Insulin Resistance and Atherosclerosis: Implications for Insulin Sensitizing Agents.

Abstract

Type 2 diabetic patients are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained cardiovascular risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained cardiovascular risk in type 2 diabetic patients. Accordingly, cardiovascular outcome trials with pioglitazone have demonstrated that this insulin sensitizing thiazolidinedione reduces cardiovascular events in high risk type 2 diabetic patients. In this review the role of insulin resistance and the IRS in the development of atherosclerotic cardiovascular disease and the impact of the insulin sensitizing agents and of other antihyperglycemic medications on cardiovascular outcomes is discussed.