Leeds, UK) 08:00~ Registration 9

Daily Program 08:00~09:00 AI Diabetes in Korea 2007, 1st Edition 08:00~09:00 AII Mitochondrial Oxidative Dysfunction in the Diabetic Macrovascular Complications Anti-Oxidative and Anti-inflammatory Effects of Phosphodiesterase Type III Inhibitor -Lipoic Acid Suppresses Endothelial Cell Senescence by Elevating Nitric Oxide Production 08:00~09:00 B Oral Presentation II 08:00~09:00 C Sponsored Special Lecture Clinical Endocrinology of DPP-4 Inhibitors 09:10~11:10 A Main Symposium III - Pharmacological Treatment I The Role of the Endocannabinoid System in Food Intake and Metabolic Regulation: Basic and Clinical Concepts Gary Wittert (University of Adelaide, Australia) The Optimizing Strategies to Treat Obesity and Metabolic Syndrome for Korean Obese Patients Understanding Incretins and the Role of Improving Metabolic Syndrome Potential of the New DPP 4 Inhibitors in Metabolic Syndrome 09:10~11:10 B Oral Presentation III 09:10~11:10 C 11:10~11:30 Coffee Break 11:30~11:50 A 10

Room A, ( AI, AII ) - Convention Hall, 4F Room B - Convention Hall, 4F Room C - Grand Ballroom, 2F Hotel 11:50~12:10 A 12:10~13:10 A Luncheon Lecture III Levemir : Weighing the Evidence from Clinical Trials Practice Per Clauson (Novo Nordisk Japan, Japan) 12:10~13:10 C Luncheon Lecture IV To evaluate Diovan (valsartan) for the effects on BP, microalbuminuria in Korean type 2 DM patients 13:10~14:10 A Plenary Lecture III Selective Vascular Insulin Resistance: Concepts for Cardiovascular Risks in Diabetes and Metabolic Syndrome George L. King (Harvard University, USA) 14:20~16:20 AI Main Symposium IV - Pharmacological Treatment II Insulin Resistance, Type 2 Diabetes and Cardiovascular Disease: The Role of Insulin Sensitisers Peter Grant (University of Leeds, UK) Angiotensin Receptor Blockers: New Considerations of Their Mechanisms of Action in Focus of Treatment of the Metabolic Syndrome Bobby V. Khan (Emory University, USA) Role of Lipid-Lowering Drugs in Managing CVD Risk in Diabetes and Metabolic Syndrome Paul N. Durrington (University of Manchester, UK) Metabolic Dysregulation as a Cause for Dysfunction of the Heart in Diabetes and Obesity: Is This a Potential Target for Therapy? Gary D. Lopaschuk (University of Alberta, Canada) 14:20~16:20 AII Main Symposium V - New Drug Target II Ceramide Modulates Lipid and Glucose Metabolism in Cardiovascular System: New Therapeutic Target for Cardiovascular Diseases Columbia University, USA) Pyruvate Dehydrogenase Kinase 4 as a Major Determinant of Skeletal Muscle Insulin Sensitivity (University of Southern California, USA) Enhancing Fat oxidation and Inhibiting Fat Synthesis May Offer Potential Therapeutic Strategies for Obesity and the Metabolic Syndrome Yale University, USA) The Molecular Targets for the Treatment of Metabolic Syndrome 14:20~16:20 B 11 07

C O N T E N T S Plenary Lecture I 41 Cellular Mechanisms of Insulin Resistance in Type 2 Diabetes Mellitus and the Metabolic Syndrome Gerald I. Shulman (Yale University, USA) Plenary Lecture II 45 Mothers with Diabetes, Obesity or Malnutrition Have Offspring With Metabolic Syndrome. Can Similar Mechanisms Be Involved? Boyd E. Metzger (Northwestern University, USA) Plenary Lecture III 49 Selective Vascular Insulin Resistance: Concepts for Cardiovascular Risks in Diabetes and Metabolic Syndrome George L. King (Harvard University, USA) Special Symposium 53 Innovative Technology for Diabetes Management Rationale Behind Treatment with Insulin Pumps - and Continuous Glucose Monitoring Lristen Norgaard (Hvidovre Hospital, USA) Choosing a Path on the Journey to a Fully Automated Closed Loop Insulin Delivery System Garry Steil (Meditronics Minimed, USA) Main Symposium I - New Drug Target I 59 Treatment of insulin Resistance Associated with Type 2 Diabetes Mellitus and the Metabolic Syndrome Kitt F. Petersen (Yale University, USA) New Roles of an Old Enzyme: NAD(P)H: Quinone Oxidoreductase 1 as an Interesting Drug Target for Metabolic Syndrome Modulation of Insulin Sensitivity by DGAT1 and Triglyceride Synthesis in Skeletal Muscle Yi-Hao Yu (Columbia University, USA) Main Symposium II -Non-Pharmacological Treatment 65 Novel Mediators of Skeletal Muscle Metabolism: AMPK, LKB1 and TRB3 Laurie J. Goodyear (Harvard University, USA) Dietary Management For Non-Diabetic and Diabetic Obese Patients 12

Main Symposium III - Pharmacological Treatment I 73 The Role of the Endocannabinoid System in Food Intake and Metabolic Regulation: Basic and Clinical Concepts Gary Wittert (University of Adelaide, Australia) The Optimizing Strategies to Treat Obesity and Metabolic Syndrome for Korean Obese Patients Understanding Incretins and the Role of Improving Metabolic Syndrome Potential of the New DPP 4 Inhibitors in Metabolic Syndrome Main Symposium IV -Pharmacological Treatment II 81 Insulin Resistance, Type 2 Diabetes and Cardiovascular Disease: The Role of Insulin Sensitisers Peter Grant(University of Leeds, UK) Angiotensin Receptor Blockers: New Considerations of Their Mechanisms of Action in Focus of Treatment of the Metabolic Syndrome Bobby V. Khan(Emory University, USA) Role of Lipid-Lowering Drugs in Managing CVD Risk in Diabetes and Metabolic Syndrome Paul N. Durrington(University of Manchester, UK) Metabolic Dysregulation as a Cause for Dysfunction of the Heart in Diabetes and Obesity: Is This a Potential Target for Therapy? Gary D. Lopaschuk(University of Alberta, Canada) Main Symposium V - New Drug Target II 89 Ceramide Modulates Lipid and Glucose Metabolism in Cardiovascular System: New Therapeutic Target for Cardiovascular Diseases Columbia University, USA) Pyruvate Dehydrogenase Kinase 4 as a Major Determinant of Skeletal Muscle Insulin Sensitivity (University of Southern California, USA) Enhancing Fat oxidation and Inhibiting Fat Synthesis May Offer Potential Therapeutic Strategies for Obesity and the Metabolic Syndrome Yale University, USA) The Molecular Targets for the Treatment of Metabolic Syndrome 95 Diabetes in Young Women 13

