Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitazone on endothelial function in patients with diabetes.

摘要

The vascular endothelium has emerged as a critical determinant of cardiovascular health and disease, and improving endothelial function is an important target for therapy. Accumulating evidence suggests that insulin resistance in patients with diabetes and the metabolic syndrome may impair endothelial function, uncovering a proinflammatory, proatherosclerotic vascular phenotype. The rationale and design of the Glitazones and the Endothelium (GATE) study is presented. The GATE study is a randomized, double-blind study for the evaluation of the effects of rosiglitazone versus placebo on endothelial function when used as an add-on therapy in patients with diabetes currently treated with oral therapy. It is hypothesized that the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone will improve endothelium-dependent vasodilation, and that this effect will be related to improvements in insulin sensitivity, with concomitant reductions in whole-body insulin resistance. Furthermore, the beneficial effects of rosiglitazone will be additive to those of existing oral therapies that may modulate endothelial function. Because endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis, the GATE study may provide the rationale and impetus for the aggressive treatment of insulin-resistant patients with glitazone therapy.