The cornerstone of DM therapy is optimal glycemic control, because hyperglycemia is the basis of all the metabolic disturbances that occurs in the disease. As shown previously, both in vivo and in vitro elevated glucose levels have been shown to cause abnormal endothelium-dependent relaxation. Lower glucose levels also result in a decrease in insulin levels, which consequently may also improve endothelial function. Therefore, therapy should be directed toward lowering glucose levels and increasing insulin sensitivity.
The effect of oral hypoglycemic agents on endothelial function is controversial and probably relates to the agent and model of diabetes being evaluated. Metformin has been shown to improve endothelium-dependent function in the mesenteric arteries of insulin-resistant rats in vitro (165), and the ATP-dependent potassium channel blocker gliclazide ameliorated endothelium-dependent relaxation of the aortas of (alloxan-induced) diabetic rabbits (166). However, clinical studies evaluating the effect of oral hypoglycemics on endothelial function have shown either no difference (167) or diminished reactivity to acetylcholine once the agent is discontinued (120).
Recent work has demonstrated that one of the thiazolidinediones, (a group of insulin-sensitizing agents), rosiglitazone, improved endothelial function and insulin resistance for patients with type 2 diabetic subjects, suggesting that therapy for insulin resistance may improve endothelial dysfunction (168).
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