C O N T E N T S 115 135 155 Clinical Characteristics of Japanese Patients with Type 2 Diabetes From the Results of Japan Diabetes Complications Study (JDCS) Hirohito Sone (Ochanomizu University, Japan) 167 Diabetes in Korea 2007, 1st Edition Insulin Resistance and Metabolic Syndrome 183 The Role of Mitochondrial Dysfunction in the Metabolic Syndrome and Type 2 Diabetes Kitt F. Petersen (Yale University, USA) Gestational Diabetes And Future Metabolic Syndrome: What Are The Issues? Current status of metabolic syndrome in Korea Boyd E. Metzger (Northwestern University, USA) 14

Strategies for Pancreatic Beta-Cell Protection and Regeneration 189 Involvement of Ca 2+ -Mediated Apoptotic Signals in Palmitate-Induced MIN6N8a Beta Cell Death Immunoprotection of Transplanted Pancreatic Islets Using PEGylation The Gut-pancreas Connection and Its relevance to Diabetes Josephine M. Egan (National Institute of Health, USA) 197 Mitochondrial Oxidative Dysfunction in the Diabetic Macrovascular Complications Anti-oxidative and Anti-inflammatory Effects of Phosphodiesterase Type III Inhibitor -Lipoic Acid Suppresses Endothelial Cell Senescence by Elevating Nitric Oxide Production 203 Satellite Symposium I 221 The Introduction of a New Era in the Management of Patients with Type 2 Diabetes DPP-4 Inhibitors: a New Class of Oral Agents to Treat Patients with Type 2 Diabetes Comparison of Sonoporation with Cationic Gene Carriers in In-Vitro Non-Viral Gene Therapy Using VEGF (Vascular Endothelial Growth Factor) Plasmid DNA 15

C O N T E N T S Satellite Symposium II 225 Diabetic Heart, Diabetic Cardiomyopathy: the Search for a Unifying Hypothesis The Changing Scenario in Diabetes Heart and Its Management Gary D. Lopaschuk (University of Alberta, Canada) Breakfast Symposium I Ideal Basal Insulin, Asian LEAD to prove it 229 Breakfast Symposium II 233 Recent Outcome Trials and Their Impact On the Paradigm of Diabetes Management: The Role of Thiazolidinediones in Preventing Disease Progression Peter Grant (University of Leeds, UK) Luncheon Lecture I Where Do We Go from Here in Lipid Management 237 Luncheon Lecture II 241 Luncheon Lecture III Levemir : Weighing the Evidence from Clinical Trials Practice Per Clauson (Novo Nordisk Japan, Japan) 247 Luncheon Lecture IV 249 To evaluate Diovan (valsartan) for the effects on BP, microalbuminuria in Korean type 2 DM patients Sponsored Special Lecture Clinical Endocrinology of DPP-4 Inhibitors 253 16

Highlight Oral Session Highlight Oral Session I (15:10~17:10, May 11 FRI, Room A(I)) Chair Persons: Sung Hee Ihm, Yeon Ah Sung 1 Risk factors of Peripheral Arterial Disease for type 2 diabetic patients in Taiwan National Taiwan University Hospital 1 Yi-Der Jiang 1 2 The Prevalence and Clinical Characteristics of Type 2 Diabetic Patients with Non-Albuminuric Renal Insufficiency Seoul National University Hospital Internal Medicine 1 JH Ahn 1 *, MK Moon 1, JH Kim 1, SH Choi 1, S Lim 1, HC Jang 1, KS Park 1, SY Kim 1, HK Lee1, YM Cho 1 3 Plasma Alanine Aminotransferase and Aamma-Alutamyltranspeptidase are Associated with Diabetes Bellitus and Metabolic Syndrome: An Aged Population Based Cohort Study Department of Internal Medicine, Seoul National University Bundang Hospital 1 Ji Won Yoon 1 *, Yun Hyi Ku 1, Jee Hyun An 1, Hwa Young Ahn 1, Hoon Sung Choi 1, Sung Hee Choi 1, Soo Lim 1, Young Joo Park 1, Hak Chul Jang 1 4 2-h Post-loading Glucose Is Predominantly Correlated with Serum CRP in a Large Population of Chinese with Diabetes, Intermediate Hyperglycemia and Normalglycemia Shanghai Clinical Center for Endocrine and Metabolic Diseases, Division of Endocrinology and Metabolism, E-Institutes of Shanghai Universities, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, China 1, Center for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, China 2, Baoshan District Center for Disease Control and Prevention, China 3, Shanghai Municipal Center of Disease Control and Prevention, China 4, Min Xu 1, Ji-Guang Wang 2, Xin-Jun Wang 1, Yun Huang 1, Qi Cheng 2, Hong-Er Huang 3, Rui Li 4, Li Huo 1, Meng Dai 1, Xiao-Ying Li 1, Guang Ning 1 5 Prevalence of Glucose Intolerance and Metabolic Syndrome Features in Prior Gestational Diabetes Mellitus (GDM) Women in Penang Hospital Endocrine Unit, Medical Department, Penang Hospital 1, Penang Medical College 2, Nuclear Medicine Department, Penang Hospital 3 Shanty Velaiutham 1, Chong Hui Khaw 1, Shueh Lin Lim 1, Malik Mumtaz 2, Nor Azizah Aziz 1, Mohamed Ali Abdul Kader 3, Amir S Khir 2 17

