Progression to type 2 diabetes in women with former gestational diabetes: time trajectories of metabolic parameters

Abstract

Aim of this study was analyzing the time trajectories of the metabolic parameters in European women with former gestational diabetes (fGDM), and determining predictors of type 2 diabetes onset. A group of seventy-six fGDM women were studied at the outpatient department of the University Clinic of Vienna. They were evaluated yearly with a 3 h-oral glucose tolerance test (OGTT) up to 7-years from delivery. At baseline, women also underwent an intravenous glucose tolerance test (IVGTT). Insulin sensitivity and beta-cell function were assessed by both OGTT and IVGTT. Women were divided into progressors (PROG) to diabetes (n = 19) and non-progressors (n = 57). Time trajectories of glycemia and other parameters were analyzed after synchronization to time of diabetes onset or last OGTT. Then, Cox proportional hazard regression analysis was performed to assess the predictive power of studied variables for diabetes onset. We found that, in PROG, time trajectories of glycemia were flat until diabetes onset, when they showed a marked increase (P<0.0001). Insulin sensitivity showed similar marked decrease (P<0.0001) at diabetes onset, together with a tendency to continuous slow decline in the previous years. At contrast, beta-cell function showed only continuous slow decline. Major predictors of diabetes onset were glycemic levels, BMI, insulin resistance, and condition of impaired glucose tolerance. In conclusion, in fGDM, marked deterioration of insulin sensitivity is associated with diabetes onset. Prevention strategies aimed at opposing to the insulin sensitivity derangement may be particularly beneficial.

Figure 1. Time trajectories of glycemic levels.

Fasting glucose (top), 2 h glucose (center) and mean glucose (bottom) in PROG (solid line) and NONPROG (dashed line). Data (mean±SE) are reported from year −5 to year 0 (time of diabetes onset for PROG, and of last examination for NONPROG). In PROG, the number of subjects at each time sample is: 6, 6, 9, 10, 13, 19 (from year −5 to year 0, respectively); in NONPROG: 45, 51, 48, 38, 25, 57, respectively.

Figure 2. Time trajectories of the main metabolic parameters.

OGIS (a), HOMA-R (b), beta-cell glucose sensitivity (c), insulin secretion at 5.5 mmol/l glucose level (d), fasting insulin secretion (e), total insulin secretion (f), rate sensitivity (g), and BMI (h), in PROG. Data (mean±SE) are reported from year −5 to year 0 (time of diabetes onset). The number of subjects at each time sample is: 6, 6, 9, 10, 13, 19 (from year −5 to year 0, respectively).

Figure 3. Kaplan-Meier plots of diabetes-free survival.

Plots refer to mean glucose (top), BMI (medium), insulin sensitivity (bottom). For each variable, subjects have been stratified for tertiles (low, medium, high). Numbers of subjects at risk in each stratum at each year have been reported. Log-rank χ² statistics was 13.3 (P = 0.001) for mean glucose, 10.7 (P = 0.005) for BMI, 12.6 (P = 0.002) for insulin sensitivity.