Effects of Diabetes and Insulin Resistance on Endothelial Functions

Cardiovascular (CV) complications are the primary cause of mortality and morbidity in patients with Type 1 (T1D) and Type 2 diabetes (T2D), which affect a variety of tissues and organs including the retina, myocardium, nerves, skin, and kidney. Insulin resistance and hyperglycemia are responsible for many abnormalities of vascular endothelial function in diabetes. These effects may be mediated via alterations in signal transduction pathways induced by advanced glycation end-products (AGE), reactive oxidative stress, and others. These, in turn, lead to selective impairment or enhancement of insulin signaling and affect both pro- and anti-atherogenic actions of insulin. Hyperinsulinemia, when present concomitantly with insulin resistance, may enhance insulin’s pro-atherogenic actions. Agents that can target the abnormalities of hyperglycemia-induced vascular dysfunction and improve insulin resistance in the endothelium can ultimately prevent the microvascular and CV complications of diabetes.