Thiazolidinediones and Type 2 Diabetes: From Cellular Targets to Cardiovascular Benefit

The prevalence of type 2 diabetes is evolving globally at an alarming rate. This fact is mainly the result of our global lifestyle "modernization" that has resulted in overweight and obesity. Dysfunction of peroxisome proliferator activated receptor-gamma (PPAR-gamma) has been implicated in the development of insulin resistance, while a reduce expression of many PPAR-gamma regulated genes has been observed in an obese diabetic state. Thiazolidinediones (TZDs) are potent exogenous agonists of PPAR-gamma, which augment the effects of insulin to its cellular targets and mainly at the level of adipose tissue. Preclinical and clinical studies have demonstrated that apart from their glucose-lowering activity, these drugs also regulate the production of inflammatory mediators by cells that play a pivotal role in the pathogenesis of atherosclerosis. This paper summarizes the evolving changes observed in an enlarged adipose tissue and examines the activity of TZDs in their main cellular targets. It also discusses whether these cellular pleiotropic effects can result in a clinically meaningful outcome, in terms of cardiovascular benefit, in this population.