Editorial |
From the Department of Medicine, University of California at San Diego, La Jolla.
Correspondence to Dr Christopher Glass, Department of Medicine, Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0651.
Treatment of type 2 diabetes mellitus (DM) is directed at relieving symptoms of hyperglycemia and reducing the incidence of diabetes-associated pathologies. Complications of atherosclerosis, including myocardial infarction and stroke, are the most common causes of death in diabetic patients. Thiazolidinediones (TZDs) represent a relatively recent addition to the arsenal of pharmaceutical options for diabetes treatment. These agents are potent insulin sensitizers and significantly improve glycemic control in the majority of diabetic patients.1 Troglitazone, the first TZD to be marketed, has been replaced in clinical practice by the more potent TZDs, rosiglitazone and pioglitazone. There are now upwards of a million diabetic patients taking these agents in the United States, and the rising incidence of obesity and type 2 DM predicts an ever-growing patient population of patients who will be candidates for treatment with insulin sensitizers.
Given their antidiabetic actions, TZDs would be
expected to reduce atherosclerotic complications. Although there are a
few hints from small clinical studies that this may be the case, TZDs
have not been in clinical use for sufficient time to establish their
long-term effects on the development and clinical consequences of
atherosclerosis in diabetic patients. In 1995,
troglitazone was found to be a high-affinity ligand for the peroxisome
proliferatoractivated receptor-
(PPAR-
).2 There is now
extensive evidence that the TZD class of molecules exerts its
insulin-sensitizing effects through this
receptor.3 PPAR-
is a
ligand-activated transcription factor that is related to
receptors for steroid and thyroid hormones. In addition to regulating
glucose homeostasis, it has been shown
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