6 Prevalence of Metabolic Syndrome by IDF Definition anong Adults 25 Years and above in Urban Karachi- Pakistan BIDE 1, DAP 2, Interactive Communications 3, Lyari Community Development Project 4 Asher Fawwad 1, Abdul Bsit 1, A Samad Shera 2, Aamir Khan 3, Javed Ismail 3, Nasreen Molla 3, Ahsanullah Khan 3, Imran Khan 4 7 Mutation Screening of HNF-1 Gene in Korean Women with GDM Cheil General Hospital & Women's Healthcare Center, Kwandong University College of Medicine, Korea 1, Center for genome science, National Genome Research Institute, NIH Korea 2 Hun-Sung Kim 1 *, Sun-Hee Whang 1, Eun-Sun Choi 1, So-Young Park 1, Chang-Hoon Yim 1, Ki-Ok Han 1, Hyun-Koo Yoon 1, Kyung-Seon Kim 2, Jeong Bok 2, Jong-Young Lee 2, Sung-Hoon Kim 1 8 Differences of the Insulin Resistance and Insulin Secretory Patterns Based on the OGTT In Newly Diagnosed Subjects with IFG and IGT Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University 1, Research Institute of Endocrinology, Kyung Hee University 2 SY Rhee 1 *, YJ Yoon 2, KS Suh 2, MK Kwon 1, S Chon 1, I-K Jeong 1, S Oh 1, KJ Ahn 1, HY Chung 1, SW Kim 1, J-W Kim 1, YS Kim 1, J-T Woo 1 9 The Association of Educational Backgrounds with Cardiovascular Risk Factors and Metabolic Syndrome: A Study of Middle-Aged Koreans in a Health Promotion Center Department of Internal Medicine, Ilsan-Paik Hospital, Inje University College of Medicine 1, Center for Health Promotion, Samsung Medical Center, Sungkyunkwan University School of Medicine 2, Samsung Medical Center, Sungkyunkwan University of Medicine 3 Division of Endocrinology and Metabolism, Department of Medicine, Sam DJ Kim 1*, JH Noh 1, JH Jee 2, KW Kim 3 Discrepancy of the Prevalence of Metabolic Syndrome between the ATP III and IDF Criteria in Korean Type 2 Diabetes PatientsThe Prevalence College of Medicine, KyungHee University 1, College of Medicine, Hallym University 2, College of Medicine, SungKyunKwan University 3, College of Medicine, Seoul National University 4, College of Medicine, Inje University 5, College of Medicine, Yonsei University 6, Colleg 7 SY Rhee 1 *, S Oh 1, JM Yu 2, JH Jee 3, MK Lee 3, KS Park 4, HK Lee 4, KH Lim 5, ES Kang 6, HC Lee 6, YS Kim 7, JT Kim 8, SH Shinn 8, WH Choi 9, YS Kim 1 10 18

11 Prevalence of Metabolic Syndrome Using The NCEP ATP III Modified Asian Criteria among Population in Five Regions of Jakarta Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Indonesia 1 Research and Health Development, Ministry of Health, Republic of Indonesia 2 Purnamasari D 1, Soewondo P 1, Rahajeng E 2, Waspadji S 1, Soegondo S 1, Yunir E 1 12 Prevalence of Metabolic Syndrome Using The NCEP ATP III Modified Asian Criteria among Population in Five Regions of Jakarta Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Indonesia 1 Research and Health Development, Ministry of Health, Republic of Indonesia 2 Purnamasari D 1, Soewondo P 1, Rahajeng E 2, Waspadji S 1, Soegondo S 1, Yunir E 1 13 The Predictive Cutoff Values and the Correlation of Serum -Glutamyltransferase for Metabolic Syndrome, Diabetes Mellitus and Coronary Heart Disease in Korean Subjects Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine 1, Institute of Medical Research, Kangbuk Samsung Hospital 2 Se-Yeon Kim 2, Hee-Soon Park 2, Sook-Kyung Cho 1, Jong-Chul Won 1, Chan-Hee Jung 1, Cheol-Young Park 1, Won-Young Lee 1, Ki-Won Oh 1, Sung-Woo Park 1, Sun-Woo Kim1, Eun-Jung Rhee 1* Highlight Oral Session II (15:10~17:10, May 11 FRI, Room A(II)) Chair Persons: Hak Chul Jang, Nam Han Cho 14 Peripheral Nerve Protective Effect of COMP-Angiopoietin-1 in db/db Diabetic Mice Endocrinology and metabolism and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School 1, Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicin 2 HY Jin 1 *, P.Han 1, SY Kim 1, JH Park 1, HS Baek 1, S Lee 2, GY Koh 3, TS Park 1 15 -Lipoic Acid Prevents Albuminuria and Activates Renal AMP-Activated Protein Kinase in Diabetic OLETF Rats Division of Endocrinology and Metabolism, Department of Internal Medicine Ulsan University 1 EH Cho 1 *, WG Kim 1, BJ Kim 1, EH Jeong 1, HJ Lee 1, EH Koh 1, MS Kim 1, JY Park 1, KU Lee 1 19

16 Exclusion of APOM as candidate gene for Type 2 Diabetes in a Hong Kong Chinese population Department of Biochemistry, The Chinese University of Hong Kong 1, Molecular Biotechnology Programme, The Chinese University of Hong Kong 2, Department of Medicine and Therapeutics, The Chinese University of Hong Kong 3 Junwei Zhou 1, Maggie Ng 1, Ming Yin Lui 1, Hua Geng 1, Pui Ying Law 1, Juliana Chan 1, Yuan Yuan Ho 1 17 Islet Cell Differentiation In Liver by Combinatorial Expression of Transcription Factors Neurogenin-3, BETA2, and RIPE3b1 Endocrinology, Research Institute of Endocrinology, and Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine 1, Endocrinology, National Health Insurance Corporation, Ilsan Hospital 2 Taewoong Noh 1 *, Mi Ae Cho 1, Jong Suk Park 1, Yumie Rhee 1, Eun Seok Kang 1, Chul Woo Ahn 1, Bong Soo Cha 1, Sung Kil Lim 1, Kyung Rae Kim 1, Hyun Chul Lee 1, Young-Duk Song 2, Eun Jig Lee 1 18 Changes of Self-Care Behavior Trends in Diabetes Share-Care Network in Taiwan National Taiwan University Hospital 1 Yi-Der Jiang 1, Chiou-Shiang Wang 1 *, I-Ching Wang 1 19 Hypoglycemic effect of vinegar on the Streptozotocin-induced Type 1 Diabetic Rats The Chinese University of Hong Kong 1 Xuemei Gu 1 *, Hailu Zhao 1, Xun Zhu 1, Yi Sui 1, Jing Guan 1, Juliana CN Chan 1, Peter CY Tong 1 20 Effect of PPAR- Agonist on Expression of Visfatin, Adiponectin and Resistin in Rat Adipose Tissue and 3T3- L1 Adipocytes Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University 1 HJ Yoo 1 *, KM Choi 1, HS Kim 1, TN Kim 1, SJ Yang 1, DJ Kim 1, JR Park 1, SY Park 1, EJ Lee 1, HY Kim 1, JA Seo 1, SK Kim 1, NH Kim 1, DS Choi 1, SH Baik 1 21 Fenofibrate Suppressed the Gene Expressions of Gluconeogenic Enzyme in the Liver Department of Internal Medicine, Medical College of Dong-A University 1, Department of Pharmacology, Medical College of Dong-A University 2, Depart of Medicine, The Graduate School of Dong-A University 3, Department of Internal Medicine, Wallace Memorial Baptist 4 Kyung Il Lee 4 *, En Hui Seo 2, Mi Sun Kim 2, Ying Han 3, Su Kyung Park 1, Mi- Kyoung Park 1, Hye-Jeong Lee 2, Duk Kyu Kim 1 20

