Thiazolidinediones

  1. Zachary T. Bloomgarden, MD
  1. Zachary T. Bloomgarden, MD, is a practicing endocrinologist in New York, New York, and is affiliated with the Diabetes Center, Mount Sinai School of Medicine, New York, New York

    This is the fifth in a series of articles on presentations at the American Diabetes Association Annual Meeting, Orlando, Florida, 4–8 June 2004.

    At a debate at the American Diabetes Association (ADA) meeting on the use of thiazolidinediones (TZDs) in type 2 diabetes, David M. Kendall (Minneapolis, MN) discussed their advantages. He presented evidence that the agents improve glycemic control, target the metabolic defects of insulin resistance and insulin deficiency, and potentially preserve β-cell function and, therefore, prevent diabetes. Furthermore, he discussed the role of insulin resistance in increasing cardiovascular disease (CVD) risk, the safety and tolerability of the drugs, and aspects of their cost.

    All oral hypoglycemic agents lower plasma glucose by 30–80 mg/dl and HbA1c by up to 2–2.5%. However, Kendall stated, only 25–30% of patients achieve adequate glycemic control with metformin or secretagogue monotherapy and only 15–20% with TZDs. “It is how we get there that is important,” he stated, and because hyperglycemia is caused by paired defects of both insulin resistance and deficiency, its treatment requires addressing both pathogenic defects. The U.K. Prospective Diabetes Study (UKPDS) showed that type 2 diabetes is a progressive disease with declining β-cell function but may have been flawed due to a lack of sufficiently high doses of insulin and not having TZDs or insulin analogs available. Kendall noted that the HbA1c goal for individuals with type 2 diabetes should be <7%, and perhaps should be <6%, although he noted that, on a population basis, glycemic treatment has not improved particularly over the past decade.

    Although insulin secretion is apparently increased in the setting of compensation to insulin resistance, subsequent progressive β-cell dysfunction occurs that is associated with adverse effects of hyperglycemia, insulin resistance, fatty acids, and adipocytokines. TZDs decrease insulin resistance and prevent the decline in β-cell mass, …

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