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.

The Diabetes Risk Phenotype of Young Women With Recent Gestational Diabetes

“…It was associated with several other components of the metabolic syndrome. This is in line with previous work from another group (32) and has implications for T2D prediction and preventive measures in women after GDM.…”

Effects of treatment with metformin and/or sitagliptin on beta‐cell function and insulin resistance in prediabetic women with previous gestational diabetes

“…This finding is in agreement with a recent meta‐analysis showing that despite modest benefits on glucose homeostasis in prediabetic individuals, there was no definitive evidence that DPP‐4 inhibitors could diminish the risk of type 2 diabetes in high‐risk individuals, including women with prior GDM . Therefore, our results underline the need for a more pathophysiologically driven approach targeting beta‐cell function and insulin sensitivity simultaneously to increase the probability of reducing the risk of developing type 2 diabetes, much in line with research showing that beta‐cell dysfunction may not be sufficient to account for progression to overt type 2 diabetes after pregnancy, although it remained the main driver of progression to overt type 2 diabetes after pregnancy . Former gestational diabetic women have lower insulin sensitivity compared with women remaining normotolerant during pregnancy.…”

Effects of antidiabetic agents on pancreatic beta-cell function in gestational diabetes: is there enough evidence?

“…Indeed, recent investigations showed that both insulin resistance and beta-cell function impairment may contribute to the development of type 2 diabetes in women with history of GDM. [1][2][3][4] The study by Tura et al [1] suggested that the critical event for the onset of type 2 diabetes was a marked deterioration of insulin sensitivity, but also beta-cell function showed a progressive decline in the women developing the disease; in fact, in the progressors, beta-cell function impairment was found as significant predictor of the subsequent disease development.…”