O 22 Clusterin Suppression of Reactive Oxygen Species Induced by TNF- Department of Internal Medicine, Kyungpook National University School of Medicine 1, Department of Internal Medicine, Keimyung University School of Medicine 2 YJ Doh 1 *, EK Yoo 1, HJ Kim 1, HJ Lee 1, EJ Kim 1, SJ Lee 1, BW Kim 1, JK Kim 1, SR Kim 1, SS Moon 1, HS Kim 2, KG Park 2, IK Lee 1 23 Age and Insulin Treatment in OLETF Rat Skeletal Muscle Leads to Change of Myosin Heavy Chain Isoform The Division of Endocrinology & Metabolism, Department of Internal Medicine, The Catholic University of Korea 1, Immunology & Cell Biology Core Laboratory, Catholic Research Institutes of Medical Science 2, Catholic Institute of Ubiquitous Healthcare 3 SM Park 1 *, OK Hong 2, YH Choi 3, HS Kwon 1, JM Lee 1, KH Song 1, KH Yoon1, SK Kang 1, SJ Yoo 1 24 Hypoxia-Inducible Gene Expression in Islets for Islet Transplantation Department of Internal Medicine, College of Medicine, Hallym University 1, Department of Bioengineering, College of Engineering, Hanyang University 2, Department of Internal Medicine, Seoul National University College of Medicine 3 HA Kim 2, BW Lee 1 *, JH Kim 3, KS Park 3, M Lee 2, DC Kang 1, SH lhm 1 25 Searching the Candidate mirnas Related with Glucolipotoxicity-Induced Beta-Cell Dysfunction by mirna Chip Analysis Department of Endocrinology & Metabolism, College of Medicine, The Catholic University of Korea 1 JW Kim 1 *, SH Ko 1, JHCho 1, SJ Yoo 1, YB Ahn 1, BY Cha 1, HY Son 1, KH Yoon 1 21

Oral Presentation Oral Presentation I (15:10~17:10, May 11 FRI, Room A(I)) 1 Relation of C-Reactive Protein to Framingham Risk Score and UKPDS Risk Engine in Korean Patients with Type 2 Diabetes Dong-Mee Lim 2, Keun-Yong Park 2, Dae-Hoo Lee 1, Gwanpyo Koh 1 * 2 Homocysteine as a Risk Factor for Microalbuminuria Division of Endocrinology and metabolism, Department of Internal Medicine 1 EH Cho 1 *, WG Kim 1, BJ Kim 1, EH Jeong 1, HJ Lee 1, EH Koh 1, MS Kim 1, JY Park 1, KU Lee 1 3 4 Effects of N-Acetylcysteine, Quercetin, and Apocynin on Diabetic Nephropathy in OLETF Rats * 5 * 6 * 7 Peroxisome Proliferator-Activated Receptor-Gamma (PPAR- ) Agonists Enhanced Endothelial Cell Migration and Decreased Vascular Adhesion Molecules in Wound Healing Model in Vitro 22

8 -Lipoic Acid Inhibits Matrix Metalloproteinase-9 Expression by Inhibiting NF- B Transcriptional Activity Department of Internal Medicine, Kyungpook National University School of Medicine 1,Department of Internal Medicine, Keimyung University School of Medicine 2 9 Cystatin C Rises Earlier and is More Accurate Serum Marker than Creatinine in the Prediction of Type 2 Diabetic Nephropathy. Hallym medical school 1 J.H. Yang 1 *, H.J. Yoo 1, J.M. Yu 1, E.K. Hong 1, H.R. Lee 1, M.G. Choi 1, O.H. Ryu 1, D.M Kim 1, H.K. Kim 1, S.H. Ihm 1, S.J. Lee 1, C.S. Kim 1, J.K. Kang 1, B.W. Lee 1 Highlight Oral Session II (08:00~09:00, May 12 SAT, Room B) 10 Low Glucose Increases Oxidative Stress and Impacts GSIS (Glucose Stimulated Insulin Secretion) in INS-1 Cells and Rat Islets 11 Glucagon-Like Peptide 1 Increases Mitochondrial Biogenesis and Function in INS-1 Cells 12 Differentiation of Insulin Producing Cells from Human Embryonic Stem Cells 13 Exendin-4-Induced Cyclin D1 Expression in INS-1 Cells (Focusing on the Transcription Factors) 14 Mitochondrial Dysfunction Decreases the Interaction of Glucokinase with Mitochondria through Downregulation of Glucokinase, Leads to Apoptosis of Pancreatic -Cells 23

15 Highlight Oral Session II (09:00~11:10, May 12 SAT, Room B) 16 The Relationship between Plasma Glucose Concentration and HbA1c Based on the Continuous Glucose Monitoring System Department of Endocrinology and Metabolism, College of MEdicine, Kyung Hee University 1, Research Institute of Endocrinology, Kyung Hee University 2 SY Rhee 1 *, MK Kwon 1, S Chon 1, I-K Jeong 1, S Oh 1, KJ Ahn 1, HY Chung 1, SW Kim 1, J-W Kim 1, YS Kim 1, J-T Woo 1 17 Successful Xenogenic Islet Transplantation with Alginate Microcapsules 18 High Carbohydrate Diet and Total Daily Calories Induce Glucose Abnormalities in Korea Department of Endocrinology, Gachon University of Medicine and Science 1, Preventive Medicine, Gachon University of Medicine and Science 2, Graduated School of Public Health, Gachon University of Medicine and Science 3 SM Yang 1 *, KY Lee 1, YS Kim 1, KJ Jeong 1, JI Lee 1, YJ Back 1, J S Im 2, J Yim 2, ST Youn 3, IB Park 1 19 Latent Autoimmune Diabetes in Adults Should be Suspected in Korean Diabetic Patients with Low C- peptide Level and without Metabolic Syndrome Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea 1 JH Kim 1, JH Cho 1, HS Kwon 1, SJ Yoo 1, KH Yoon 1, BY Cha 1, HY Son 1, SH Lee 1 * 20 24

