The investigators have shown that 50% of Latino women with gestational diabetes mellitus (GDM) develop type 2 diabetes within 5 years after the index pregnancy. The overall goal of their research program is to develop strategies for prevention of diabetes in these high-risk women. Their primary hypothesis is that the subset of Latino women with GDM who are at highest risk for diabetes have a defect that limits pancreatic B-cell compensation for insulin resistance. That hypothesis predicts that (a) poor B-cell function in late pregnancy, when all women are insulin resistant, will identify women at high risk for diabetes after pregnancy, and (b) that insulin resistance following pregnancy will increase the risk of diabetes in women with a B-cell defect. In the initial 5 years of the project, the investigators performed detailed assessments of B-cell function, insulin sensitivity, and body composition in 150 Latino women with GDM during the third trimester of pregnancy. They repeated the tests at 15 months postpartum and will complete testing at 30 months postpartum during the current cycle. Results to date indicate that, in the third trimester, women with GDM have (in addition to hyperglycemia) peripheral and hepatic insulin resistance, elevated basal glucose production, and reduced insulin responses to glucose compared to normal pregnant women. Moreover, poor B-cell function, post-challenge hyperglycemia and elevated basal glucose production were predictive of diabetes within 15 months postpartum. The investigators project that they will have a statistically meaningful sample of women in follow-up until at least 90 months postpartum. Thus, for the next grant cycle, they propose to continue follow-up with detailed metabolic testing at 15-month intervals to: (a) identify antepartum characteristics that best predict the development of diabetes or protection therefrom during prolonged follow-up; and (b) identify characteristics outside of pregnancy that predict or attend the progression to diabetes. The former effort will test their prediction about the importance and nature of a B-cell defect early in the pathogenesis of diabetes. The latter effort will test their prediction that chronic insulin resistance will increase the risk of diabetes in women with such a B-cell defect. The investigators point out that the results could provide truly novel information about the pathogenesis of type 2 diabetes in very high risk women, thereby allowing identification of potential targets for interventions to delay or prevent diabetes and its long term complications.
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