Effects of pioglitazone on endothelial function, insulin sensitivity, and glucose control in subjects with coronary artery disease and new-onset type 2 diabetes.

OBJECTIVE: About one of five patients with coronary artery disease (CAD) suffers from previously unknown, predominantly postprandial type 2 diabetes. In the process of atherogenesis and the subsequent increased cardiovascular mortality of diabetic patients, endothelial dysfunction is suspected to play an important role, and it is observed in diabetic as well as insulin-resistant states. Thus, the aim of our study was to investigate the effect of pioglitazone on endothelial dysfunction, insulin sensitivity, and glucose control in newly detected type 2 diabetic patients with CAD.

RESEARCH DESIGN AND METHODS: We investigated 42 patients (39 men and 3 women, age 60.25 +/- 7.5 years, HbA1c 6.1 +/- 0.5%) with manifest CAD and newly detected type 2 diabetes. A randomized, double-blind, placebo-controlled, parallel study with pioglitazone (30 mg/day for 12 weeks) was performed. At study entry and end, we performed an oral glucose tolerance test and measurements of endothelial dysfunction by photoplethysmographic pulse wave analysis.

RESULTS: Endothelial dysfunction was severely impaired at baseline in both groups. After 12 weeks, endothelial dysfunction was significantly better in the pioglitazone group (change of reflection index 6.5 +/- 5.1 vs. 1.6 +/- 2.9%, P = 0.002) compared with placebo. Insulin sensitivity, as assessed by homeostasis model assessment (2.20 +/- 1.62 vs. 3.61 +/- 1.87, P = 0.01), or the change of insulin sensitivity index from baseline to study end (0.021 +/- 0.023 vs. -0.003 +/- 0.012 micromol x kg(-1) x min(-1) per pmol/l, P = 0.0001) and beta-cell function (57.42 +/- 49.86 vs. 21.78 +/- 18.54 mU/l per mmol/l, P = 0.0014) significantly improved in the pioglitazone group, with no change observed after placebo.

CONCLUSIONS: Pioglitazone improves endothelial dysfunction independently from the observed benefits on insulin sensitivity and beta-cell function in patients with newly diagnosed type 2 diabetes and CAD.