Endothelial Dysfunction in Diabetes: An Update on Mechanisms and Therapeutic Targets

Over recent years, the explosive increase in the worldwideprevalence of type 2 diabetes has transformed this disease into a major public health concern. Cardiovascular complications are the leading causes of morbidity in diabetic patients, whose cardiovascular mortality risk is up to four times higher than in non-diabetic subjects. Morphological and structural changes in large and small vessels are usually preceded by alterations in endothelial function, resulting from the unbalanced production of endothelial-derived vascular mediators. Metabolic disturbances including hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia all contribute to endothelial dysfunction via both distinct and overlapping mechanisms. In turn, abnormal synthesis and release of endothelial mediators may contribute to exacerbate the impaired function of metabolic tissues, thus creating a vicious circle where these conditions reciprocally reinforce and worsen each other. Increasing understanding on mechanisms underlying endothelial dysfunction in diabetes may serve to identify potential therapeutic targets, and help to develop novel therapeutic approaches for reducing cardiovascular risk rate in diabetic patients. This chapter summarizes the current knowledge on the most recently identified targets and therapies for the treatment of diabetes and its cardiovascular complications.