Incretin and Glucagon Levels in Adult Offspring Exposed to Maternal Diabetes in Pregnancy

Context: Fetal exposure to maternal diabetes is associated with increased risk of type 2 diabetes mellitus (T2DM) later in life. The pathogenesis of T2DM involves dysfunction of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as hyperglucagonemia. Objective: Our aim was to investigate circulating plasma levels of GLP-1, GIP, and glucagon during the oral glucose tolerance test (OGTT) in adult offspring of women with diabetes in pregnancy. Design and Participants: We conducted a follow-up study of 567 offspring, aged 18-27 years. We included two groups exposed to maternal diabetes in utero: offspring of women with diet-treated gestational diabetes mellitus (O-GDM; n = 163) or type 1 diabetes (O-T1DM; n = 146). Two reference groups were included: offspring of women with risk factors for GDM, but normoglycemia during pregnancy (O-NoGDM; n = 133) and offspring from the background population (O-BP; n = 125). The subjects underwent a 75-g OGTT with venous samples at 0, 30, and 120 minutes. Results: Fasting plasma levels of GLP-1 were lower in the two diabetes-exposed groups compared to O-BP (O-GDM, P = .040; O-T1DM, P = .008). Increasing maternal blood glucose during OGTT in pregnancy was associated with reduced postprandial suppression of glucagon in the offspring. Lower levels of GLP-1 and higher levels of glucagon during the OGTT were present in offspring characterized by overweight or prediabetes/T2DM at follow-up, irrespective of exposure status. Conclusion: Lower levels of fasting GLP-1 and impaired glucagon suppression in adult offspring exposed to maternal diabetes during pregnancy are diabetogenic traits that may contribute to glucose intolerance in these persons, but further investigations are needed.