ABSTRACT
Type 2 diabetes is a burgeoning epidemic associated with substantial morbidity and mortality and afflicting more than 150 million people worldwide (1,2). Intensive control of blood glucose significantly reduces and ameliorates the microvascular complications of retinopathy, nephropathy, and neuropathy. However, up to 80% of patients with type 2 diabetes die from the macrovascular complications of cardiovascular disease. This increased incidence of accelerated atherosclerosis disease is closely associated with insulin resistance, which is a major pathophysiologic abnormality in type 2 diabetes and is known to be intricately involved in the development of not only hyperglycemia, but also dyslipidemia, hypertension, hypercoagulation, vasculopathy, and accelerated atherosclerotic cardiovascular disease. This cluster of metabolic abnormalities has been variously termed the insulin resistance or metabolic syndrome (3,4). The effects of thiazolidinediones, through their peroxisome proliferator-activated receptor g (PPAR-g) agonist, not only improve insulin sensitivity and glycemic control with reduced insulin requirements, but also have other potentially favorable effects on components of the insulin resistance or metabolic syndrome. These effects on lipid and adipose tissue metabolism and vascular endothelial function have the potential to modify pro-atherogenic metabolic processes and improve cardiovascular risk. A thiazolidine 2-4 dione structure is common to all thiazolidinediones, and they differ in their side chain, which alters their pharmacologic and side-effect profiles. Two compounds in this class are presently approved for use in the United States and around theworld-rosiglitazone and pioglitazone. The first agent in this class, troglitazone, waswithdrawn inMarch 2000, after reports of fulminant hepatotoxicity associated with its use. In clinical use so far, rosiglitazone and pioglitazone appear to be devoid of idiosyncratic, fulminant hepatotoxicity.
