Endothelial dysfunction in type 2 diabetes
Cardiovascular disease (CVD) is by far the most common complication of type 2 diabetes. Suffering from type 2 diabetes does not only significantly increase the risk of CVD but is also associated with poor survival, both acutely and in the long term, after a myocardial infarction (MI). In fact, total mortality from coronary artery disease (CAD) in subjects with type 2 diabetes without a previous MI is as high as that of non-diabetic individuals with a previous infarction. Regardless of the risk factors are involved, atherosclerosis is an inflammatory disease in which endothelial dysfunction plays an essential role at all stages of the atherosclerotic process. Endothelial dysfunction is commonly observed in association with type 2 diabetes and other situations characterized by insulin resistance, and are related to the risk for initial or recurrent cardiovascular malfunction. In states of insulin resistance; hyperglycemia, dyslipidemia, obesity, hypertension and low-grade inflammation all affect the endothelial function negatively, in a multifaceted and complex manner. Many different alterations in lifestyle and pharmacological interventions designed to improve endothelial function may also lower CVD risk. Besides the documented insulinotropic effects of glucagon-like peptide-1 (GLP-1) mimetics, their effects on the cardiovascular function is of high interest. GLP-1 receptors are expressed in the vasculature and heart. Recent studies have demonstrated that GLP-1 mimetics have wide-ranging cardiovascular actions such as improvement of endothelial dysfunction and left ventricular ejection fraction in subjects with CAD. The physiological and potential pharmacological role of GLP-1 and its analogues will be discussed in this context.