Atherosclerosis in type 2 diabetes mellitus and insulin resistance: mechanistic links and therapeutic targets

Abstract

The ongoing heavy burden of cardiovascular disease associated with diabetes mellitus highlights the failure of current treatment strategies to address effectively the cardiovascular risk profile in such patients. Insulin resistance is not only an underlying feature in most cases of type 2 diabetes, but is also associated, through the Insulin Resistance Syndrome, with cardiovascular risk factors that promote atherothrombosis through diverse mechanisms. Growing evidence suggests that treatment with anti-diabetic agents that improve insulin sensitivity, such as the thiazolidinediones, improve multiple components of the Insulin Resistance Syndrome, have beneficial effects on various atherothrombotic mechanisms, and reduce atherosclerosis in animal models and perhaps humans as well. Given data implicating chronic inflammation as a central feature of atherosclerosis, the anti-inflammatory activity of the thiazolidinediones may contribute to their potential anti-atherosclerotic effects. An improved understanding of the mechanisms linking diabetes, atherosclerosis, and cardiovascular disease is needed in order to understand how these and other current and emerging therapies might reduce diabetes-associated cardiovascular disease.