Previous studies have shown that Asian Indians (AIs) are insulin resistant and at high risk for developing diabetes and coronary heart disease, compared with Caucasians. To examine whether differences in body fat distribution contribute to this risk, 12 healthy AIs and 12 Caucasians matched for age and body mass index (BMI) underwent a 75-g oral glucose tolerance test, 2-h euglycemic hyperinsulinemic clamp, abdominal (L2-3) computed tomography scan, and fasting lipid and plasminogen activator inhibitor-1 (PAI-1) levels. Despite similar fasting plasma glucose levels, AIs exhibited fasting hyperinsulinemia (P = 0.001), higher glucose (P = 0.03) and insulin (P = 0.004) levels during the oral glucose tolerance test, and reduced glucose disposal rate (R(d)) (4.7 +/- 0.4 vs. 7.5 +/- 0.3 mg/kg per min, P < 0.0001) during the clamp. AIs had significantly lower high-density lipoprotein, higher low-density lipoprotein, and significantly higher PAI-1 levels (P = 0.01). Despite similar BMI, AIs had significantly greater total abdominal fat (P = 0.04) and visceral fat (P = 0.04). In all subjects, measures of fat mass were inversely correlated with R(d) during the clamp (r = -0.47 to -0.61, P < 0.01-0.001). Visceral fat mass was correlated with triglycerides, low-density lipoprotein, and high-density lipoprotein (P < 0.002-0.0001). PAI-1 was inversely correlated with R(d) in AIs (r = -0.70, P < 0.01) and not in Caucasians (r = -0.24, P = 0.44). For comparable BMI and age, healthy AIs have physiologic markers for insulin resistance, dyslipidemia, and increased cardiovascular risk, compared with Caucasians. Alterations in body fat distribution--particularly increased visceral fat--may contribute to these abnormalities.