Metabolic Syndrome in Asians

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1 Metabolic Syndrome in Asians Alka Kanaya, MD Asst. Professor of Medicine, UCSF Asian CV Symposium, November 17, 2007 The Metabolic Syndrome Also known as: Syndrome X Insulin Resistance Syndrome The Deadly Quartet The Dysmetabolic syndrome Glucose Intolerance, Diabetes Obesity Dyslipidemia Hypertension Five Definitions WHO EGIR NCEP AACE IDF Glucose HDL TG BP Waist Other: Insulin Ualb Insulin Several NCEP criteria Fulfill 3 criteria: Waist: >102 (or 94) cm, >88 cm HDL: <40 men,<50 women (or meds) Triglycerides: 150 mg/dl (or meds) BP: 130/ 85 (or med use) Fasting glucose: 100 mg/dl (or meds) NCEP, Circ,

2 Pathophysiology Pathophysiology Insulin Resistance Fat Third Factor? Insulin Resistance Definition: Change in physiologic regulation, when a fixed dose of insulin causes less of an effect on glucose metabolism than occurs in normal individuals. Recognized since 1930 s Still don t know the exact mechanism Etiology of T2DM Bergman,

3 Adiposity Normal Glucose Tolerance Pre-diabetes Impaired Glucose Tolerance (IGT) Impaired Fasting Glucose (IFG) Type 2 Diabetes Fat Depots: Subcutaneous: 60-70% Intra-abdominal: 15-25% (or intraperitoneal) Retroperitoneal (5%) Intramuscular: 5-10% Linked with diabetes and atherosclerosis since 1940 s Fat Fat distribution Déspres, Quebec 3

4 Fat distribution Ethnic differences in fat dist. Asians and s are more prone to visceral obesity A.A. and s develop less visceral obesity A.A. have more subcutaneous fat stores than s Why is visceral fat so bad? What it secretes FFA Fat Cells Kopelmen, 2000 Hormones Leptin Cortisol Estradiol Lipoproteins LPL CETP Apo E PLTP Peptides Adiponectin PAI-1 Angiotensinogen Agouti Resistin Visfatin Complement Factors Adipsin C3 Adipose Tissue Cytokines TNFα IL-6 Growth Factors TGF-ß IGF-1 VEGF 4

5 Proposed Mechanism Proposed Mechanism Vascular Inflammation IL-6 & TNF-α IL-6 & TNF-α Dyslipidemia PAI-1 Adipose tissue FFA Reduced Thrombolysis PAI-1 Adipose tissue FFA Hypertension Resistin & Adiponectin Resistin & Adiponectin Insulin Resistance Rosenson, 2005 Rosenson, 2005 Reduced Thrombolysis Proposed Mechanism PAI-1 Vascular Inflammation IL-6 & TNF-α Adipose tissue FFA Dyslipidemia Hypertension Metabolic syndrome and Atherosclerosis in South Asians Living in America (The MASALA study) Resistin & Adiponectin Insulin Resistance CVD Rosenson,

6 Conceptual Framework Obesity Inflammation Adiposity Insulin Resistance Metabolic Syndrome Thrombosis Atherosclerosis Clinical CVD MASALA Population-based Ages yrs N = 150 One site Cross-sectional Design MESA Population-based Ages yrs N = 6,500 6 sites (Columbia, Hopkins, NWU, Minnesota, UCLA, Wake Forest) Prospective cohort: exam 4 now Eligibility Criteria Inclusion: Age 45 to 84 years Self-identified as Asian Indian Exclusion: (same as MESA) Prior history of CHD, CVD, CHF, a. fib, angina, cardiac procedures or surgery, PM/defibrillator Active cancer treatment; <5 y life expectancy Weight >300 lbs; Impaired cognition Plans to move out of area in next 5 yrs; Nursing home resident or on waiting list 6

7 Clinical Measurements Demographic, lifestyle, dietary recalls Weight, height, waist, hip Seated BP ISI by 2-hour OGTT Basic chemistry, lipoproteins, inflammatory factors, adipocytokines Whole body DEXA Abdominal visceral & SQ fat (CT) MESA comparison Indian Age, y 57±8 61±10* 62±10* 61±9* 60±4* Not born in U.S. 98% 96% 7%* 9%* 68%* Educ HS 12% 41%* 21%* 30%* 46%* Income >$75K 65% 17%* 36%* 18%* 7%* * p<0.001 in comparison to Asian Indians MESA comparison Abdominal CT data Indian BMI 26 ± 5 24 ± 3* 28 ± 5* 30 ± 6* 29 ± 5* Waist 96 ± ± 10* 98 ± ± 15* 101 ± 13* Total body fat 35 ± * p<0.001 in comparison to Asian Indians 7

8 Body fat area comparisons HTN comparison Area, cm Indians Chinese s s s % * n = Fat Subcutaneous Fat 0 Indian Chinese * p<0.001 in comparison to Asian Indians Cholesterol comparisons Glucose Tolerance (mg/dl) Total Chol Indian 188±33 193±32 196±35 190±36 198±38 LDL 113±30 115±29 117±30 116±33 120±33* 29% 35% Normal PreDM T2DM HDL 49±14 49±13 52±16* 52±15* 47±13 36% TG 133±63 143±85 133±90 105±69 157±101 * p<0.05 in comparison to Asian Indians 8

9 Diabetes comparisons Indians DM* 24 15** 7** Pre-DM Normal *Defined by hypoglycemic med use or FPG 126 mg/dl Pre-DM: fasting glucose mg/dl ** p<0.05 compared to Asian Indians Indians Metabolic syndrome 39 26* 30* If waist >94 cm for men 44% * p<0.05 in comparison to Asian Indians Conclusions: South Asians Higher SES, low smoking and moderate alcohol use High diabetes prevalence, despite less overweight and comparable PA High prevalence of metabolic syndrome Higher prevalence of all metabolic risk factors than Chinese Searching for explanations 9

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