21 Association with Adiponectin Receptor 1 (AdipoR1) Polymorphisms and Obesity Related-Phenotypes in Korean Adults and Children. 22 Effect of Exercise on the Adiponectin and Retinol Binding Protein 4 Concentration in Young and Middle Aged Women Seoul National University College of Medicine, Department of Internal Medicine 1 Soo Lim 1, Sung Hee Choi 1, Kyong Soo Park 1, Hong Kyu Lee 1, Hak Chul Jang 1 23 Effects of Rosiglitazone on Body Fat Distribution and Insulin Sensitivity in Korean Type 2 Diabetic Patients Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine 1, Department of Internal Medicine, College of Medicine, Yonsei University 2, Divison of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea 3 24 The Effect on Body Composition with Intensive Glycemic Control Using Insulin and Life style Modification in Poorly Controlled Type 2 Diabetic Patients Department of Endocrinology and metabolism, The Catholic University of Korea 1, Department of Preventive Medicine, The Catholic University of Korea 2 JM Lee 1 *, JS Kim 1, WR Jung 1, HS Hwang 1, SM Park 1, SS Lee 1, YM Park 2, SR Kim 1, GH Yun 1, MI Kang 1, BY Cha 1, GW Lee 1, HY Son 1, SK Kang 1, SJ Yoo 1 25 Glucotoxicity in Pancreatic Beta Cell is Mediated by ER Stress-Associated Activation of ATF 6 Department of Internal medicine, Keimyung University School of Medicine 1, Department of Internal medicine, Kyungpook National University School of Medicine 2 Mi-Kyung Kim 1 *, Hye-Soon Kim 1, Ho-Chan Cho 1, Hye-Young Seo 1, Kyeong-Min Lee 1, Ae-kyung Min 1, Yong-Deuk Kim 1, Bo- Wan Kim 2, Jung-Guk Kim 2, In-Kyu Lee 2, Keun-Gyu Park 1 26 27 Novel Anorexigenic Effect of Clusterin (Apoprotein J) 25

Session I (17:30~19:00, May 11 FRI, 3F) 1 2 3 Relationship between Serum Bilirubin Levels and Subclinical Coronary Atherosclerosis in Patients with Type 2 Diabetes 4 Visceral Adiposity and Leptin are Independently Associated with CRP in Korean Type 2 Diabetic Patients Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea 1 HY Jung 1 *, JE Yoon 1, MH Cho 1, HJ Kim 1, JS Nam 1, ES Kang 1, YM Rhee 1, CW Ahn 1, BS Cha 1, EJ Lee 1, SK Lim 1, KR Kim 1, HC Lee 1, JS Park 1 5 Prevalence and Clinical Characteristics of Aspirin Resistance in the Korean Patients with Type 2 Diabetes Mellitus 26

Session II (17:30~19:00, May 11 FRI, 3F) 6 Improvement of Glycemic Control with Time After Autologous Islet Transplantation in Patients with Partial Pancreatectomy Due to Benign Pancreatic Tumors 7 S-Adenosyl-L-Methionine Improved Glycemic Control in Type 2 Diabetic Subjects Department of Internal Medicine, Seoul National University College of Medicine 1, Seoul National University Boramae Hospital 2, Department of Pharmacology, Seoul National University College of Medicine Department of Internal Medicine 3 MK Moon 1 *, Min Kim 1, SH Koh 3, P Swovoda 3, MH Chung 3, YM Cho 1, YJ Park 1, H Choi 1, HC Jang 1, SY Kim 1, KS Park 1, HK Lee 1 8 A Comparison of between Cystatin C-and Creatinine-Based Methods for the Estimation of Glomerular Filtration Rate in Diabetic Patients 9 ALT-711 Attenuates Diabetic Renal Injury through Antioxidant Effect 10 Imatinib Mesylate Induces Remission of Type 2 Diabetes Sungkyunkwan University School of Medicine 1, Korea Research Institute of Chemical Technology 2 MS Han 1 *, KW Chung 1, HG Cheon 2,SD Rhee 2, MK Lee 1, KW Kim 1, MS Lee 1 11 Validity of Color-Doppler Ultrasonography for Diagnosis of Peripheral Arterial Disease in Diabetes Mellitus with Normal Ankle-Brachial Index 27

Session III (17:30~19:00, May 11 FRI, 3F) 12 The Course of Non Alcoholic Fatty Liver Disease (NAFLD) in Non- Obese Subjects; A Longitudinal Observation Study 13 14 15 16 17 The Changes of Central Aortic Pulse Wave Analysis in Metabolic Syndrome(MS) Session IV (17:30~19:00, May 11 FRI, 3F) 18 28

19 Heme Oxygenase-1 Overexpression Prevents Endoplasmic Reticulum Stress by High Glucose in INS-1 Cells 20 Transcriptional Regulation of KLF4 on Ghrelin, Appetite Hormone, in AGS Human Gastric Cancer Cells 21 22 23 PPAR- is Aassociated with Glucose Induced Insulin Secretion (GSIS) and Interaction with BETA2/NeuroD Session V (17:30~19:00, May 11 FRI, 3F) 24 25 Effects of Physical Activity on Glucose Tolerance among Type 2 Diabetic Patients 29

26 27 Usefulness of HbA1C for Monitoring the Development of Diabetes in High-Risk Patients 28 30

1 The Biochemical Markers of Coronary Heart Disease Correlates Better to Metabolic Syndrome Defined by WHO than by NCEP-ATP III or IDF in Korean Type 2 Diabetes Patients 2 Matrix Metalloproteinase 1 Gene Promoter Polymorphisms are Associated with Myocardial Infarction 3 4 5 6 4-Phenyl Butyric Acid (4PBA) Alleviate Palmitate-Induced Endoplasmic Reticulum Stress and Apoptosis 7 8 9 31

