title: Incretin and glucagon levels in adult offspring exposed to maternal diabetes in pregnancy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Pregnant Women with Diabetes (L.K., T.D.C., E.R.M., P.D.) and Departments of Obstetrics (L.K., P.D.) and Endocrinology (E.R.M.), Rigshospitalet, DK-2100 Copenhagen, Denmark; Department of Gynaecology and Obstetrics (T.D.C.), Nordsjaellands Hospital, 3400 Hillerød, Denmark; Institute of Clinical Medicine (E.R.M., P.D.), Faculty of Health Science, University of Copenhagen, 2200 Copenhagen, Denmark; Novo Nordisk Foundation (NNF) Center for Basic Metabolic Research (T.H.), Section of Metabolic Genetics, University of Copenhagen, 2200 Copenhagen, Denmark; Faculty of Health Sciences (T.H.), University of Southern Denmark, 5230 Odense M, Denmark; and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Kelstrup
authors.forename: Tine D
authors.initials: TD
authors.lastname: Clausen
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
mesh_terms: D000293:Adolescent; D000328:Adult; D032721:Adult Children; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood*; D055815:Young Adult
chemical_list: D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon