Detailed physiological characterization of the development of type 2 diabetes in Hispanic women with prior gestational diabetes mellitus

Abstract

Objective: To identify physiological and clinical variables associated with development of type 2 diabetes up to 12 years after pregnancies complicated by gestational diabetes.

Research design and methods: Seventy-two islet cell antibody-negative nondiabetic Hispanic women had oral (oGTT) and intravenous (ivGTT) glucose tolerance tests, glucose clamps, and body composition assessed between 15 and 30 months after pregnancies complicated by gestational diabetes mellitus (GDM). They returned for oGTTs at 15-month intervals until they dropped out, developed diabetes, or reached 12 years postpartum. Cox regression analysis was used to identify baseline predictors and changes during follow-up that were associated with development of type 2 diabetes.

Results: At baseline, relatively low insulin sensitivity, insulin response, and β-cell compensation for insulin resistance were independently associated with development of diabetes. During follow-up, weight and fat gain and rates of decline in β-cell compensation were significantly associated with diabetes, while additional pregnancy and use of progestin-only contraception were marginally associated with diabetes risk.

Conclusions: In Hispanic women, GDM represents detection of a chronic disease process characterized by falling β-cell compensation for chronic insulin resistance. Women who are farthest along at diagnosis and/or deteriorating most rapidly are most likely to develop type 2 diabetes within 12 years after the index pregnancy. Weight gain, additional pregnancy, and progestin-only contraception are potential modifiable factors that increase diabetes risk.

FIG. 1.

Kaplan-Meier plot of diabetes cumulative incidence rate in 72 women without diabetes at entry and with at least one follow-up oGTT. Vertical lines are 95% CIs. The numbers given by the Subjects line included subjects who developed diabetes and who were under follow-up without diabetes by the corresponding follow-up years.

FIG. 2.

A: Baseline disposition index and 95% CIs according to final diabetes status during the entire follow-up (left two bars) or within 5 years and >5 years after the index pregnancy (right two bars). B: Disposition index during follow-up in women who developed diabetes and in women who remained diabetes free. Data are plotted relative to end points of diabetes or final visit without diabetes. Numbers shown above/below the lines are the corresponding sample sizes. Log scale is depicted to reflect that data were log transformed prior to all data analysis; geometric means are presented.