10 11 Clinical Usefulness of Cardio Ankle Vascular Index for Predicting Vascular Complications in Relatively Well Controlled Type 2 Diabetic Patients JH Kim 1 *, HS Kwon 1, SH Lee 1, MJ Kang 1, KH Yoon 1, BY Cha 1, HY Son 1 12 Effect of Adiponectin on Palmitate-Induced Human Umbilical Vein Endothelial Cells Apoptosis Department of Physiology, College of Medicine, Yeungnam University, Daegu 1, Aging-associated vascular research center, College of Medicine, Yeungnam University, Daegu 2 YW Kim 1, JY Kim 1, SY Park 11, JE Kim 1 * 13 Relationship between Serum Magnesium and HDL-Cholesterol Levels in Diabetic Patients with Ischemic Heart Disease Department of internal medicine, Hong Ik Hospital 1 HS Chung 1, YW Kim 1, MJ Kim 1 * 14 Adipokines and Carotid Intima-Media Thickness in Type 2 Diabetic Patients Department of Internal Medicine SoonChunHyang University College of Medicine 1 JH Jung 1, KO Lee 1, JO Mok 1, HK Park 1, YJ Kim 1, CH kim 1, SJ Kim 1, DW Byun 1, KI Suh 1, MH Yoo 1, MO Roh 1 * 15 16 17 32

18 Economic Impact of the Information Technology-Based Diabetes Management System on Type 2 Diabetes 19 20 21 22 23 24 Usual Delay in Sample Processing Can Underestimate Detection of Prediabetes JG Kang 1 *, HR Lee 1, OH Ryu 1, BW Lee 1, CS Kim 1, SJ Lee 1, EG Hong 1, HK Kim1, JM Yu 1, DM Kim 1, SH Ihm 1, MG Choi 1, HJ Yoo 1, MH Cho 3, CY Park 2 25 The Effect of Benfotiamine on High Sensitivity-CRP (hs-crp) Level in Patients with Type 2 Diabetes Mellitus Hallym University, College of Medicine 1, National Medical Center 2 HK Kim 1, HW Nam 2, JK Kang 1, BW Lee 1, SJ Lee 1, EK Hong 1, JM Yoo 1, SH Ihm 1, MK Choi 1, HJ Yoo 1, DM KIm 1 * 33

26 High Glucose and Free Fatty Acid Damage Endothelial Cells Via Stimulating NADPH Oxidase-Induced Superoxide Production from Neutrophils Department of Internal Medicine, School of Medicine, Pusan National University 1 JH Kwon 1 *, YS An 1, YH Kang 1, IJ Kim 1, YK Kim 1, SM Son 1 27 Safety, Tolerability and Efficacy of Rosiglitazone (Avandia(tm)) in Patients with Type 2 Diabetes: Data from a Postmarketing Surveillance in Korea GlaxoSmithKline Korea, Medical Department 1 OJ Jung 1 *, YI Kim 1, NH Kwon 1, W Choi 1, YS Lee 1 28 29 30 31 32 33 34

34 35 36 37 38 39 Cloning of Effective Novel Mini-Circle Plasmid DNA for the Non-Viral EGF Gene Therapy to the Diabetic Cutaneous Ulcer Molecular Therapy Lab., Paik Memorial Institute for Clinical Research 1, Department of Internal Medicine, Pusan Paik Hospital, College of Medicine, Inje University 2, Maryknoll General Hospital 3 40 Association between Endogenous Secretory RAGE, Inflammatory Markers and Arterial Stiffness 41 35

42 43 44 45 46 47 Functional Eythropoietin Dficiency in Type 2 Diabetics with Anemia 48 Hypoadiponectinemia is Strongly Associated with the Risk of Impaired Glucose Metabolism and Type 2 Diabetes in Rural Adult Koreans 49 36

50 Comparison of Sonoporation with Cationic Gene Carriers in In-Vitro Non-Viral Gene Therapy Using VEGF (Vascular Endothelial Growth Factor) Plasmid DNA Molecular Therapy Lab, Paik Memorial Institute for Clinical Research, Department of Endocrinology and Metabolism, Pusan Paik Hospital, Inje University 1, Department of Internal Medicine, Maryknoll General Hospital 2 51 52 53 54 Recurrent Diabetic Muscle Infarction in a Patient with Type 2 Diabetes Department of Internal Medicine, College of Medicine, Dankook University 1, Department of Pathology, College of Medicine, Dankook University 2 YS Yoo 1, DH Kim 1, HK Chung 1, MS Kwon 2, HJ Kim 1 * 55 Associated Factors between the Obesity and Pancreatic Cell Dysfunction in Non Diabetic Normal Young Adults Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University 1, Research Institute of Endocrinology, Kyung Hee University Medical Center 2 S Chon 1 *, MK Kwon 1, SY Rhee 1, IK Jeong 1, SJ Oh 1, KJ Ahn 1, HY Chung 1, SW Kim 1, JW Kim 1, YS Kim 1, JT Woo 1 56 Role of JNK Activation in Pancreatic -Cell Deth by STZ 37

57 Serum Retinol-Binding Protein 4 Levels are Elevated in Nonalcoholic Fatty Liver Disease Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University 1, Department of Biostatistics, College of Medicine, Korea University 2, Department of Endocrinology, Konkuk University 3 JA Seo 1 *, NH Kim 1, SY Park 1, HY Kim 1, OH Ryu 1, KW Lee 1, J Lee 2, DL Kim 3, KM Choi 1, SH Baik 1, DS Choi 1, SG Kim 1 58 59 60 Endothelial Progenitor Cells and MATRIGEL Enhances Engraftment in Subcutaneous Islet Transplantation Department of Internal Medicine, Seoul National University Boramae Hospital 1, Innovative Research Institute for Cell Therapy, Seoul National University Hospital 2, Department of Internal Medicine, Seoul National University College of Medicine 3 SG Park 2, HJ Park 2, J Kang 2, JE Yu 2, KM Hyun 2, KS Park 3, HK Lee 3, JH Kim 1 * 61 Insulin Induction of the Protein Fractions from Korean Mistletoe (Viscum Album Coloratum) Extracts Institute of Bioscience and Technology, Handong Global University 1 Ki Wook Kim 1 *, Seung Hoon Yang 1, Se Joong Kim 1, Hoe Yune Jung 1, Jong Bae Kim 1 62 63 Is White Blood Cell Count Associated with a Worsening of Insulin Sensitivity in Obese People? Subdivision of Endocrinology and Metabolic Intenal Department Sardjito General Hospital/Medical Faculty of Gadjah Mada University Yogyakarta 1 Internal Department Sardjito General Hospital/Medical Faculty of Gadjah Mada University Yogyakarta 2 Bowo Pramono 1, Rizka Humardewayanti 2, Harakati Wangi 2 38

