Is Insulin Resistance a Feature of or a Primary Risk Factor for Cardiovascular Disease?

The two major pathophysiological abnormalities in type 2 diabetes are insulin resistance and impaired insulin secretion. Insulin resistance is a general term meaning that insulin does not exert its normal effects in insulin-sensitive target tissues, such as skeletal muscle, adipose tissue, and liver, the major target tissues for insulin action in glucose metabolism. Insulin resistance (IR) promotes cardiovascular disease via multiple mechanisms, including changes in classic cardiovascular risk factors and downregulation of the insulin signaling pathways in different tissues. This review presents evidence for the association of insulin resistance with cardiovascular disease from clinical and population-based studies. The causality of the association of insulin resistance with cardiovascular disease is discussed on the basis of recent findings from the Mendelian randomization studies.