Overweight and the Metabolic Syndrome in Adult Offspring of Women with Diet-Treated Gestational Diabetes Mellitus or Type 1 Diabetes

Context: In animal studies, exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms. Human long-term follow-up studies on the same topic are few. Objective: The aim was to study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal hyperglycemia and outcome in the offspring. Design and Setting: We conducted a follow-up study of 1066 primarily Caucasian women aged 18-27 yr in the Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark. Participants: Offspring of women with diet-treated GDM (n = 168) and an unexposed reference group (n = 141) participated, as well as offspring of women with type 1 diabetes (n = 160) and offspring from the background population representing an unexposed reference group (n = 128). The follow-up rate was 56% (597 of 1066). Main Outcome Measures: Women with body mass index of at least 25 kg/m(2) were considered overweight. The metabolic syndrome was determined by the International Diabetes Federation 2006 criteria. Results: The risk of overweight was doubled in offspring of women with diet-treated GDM or type 1 diabetes compared with offspring from the background population, whereas the risk of the metabolic syndrome was 4- and 2.5-fold increased, respectively. Offspring risk of the metabolic syndrome increased significantly with increasing maternal fasting blood glucose as well as 2-h blood glucose (during oral glucose tolerance test). Conclusions: Adult offspring of women with diet-treated GDM or type 1 diabetes are risk groups for overweight and the metabolic syndrome. Intrauterine hyperglycemia may in addition to genetics and other factors contribute to the pathogenesis of overweight and the metabolic syndrome. (J Clin Endocrinol Metab 94: 2464-2470, 2009)