64 Prevalence and Profile of Renal Impairment in New Type-2 Diabetes Mellitus Patients in Endocrinemetabolic Clinic, Cipto Mangunkusumo Hospital Internal Medicine Departement, Faculty of Medicine University of Indonesia 1 Nephrology and Hypertension Division, Internal Medicine Departement, Faculty of Medicine University of Indonesia 2 Metabolic-Endocrine Division, Internal Medicine Departement, Faculty of Medicine University of Indonesia 3 Physchosomatic Division, Internal Medicine Departement, Faculty of Medicine University of Indonesia 4 Triyanti K 1, Suhardjono 2, Soewondo P 3, Shatri H 4 65 In Obese Patients Insulin Resistance Is Not Correlated with Triglyceride But Correlated With Fasting Blood Glucose Sub Division of Endocrinology and Metabolism, Internal Medicine Department Gadjah Mada School of Medicine, Indonesia 1 Luthfan Budi Purnomo 1, Hemi Sinorita 1, Rizka Humardewayanti 1 66 39

Plenary Lecture

The 20 th Spring Congress of Korean Diabetes Association Cellular Mechanisms of Insulin Resistance in Type 2 Diabetes Mellitus and the Metabolic Syndrome Gerald I. Shulman Yale University School of Medicine, USA Despite much work the cellular mechanisms responsible for insulin resistance in type 2 diabetes and the metabolic syndrome remain unknown. In this regard recent studies measuring muscle triglyceride content by biopsy or intramyocellular lipid content by 1H magnetic resonance spectroscopy have shown a strong relationship between intramuscular lipid content and insulin resistance in skeletal muscle. Recent studies have also demonstrated increases in intramyocellular lipid content in insulin resistant offspring of parents with type 2 diabetes suggesting that dysregulation of fatty acid metabolism may be responsible for mediating the insulin resistance in these individuals. Increases in the intramyocellular concentration of fatty acid metabolites in turn have been postulated to activate a serine kinase cascade leading to decreased insulin stimulated insulin receptor substrate- 1 associated phosphatidylinositol 3-kinase activity resulting in reduced glucose transport activity and glycogen synthesis. This presentation will focus on recent studies using noninvasive 13C, 31P and 1H magnetic resonance spectroscopy techniques in humans to examine the mechanism of fatty acid induced hepatic and muscle insulin resistance and more recent studies that have implicated functional defects in mitochondrial activity in the pathogenesis of insulin resistance in young lean insulin resistant individuals who are prone to develop type 2 diabetes and the metabolic syndrome. References Shulman, GI. Cellular Mechanisms of insulin resistance. J. Clin. Invest., 2000;106:171-176 Griffin, ME, Marcucci, MJ, Cline, GW, Bell, K, Barucci, N, Lee, D, Goodyear, LJ, Kraegen, EW, White, MF, Shulman, GI. Free Fatty Acids Induced Insulin Resistance is Associated with Activity of PKCtheta and alterations in the Insulin Signaling Cascade. Diabetes 1999;48:1270-1274. Yu, C, Chen, Y, Zong, H, Wang, Bergeron, R, Kim, J, Cline, G, Cushman, S, Cooney, G, Atcheson, B, White, M, Kraegen, E, Shulman, G.I. Mechanism by which Fatty Acids Inhibit Insulin Activation of IRS-1 Associated Phosphatidylinositol 3-Kinase Activity in Muscle. J. Biol. Chem. 2002;277(52):50230-50236. Weiss, R, Dufour, S, Tksali, S, Tamborlane, W, Petersen, K, Bonadonna, R, Boselli, L, Barbetta, G, Allen, K, Rife, F, Savoye, M, Dziura, J, Sherwin, R, Shulman, G.I., Caprio, S. Pre-type 2 Diabetes in Obese Youth: A Syndrome of Impaired Glucose Tolerance, Severe Insulin Resistance and Altered Myocellular and Abdominal Fat Partitioning. Lancet 2003;362:951-957 Petersen, K, Befroy, D, Dufour, S, Dziura, J, Ariyan, C, Rothman, D, DiPietro, L, Cline, G, Shulman, G.I. Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance. Science. 2003;300:1140-1142. Petersen, K, Dufour, S, Befroy, D., Garcia, R, Shulman, G.I. Impaired Mitochondrial Activity in Insulin Resistant Offspring of Type 2 Diabetics N. Eng. J. Med. 2004;350:664-671 Lowell, B. and Shulman GI. Mitochondrial Dysfunction and Type 2 Diabetes. Science 2005;307:384-387. Petersen, K., Dufour, S., Shulman, G.I. Decreased Insulin-Stimulated ATP Synthesis and Phosphate Transport in Muscle of Insulin Resistant Offspring of Type 2 Diabetic Parents PloS Medicine 2005;2:e233 Morino, K, Petersen, K, Dufour, S, Befroy, D, Frattini, J, Shatzkes, N, Neschen, S, White, M, Bilz, S, Sono, S, Pypaert, M, Shulman, GI. Reduced Mitochondrial Density and Increased IRS-1 Serine Phosphorylation in Muscle of Insulin-Resistant Offspring of Type 2 Diabetic Parents. J Clin Invest 2005;115:3587-3593. 43

Plenary Lecture

The 20 th Spring Congress of Korean Diabetes Association Mothers with Diabetes, Obesity or Malnutrition Have Offspring with Metabolic Syndrome. Can Similar Mechanisms be Involved? Boyd E Metzger Division of Endocrinology, Metabolism & Molecular Medicine, Northwestern University Feinberg School of Medicine, USA Emerging epidemics of obesity and of type 2 diabetes have become evident in the past 15-20 years and they are projected to continue expanding globally in the foreseeable future. The affected individuals are often insulin resistant; they commonly acquire other features of the metabolic syndrome (dyslipidemia, hypertension); and they are at high risk for development of cardiovascular disease. The combined impact of these events on the future health of the population is potentially so great that some have predicted that for the first time in recorded history, the lifespan of the current generation of youth, rather than continuing to increase, may be shorter than that of their parents. Thus, in order to develop effective strategies to prevent these epidemics, it is imperative that we provide insights into their pathogenesis. Much evidence supports the generally held view that both obesity and type 2 diabetes mellitus (T2DM) have a strong polygenic predisposing background and results from ongoing studies in several populations indicate that multiple specific genes potentially make contributions. The very rapid increases in the prevalence of both obesity and T2DM imply that environmental factors also make major contributions to both conditions. Epidemiological and experimental data indicate that changes in lifestyle are critically important contributing factors. Furthermore, there is much evidence that the time of an environmental insult may differ depending when it takes place over the lifecourse of an individual. A large body of evidence dating back to the Dutch Famine of World War II indicates that alteration of the metabolic/nutritional intrauterine environment can have lifelong and transgenerational consequences for the exposed offspring. Data derived from studies in animal models and epidemiological studies and clinical investigations in humans have provided strong evidence that exposure to the intrauterine environment of maternal diabetes can predispose the offspring to obesity and abnormal glucose metabolism and T2DM in later life. The tendency to obesity in newborn infants whose mothers had pre existing or gestational diabetes (GDM) tends to be lost during infancy, but more rapid weight gain tends to become evident by 4-5 years of age and glucose intolerance increases as the puberty linked period of increased insulin resistance becomes evident after 8-9 years of age. Many of the same features have been found in studies of offspring of type 1 DM, T2DM, or GDM, mothers (ODM) suggesting that genetic pre disposition to obesity may not be universal in ODM that become obese and/or have metabolic disturbances. More recently, studies in animals (rodents and primates) that are not genetically predisposed to obesity, indicate that maternal obesity that is brought about by the ingestion of an energy dense, high fat diet before and/or during pregnancy predisposes to obesity, insulin resistance, altered glucose and lipid metabolism and gestational diabetes in the offspring. Some data from human pregnancy suggest that similar events may contribute to obesity in offspring of overweight or obese mothers. Data from epidemiological studies, clinical observations, and animal models also indicate that impaired states of intrauterine nutrition (potentially brought about by many different mechanisms) that result in restriction of fetal growth are associated with increased risks of obesity, cardiovascular disease and T2DM later in life. Evidence is emerging indicating 47

