Effect of pioglitazone on insulin sensitivity, vascular function and cardiovascular inflammatory markers in insulin‐resistant non‐diabetic Asian Indians

AIMS: To determine the effects of pioglitazone (30 mg once daily for 16 weeks) on insulin sensitivity, insulin-mediated vasodilation, vascular inflammatory markers, fat distribution and lipids in Asian Indians and Caucasians of European ancestry. METHODS: Cross-sectional study. Eighteen non-diabetic Asian Indians and 17 Caucasians of comparable age (34 +/- 3 vs. 36 +/- 3 years) and body mass index (26.0 +/- 1.2 vs. 24.7 +/- 1.0 kg/m(2)) had measurements of insulin sensitivity (M, insulin clamp at 6 pmol/kg per min), abdominal fat (computed tomographic scan at L4-L5), endothelial-dependent (reactive hyperaemia, RH) and -independent (0.4 mg sublingual nitroglycerin, TNG) vasodilation using brachial artery ultrasound before and after the 2-h clamp at baseline and after pioglitazone therapy. RESULTS: Asian Indians were insulin resistant compared with Causasians during the baseline clamp (M = 25.6 +/- 1.7 vs. 41.1 +/- 2.2 micromol/kg per min, P < 0.0001) and improved significantly after pioglitazone (to 33.9 +/- 1.7 micromol/kg per min, P < 0.001). Vasodilatory responses to RH and TNG were similar in Asian Indians and Caucasians at baseline and did not change. Insulin-mediated vasodilation improved after pioglitazone in Asian Indians, but not in Caucasians, and correlated with the change in insulin sensitivity (r = 0.52, P = 0.03). C-reactive protein (CRP) was higher in Asian Indians vs. Caucasians (1.6 +/- 0.4 vs. 0.9 +/- 0.2 mg/l) and was negatively correlated with insulin sensitivity (r = -0.53, P = 0.02). In the Asian Indian group, CRP and plasminogen activator inhibitor-1 decreased and adiponectin increased after pioglitazone, but there were no significant changes in total or visceral fat. CONCLUSIONS: These results demonstrate that insulin-resistant Asian Indians respond favourably to an insulin sensitizer with improvements in insulin sensitivity, cardiovascular and inflammatory risk markers, and vascular responses to insulin. These agents may have a role in decreasing the risk of diabetes and cardiovascular disease in this high-risk population.