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Insulin Resistance and Vascular Dysfunction in Nondiabetic Asian Indians

Division of Endocrinology, Diabetes, and Metabolism (A.R., M.W., D.C.S.), Cardiovascular Division (M.D.G.-H.), and Department of Radiology (S.G.S.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; and Department of Radiology (V.R.), Department of Endocrinology, Diabetes, and Metabolism (C.S.M.), Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Annaswamy Raji, M.D., Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: araji{at}partners.org.

Asian Indians are at higher risk for diabetes and cardiovascular disease than European Caucasians. To examine the pathophysiology of this increased risk, we measured insulin sensitivity, cardiovascular risk factors, fat distribution, and endothelium-dependent (reactive hyperemia) and -independent (nitroglycerin) vasodilation before and after a 2-h hyperinsulinemic clamp (40 mU/m²·min) in 25 nondiabetic Asian Indians and 15 Caucasians with similar age and body mass index. Asian Indians had higher fasting insulin than Caucasians (6.7 ± 0.8 vs. 3.7 ± 0.3 µU/ml, P = 0.007) but similar FPG (90 ± 2 vs. 88 ± 2 mg/dl). Glucose uptake during the clamp was markedly reduced in Asian Indians vs. Caucasians (4.5 ± 0.3 vs. 7.5 ± 0.4 mg/kg·min, P < 0.0001). During the clamp, basal brachial artery diameter increased less in Asian Indians vs. Caucasians (2.6 ± 1.0 vs. 5.7 ± 1.0%, P = 0.04), and the reduction was correlated with the impairment in insulin sensitivity (r = 0.38, P = 0.04). In contrast, vasodilatory responses to reactive hyperemia and nitroglycerin were similar in Asian Indians and Caucasians both before and during hyperinsulinemia. Plasminogen activator inhibitor-1 and FFA were significantly elevated and adiponectin was significantly lower in Asian Indians vs. Caucasians, and there were trends toward higher low-density lipoprotein and triglycerides, lower high-density lipoprotein, and increased total, sc, and visceral fat. These risk factors were all significantly correlated with insulin sensitivity. Thus, apparently healthy Asian Indians have severe insulin resistance, dyslipidemia, elevated plasminogen activator inhibitor-1, impaired insulin-mediated vasodilation, and trends toward altered body fat distribution. These abnormalities may contribute to the increased risk of diabetes and cardiovascular disease in this population.

This work was supported, in part, by National Institutes of Health Grants K23 DK604662 (to A.R.) and M01 RR02635 (General Clinical Research Center at Brigham and Women’s Hospital) and a grant from Takeda Pharmaceuticals.

Abbreviations: BMI, Body mass index; CAD, coronary artery disease; CRP, C-reactive protein; DM, type 2 diabetes; FFA, free fatty acid(s); HDL, high-density lipoprotein; IAFMV, insulin-augmented flow-mediated vasodilation; ICAM, intercellular adhesion molecules; LDL, low-density lipoprotein; NS, not significant; OGTT, oral glucose tolerance test; PAI-1, plasminogen activator inhibitor-1; VCAM, vascular cellular adhesion molecules; WHR, waist to hip circumference ratio.

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