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

Abstract

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. 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. 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. 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.