Our study suggests that GDM and T2D share a similar genetic background. Our findings also provide further evidence that risk variants of MTNR1B are associated with GDM by increasing fasting plasma glucose and decreasing insulin secretion.

BackgroundGestational diabetes (GDM) has been associated with an elevated risk of type 2 diabetes in women after the pregnancy. Recognition of the factors differentiating the women at highest risk of progression to overt disease from those who remain normoglycemic after gestational diabetes is of key importance for targeted prevention programmes. To this aim, we investigated the incidence and risk factors of prediabetes and type 2 diabetes with a view to the underlying pathophysiological mechanisms in a long-term follow-up of women with a history of gestational diabetes.Methods489 women with GDM and 385 normoglycemic controls attended a follow-up study after pregnancy (mean follow-up time 7.3, SD 5.1 years) in Kuopio, Finland. Glucose tolerance was evaluated with an oral glucose tolerance test, insulin sensitivity by Matsuda insulin sensitivity index (ISI), and insulin secretion by Disposition Index 30 (DI30).ResultsGDM increased risk of pre-diabetes and diabetes (HR 3.7, 95% C.I. 2.8-4.7 and HR 40.7, 95% C.I. 5.3-310.1, respectively, after adjustment for confounding factors) and was associated with both increased fasting (P < 0.001) and 2-hour plasma glucose (P < 0.001) during OGTT at the follow-up study. This effect was attenuated when adjusted for Matsuda ISI but abolished after adjustments with DI30 suggesting insulin secretion is the key defect leading to type 2 diabetes after GDM pregnancy. Increase in waist circumference and weight after pregnancy predicted the development of hyperglycemic conditions in women with a history of GDM (P < 0.001, and P = 0.002, respectively).ConclusionsPre-diabetic stages after GDM pregnancy are frequent and reflect the progressive risk of type 2 diabetes in long-term follow-up. Hyperglycemia after GDM pregnancy results from beta cell failure and inability to compensate the increased insulin resistance by insulin secretion. Importantly, increase in waist circumference and as well as weight gain during the follow-up is associated with progression to prediabetes and type 2 diabetes in women with a history GDM.

The aim of this study was to evaluate the incidence of metabolic syndrome (MetS) during long-term follow-up of women with gestational diabetes (GDM). Furthermore, we evaluated the glycemic measures from an oral glucose tolerance test (OGTT) during pregnancy as predictors of incident MetS. Women diagnosed with GDM were divided into two groups according to the results of OGTT: one abnormal value = GDM1 (n = 338) and two abnormal values = GDM2 (n = 151), while women with normal glucose tolerance (n = 385) served as controls. MetS and its components were evaluated in a follow-up study (mean follow-up time 7.3 ± 5.1 years) according to the International Diabetes Federation (IDF) criteria. Fasting plasma glucose in OGTT was the best predictor of incident MetS in ROC (area under the curve) analysis. The incidence of MetS during a <5-year follow-up was 22.2% in controls, 39.3% in GDM1 and 60.4% in GDM2; and >10-year follow-up 24.2%, 46.2% and 62.5%, respectively. In controls and GDM2, the incidence of MetS remained nearly constant during the follow-up, whereas in GDM1 it increased. In conclusion, already mild gestational glucose intolerance may progress to MetS and therefore merits intervention measures to prevent future cardiovascular disease.