that these propensities may be modified or exacerbated by the nature and amount of postnatal feeding. Thus, offspring of mothers with diabetes, obesity, or impaired nutrient delivery to the developing fetus are at increased risk for obesity and metabolic disturbances in later life. Is it possible that similar mechanisms can be involved in initiating the phenotype in offspring of these apparently quite different maternal conditions? Epigenetic modification represents one mechanism that could be involved. Exciting new data that have been reported by numerous investigators (using a variety of model systems) illustrate that epigenetic changes could mediate many of the long-lasting consequences of alterations in the intrauterine environment. Hyperinsulinism during late fetal development or in early infancy could be another unifying phenomenon. Programming ( hard wiring ) of hypothalamic neural pathways that integrate appetite, satiety, energy expenditure and hormone secretion (insulin, glucagon, gut hormones) continues in late gestation and early infancy, and is modulated by insulin, leptin and other hormonal signals. Exposure of rodent fetuses or suckling pups to hyperinsulinemia leads to altered hypothalamic development. In ODM, fetal hyperinsulinism, resulting from altered nutrient delivery to the fetus (hyperglycemia, hyperaminoacidemia, dyslipidemia?) is strongly associated with the predisposition to childhood obesity and glucose intolerance. Maternal? fetal signals that may mediate alterations associated with maternal obesity are not defined. In rodents, ingestion of a high carbohydrate insulin-stimulating diet during the suckling period instead of high fat, low carbohydrate low-insulinemic breast milk also alters hypothalamic development and is associated with later development of obesity and disturbances of glucose and lipid metabolism. This could hypothetically be implicated in transmitting effects of maternal obesity. Finally, there is some evidence that offering normal nutrients or high carbohydrate rations to growth restricted newborn rodent pups or human infants may be accompanied by hyperinsulinemia, rapid catchup growth in infancy and obesity in during later childhood and adult life. Because of the epidemics of obesity and T2DM described at the outset and the urgent need for preventive interventions, additional animal model, epidemiological and clinical studies are critically needed to better define the links between altered intrauterine metabolic/nutrient exposure and predisposition to metabolic disorders in later life. 48

Plenary Lecture

The 20 th Spring Congress of Korean Diabetes Association Selective Vascular Insulin Resistance: Concepts for Cardiovascular Risks in Diabetes and Metabolic Syndrome George King Joslin Diabetes Center Harvard Medical School, USA Cardiovascular diseases are the major causes of premature mortalities in type 1 and type 2 diabetic patients. In addition, insulin resistance also is an independent risk factor for cardiovascular pathologies in non-diabetic patients. It is likely that metabolic factors, in conjunction with insulin resistance, are increasing the risk for cardiovascular pathologies in patients with diabetes and metabolic syndrome. These factors include hyperglycemia, hyperlipidemia and hypertension. New treatments to lower cholesterol levels and blood pressure have significantly decreased cardiac mortality in diabetic patients. However, increased risks for cardiovascular disease still exist in insulin resistant and diabetic patients, which are more specifically related to vascular cell dysfunctions induced by insulin resistance or deficiency. Our laboratory has been characterizing the various effects of insulin directly on the cardiac and vascular wall. We have documented that cells from the cardiovascular system can respond to insulin both at the cell signaling and functional levels. Insulin s effects on the vasculature include the regulation of endothelial nitric oxide synthase (enos) and vascular endothelial growth factor (VEGF) expression and activation. Insulin also has mitogenic actions on the vascular cells, such as the expressions of endothelin-1 (ET-1), PAI-1, regulation of extracellular matrix production and DNA synthesis. In general, insulin mediates its vascular actions on the vasculature via two major pathways. The metabolic actions of insulin are due to the activation of IRS-1/PI3K/Akt/PKC- pathways. Insulin s mitogenic actions are usually mediated by Raf/MAPK pathways. Thus, those actions of insulin mediated by IRS-1/PI3K/Akt pathway are usually rapid and antiatherogenic. In contrast, insulin s actions mediated by MAPK activation are associated with pro-atherogenic effects in insulin resistant or diabetic states. Deficiencies of insulin s actions in diabetes can be due to the destruction of the islets due to the autoimmune process or metabolic stress. Insulin s actions on the vascular wall could also be inhibited by inflammatory factors, oxidants and other processes. All these factors will cause the selective inhibition of insulin s signaling through the PI3K/Akt pathway while enhancing the actions mediated by MAPK cascade. We have shown that the loss of insulin s actions through the PI3K/Akt pathway selectively is responsible for endothelial dysfunction, decreases in capillary density or poor collateral vascular formation in the myocardium, and increases in atherogenesis via the loss of enos and other anti-oxidative stress enzymes in the cardiovascular tissues. The mechanism for the selective vascular insulin resistance appears to be the effect of metabolic abnormalities induced by diabetes, such as oxidized LDLs, activation of PKC and other stress kinases, all of which can selectively inhibit IRS- 1/PI3K/Akt pathway while enhancing the MAPK cascade. We will present multiple studies using animal models of atherosclerosis and endothelial dysfunction to demonstrate the role of selective vascular insulin resistance in inducing cardiovascular pathologies in diabetes and insulin resistant states. 51