Effect of Pioglitazone on Pancreatic -Cell Function and Diabetes Risk in Hispanic Women With Prior Gestational Diabetes
Anny H. Xiang,1 Ruth K. Peters,1 Siri L. Kjos,2 Aura Marroquin,3 Jose Goico,3 Cesar Ochoa,3 Miwa Kawakubo,1 and Thomas A. Buchanan2,3
The Pioglitazone In Prevention Of Diabetes (PIPOD) study was conducted to evaluate -cell function, insulin resistance, andthe incidence of diabetes during treatment with pioglitazone in Hispanic women with prior gestational diabetes who had completed participation in the Troglitazone In Prevention Of Diabetes (TRIPOD) study. Women who completed the TRIPOD study were offered participation in the PIPOD study for a planned 3 years of drug treatment and 6 months of postdrug washout. Oral glucose tolerance tests wereperformed annually on pioglitazone and at the end of the postdrug washout. Intravenous glucose tolerance tests (IVGTTs) for assessment of insulin sensitivity and -cell function were conducted at baseline, after 1 year on pioglitazone, and at the end of the postdrug washout. Of 95 women who were not diabetic at the end of the TRIPOD study, 89 enrolled in the PIPOD study, 86 completed at least onefollow-up visit, and 65 completed all study visits, including the postdrug tests. Comparison of changes in -cell compensation for insulin resistance across the TRIPOD and PIPOD studies revealed that pioglitazone stopped the decline in -cell function that occurred during placebo treatment in the TRIPOD study and maintained the stability of -cell function that had occurred during troglitazone treatmentin the TRIPOD study. The risk of diabetes, which occurred at an average rate of 4.6% per year, was lowest in women with the largest reduction in total IVGTT insulin area after 1 year of treatment. The similarity of ﬁndings between the PIPOD and TRIPOD studies support a class effect of thiazolidinedione drugs to enhance insulin sensitivity, reduce insulin secretory demands, and preserve pancreatic-cell function, all in association with a relatively low rate of type 2 diabetes, in Hispanic women with prior gestational diabetes. Diabetes 55:517–522, 2006
ype 2 diabetes frequently results from progressive failure of pancreatic -cells in a setting of chronic insulin resistance (1– 6). In the Troglitazone In Prevention Of Diabetes (TRIPOD) study (7), we found that treatment of insulinresistance with the thiazolidinedione drug, troglitazone, improved insulin sensitivity and reduced the incidence of type 2 diabetes in Hispanic women with prior gestational diabetes. Protection from diabetes was closely related to the degree to which endogenous insulin requirements were reduced soon after initiation of troglitazone treatment. Moreover, women who were protected from diabetes duringtroglitazone treatment had stable -cell function and insulin resistance for nearly 5 years. These ﬁndings provided evidence that reducing the secretory demands that are placed in pancreatic -cells by chronic insulin resistance can preserve -cell function and slow or stop progression to type 2 diabetes. Troglitazone was withdrawn from clinical use in 2000. The Pioglitazone In Prevention Of Diabetes(PIPOD) study was conducted to assess the effect of a currently available thiazolidinedione drug, pioglitazone, on pancreatic -cell function and, secondarily, insulin resistance and diabetes rates in women who completed the TRIPOD study.
RESEARCH DESIGN AND METHODS
The PIPOD study was an open-label observational study to determine the effects of pioglitazone in women with prior gestationaldiabetes who had completed the TRIPOD study. The details of the TRIPOD study have been previously published (7,8). Brieﬂy, Hispanic women of Mexican, Guatemalan, or Salvadoran descent with a recent history of gestational diabetes were randomized to 400 mg/day troglitazone or placebo between August 1995 and May 1998. Fasting glucose was measured at 3-month intervals, and oral glucose tolerance tests...