Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents

Patients with type 2 diabetes mellitus (T2DM) 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 CV 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 CV risk in patients with T2DM. Accordingly, CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of the insulin-sensitizing agents and of other antihyperglycemic medications on CV outcomes are discussed.