Insulin Resistance, Inflammation and Atherosclerosis

Type 2 diabetes and obesity are major risk factors for the development of coronary artery disease (CAD), and premature atherosclerosis. Both conditions are associated with insulin resistance, oxidative stress, and inflammation. Several factors that increase the risk of cardiovascular disease tend to cluster together in the same individual. Insulin resistance is believed to be a pathophysiological disturbance that underlies many of risk factors. Whether insulin resistance per se is a cardiovascular risk factor, is uncertain. Besides insulin resistance of myocardial muscle both in patients with type 2 diabetes and in non diabetic subjects with angiographically proven CAD, then is also a mismatch between the redistribution of blood flow and glucose uptake during insulization in diabetic patients. Also, the endothelial dysfunction and the hyperinsulinemia that accompany insulin resistance may adversely affect myocardial function. In metabolic tissues, insulin signaling via the phosphatidylinositol 3-kinase pathway (predominant in the metabolic tissues) leads to glucose uptake and is down-regulated. The other pathways of insulin-receptor signaling being a growthfactor like pathway (mediated by MAPk) is upregulated and its continued activity leads to atherosclerosis. This review will focus on the relationship between insulin resistance, inflammation and atherosclerosis in patients with type 2 diabetes and metabolic syndrome. It will also address the metabolic consequences of the insulin resistance syndrome and the impact of insulin resistance on process of atherosclerosis including insulin signaling in cells of the vasculature.