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High Prevalence of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women With Gestational Diabetes Mellitus or Type 1 Diabetes

The role of intrauterine hyperglycemia

¹ Department of Obstetrics, Copenhagen Center for Pregnant Women with Diabetes, Copenhagen University Hospital, Rigshospitalet, Denmark
² Department of Endocrinology, Copenhagen University Hospital, Rigshospitalet, Denmark
³ Steno Diabetes Center, Copenhagen, Denmark
⁴ Department of Endocrinology, Odense University Hospital, Odense, Denmark

Address correspondence and reprint requests to Tine Dalsgaard Clausen, MD, Department of Obstetrics 4031, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail: tine.dalsgaard.clausen{at}dadlnet.dk

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 mellitus (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-h 75-g oral glucose tolerance test (OGTT) was evaluated in 597 subjects, 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-type 1), 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 (ORs) 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-type 1 compared with O-BP. In O-type 1, 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.

Abbreviations: GAD65ab, GAD65 autoantibody • GDM, gestational diabetes mellitus • LGA, large for gestational age • OGTT, oral glucose tolerance test • SGA, small for gestational age

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