Long-term changes in glucose metabolism after gestational diabetes: A double cohort study

Abstract

Background: Gestational 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. Methods: 489 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). Results: GDM 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). Conclusions: Pre-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.