Pioglitazone improves endothelial and adipose tissue dysfunction in pre-diabetic CAD subjects

Objective: To investigate the effect of pioglitazone on endothelial and adipose tissue dysfunction in newly detected IGT patients with CAD. Methods and design: Participants (n = 25) were randomized to treatment with either placebo or pioglitazone (30 mg/day) for 12 weeks. Before and after treatment we evaluated endothelial function (flow-mediated dilation - FMD - of the brachial artery), circulating adipose and inflammatory markers (adiponectin isoforms, TNF-alpha, and high sensitivity-CRP), and insulin sensitivity (euglycemic hyper-insulinemic clamp). Results: No significant changes were observed in subjects (n = 12) treated with placebo. By contrast, subjects (n = 13) treated with pioglitazone had significant improvement in FMD (10.8 +/- 5.3 vs 13.3 +/- 3.6%, p < 0.01), accompanied by increased high molecular weight adiponectin (HMW-Ad) (1.7 +/- 1.2 vs 4.8 +/- 3.6 mu g/ml, p < 0.05) and decreased TNF-alpha (4.3 +/- 1.9 vs 3.2 +/- 1.2 pg/ml, p < 0.05) associated to an increased glucose disposal (4.8 +/- 1.9 vs 5.4 +/- 2.0mg kg(-1) min(-1), p < 0.05). A multiple regression analysis indicated that increasing of HMW-Ad after pioglitazone predicted increased FMD. Conclusion: Pioglitazone significantly improves endothelial and adipose tissue dysfunction in pre-diabetic patients with CAD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.