Randomized controlled trial using bosentan to enhance the impact of exercise training in subjects with type 2 diabetes mellitus

In type2 diabetes patients, endothelin (ET) receptor blockade may enhance blood flow responses to exercise training. The combination of exercise training and ET receptor blockade may represent a more potent stimulus than training alone to improve vascular function, physical fitness and glucose homeostasis. We assessed the effect of an 8week exercise training programme combined with either ET blockade or placebo on vasculature, fitness and glucose homeostasis in people with type2 diabetes. In a double-blind randomized controlled trial, brachial endothelium-dependent and -independent dilatation (using flow-mediated dilatation and glyceryl trinitrate, respectively), glucose homeostasis (using Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)) and physical fitness (maximal cycling test) were assessed in 18 men with type2 diabetes (60 +/- 6years old). Subjects underwent an 8week exercise training programme, with half of the subjects receiving ET receptor blockade (bosentan) and the other half a placebo, followed by reassessment of the tests above. Exercise training improved physical fitness to a similar extent in both groups, but we did not detect changes in vascular function in either group. This study suggests that there is no adaptation in brachial and femoral artery endothelial function after 8weeks of training in type2 diabetes patients. Endothelin receptor blockade combined with exercise training does not additionally alter conduit artery endothelial function or physical fitness in type2 diabetes.