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

ObjectiveTo investigate the effect of pioglitazone on endothelial and adipose tissue dysfunction in newly detected IGT patients with CAD.Methods and designParticipants (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 hyperinsulinemic clamp).ResultsNo 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 μg/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 ± 2.0 mg kg−1 min−1, p < 0.05).A multiple regression analysis indicated that increasing of HMW-Ad after pioglitazone predicted increased FMD.ConclusionPioglitazone significantly improves endothelial and adipose tissue dysfunction in pre-diabetic patients with CAD.