http://www.medscape.org/viewarticle/514729
Targeting Insulin Resistance: PPARs, Type 2 Diabetes, and Cardiovascular Risk

Introduction
Insulin resistance (IR) is widely recognized as a core physiologic defect contributing to the development of both type 2 diabetes and cardiovascular disease (CVD).The majority of individuals with type 2 diabetes are known to be insulin-resistant, and this IR, when coupled with an inadequate pancreatic beta-cell response, results in hyperglycemia.[1] Both clinical and epidemiologic data support the association between IR and an increase in CVD risk. IR is associated with the development of a cluster of characteristic CVD risk factors, including hypertension; an atherogenic dyslipidemia (characterized by low high-density lipoprotein cholesterol [HDL-C], increased triglycerides, and an increase in the prevalence of small, dense low-density lipoprotein [LDL] particles); and a proinflammatory, prothrombotic vascular environment, all of which likely contribute to the increase in CVD risk observed.

Given the accepted role of IR in the pathogenesis of diabetes and CVD, therapies that improve insulin action are used commonly for the management of hyperglycemia in diabetes. Moreover, there is significant interest in diabetes therapies that may limit CVD risk. Specifically, the impact of peroxisome proliferator activating receptor (PPAR)-gamma agonists, such as the thiazolidinediones (TZDs) on both diabetes control and CVD risk, has been widely discussed. These PPAR activators are well known to improve glucose control -- in great part by improving insulin action in the periphery -- and may improve a number of CVD risk factors, including hypertension, dyslipidemia, and the vascular, hemodynamic, and hemostatic abnormalities that are common in those with diabetes.