Abstract

Objective: The role of intrauterine hyperglycemia and future risk of type 2 diabetes in human offspring is debated. We studied glucose tolerance in adult offspring of women with either gestational diabetes (GDM) or type 1 diabetes, taking the impact of both intrauterine hyperglycemia and genetic predisposition to type 2 diabetes into account.

Research Design and Methods: The glucose tolerance status following a 2-hour 75-g oral glucose tolerance test (OGTT) was evaluated in 597 primarily Caucasians aged 18-27 years. They were subdivided into four groups according to maternal glucose metabolism during pregnancy and genetic predisposition to type 2 diabetes: 1) offspring of women with diet-treated GDM (O-GDM), 2) offspring of genetically predisposed women with a normal OGTT (O-NoGDM), 3) offspring of women with type 1 diabetes (O-Type1) and 4) offspring of women from the background population (O-BP).

Results: The prevalence of type 2 diabetes and pre-diabetes (impaired glucose tolerance or impaired fasting glucose) in the four groups was 21%, 12%, 11% and 4% respectively. In multiple logistic regression analysis, the adjusted odds ratios (OR) for type 2 diabetes/pre-diabetes were 7.76 (95% CI 2.58-23.39) in O-GDM and 4.02 (1.31-12.33) in O-Type1 compared to O-BP. In O-Type1 the risk of type 2 diabetes/pre-diabetes was significantly associated with elevated maternal blood glucose in late pregnancy: OR 1.41 (1.04-1.91) per mmol/l.

Conclusions: A hyperglycemic intrauterine environment appears to be involved in the pathogenesis of type 2 diabetes/pre-diabetes in adult offspring of primarily Caucasian women with either diet-treated GDM or type 1 diabetes during pregnancy.