American Diabetes Association 60th Scientific Sessions, 2000: thiazolidinediones, obesity, and related topics.

Abstract

This is the second of four reports on the American Diabetes Association^M(ADA) 60th Scientific Sessions held in San Antonio, TX, in June 2000. It^Mcovers topics related to thiazolidinediones, insulin resistance, and^Mobesity. At a debate at the meeting, Thomas A. Buchanan, Los Angeles, CA, spoke in favor of the use of thiazolidinediones (TZDs) for prevention of diabetes. He described a prevention trial in a mainly Hispanic group of patients who had previously had gestational diabetes mellitus (GDM) at ∼30 years of age. Approximately 10% of such women have type 2 diabetes after pregnancy, and their ultimate diabetes risk approximates 50%. These women have decreased β-cell function and insulin resistance, both during and after pregnancy. Buchanan hypothesized that the β-cell defect is either caused or worsened by insulin resistance. In 1994, given the hyperbolic relationship between insulin secretion and insulin resistance, his group adopted the strategy of increasing insulin sensitivity with troglitazone. The initial short-term study was of women who had been diagnosed with GDM within the past 4 years and impaired glucose tolerance (IGT), whose risk of developing type 2 diabetes is ∼80%. Insulin sensitivity increased with treatment, and the insulin responses to oral and intravenous glucose and to intravenous tolbutamide, suggesting “afterload reduction for the β-cell.” Based on these data, the Troglitazone in Prevention of Diabetes (TRIPOD) study was started in a group of women who had had GDM and who had an estimated 70% 5-year risk of developing diabetes; 121 received placebo and 114 troglitazone (400 mg daily), with 27 and 29 months of follow-up. There was no significant difference in weight gain or pregnancy rates. Intention-to-treat analysis showed a 60% reduction in diabetes, with a 12.4% annual risk in patients receiving placebo and 5.7% annual risk in those treated with troglitazone. Buchanan noted that approximately one-third of the …