title: Effect of a diabetic environment in utero on predisposition to type 2 diabetes.
abstract: BACKGROUND
  Type 2 diabetes is affected by genetics and environmental factors. We aimed to assess the effect of an in-utero diabetic environment independently of the genetic background for type 2 diabetes.
  
  
  METHODS
  We measured insulin sensitivity and insulin secretion in response to oral and intravenous glucose in 15 non-diabetic adult offspring of mothers with type 1 diabetes (exposed participants) and 16 offspring of type 1 diabetic fathers (controls). No participants had type 1 diabetes-associated autoantibodies. We also measured pancreatic polypeptide, a marker of parasympathetic drive to the pancreas.
  
  
  RESULTS
  There was no difference between the groups with respect to percent body fat and insulin sensitivity. Five of the 15 exposed participants, but none of the controls had impaired glucose tolerance (p=0.02). Early insulin secretion after an oral glucose tolerance test was lower in exposed participants than in controls: 8.6 IU/mmol (SD 5.4) in exposed participants with impaired glucose tolerance, 14.2 IU/mmol (6.5) in those with normal glucose tolerance and 17.7 IU/mmol (10.9) in controls (p=0.04). Mean insulin secretion rate during glucose infusion study was 4.7 pmol/kg per min (3.6) in people with impaired glucose tolerance, 5.5 pmol/kg per min (4.5) in exposed participants with normal glucose tolerance and 7.5 pmol/kg per min (6.1) in controls (p<0.0001). The area under the curve of pancreatic polypeptide 120 min after oral glucose ingestion was 1007 (429) in people with impaired glucose tolerance, 2829 (1701) in those with normal glucose tolerance, and 3224 (1352) in controls (p=0.04).
  
  
  CONCLUSIONS
  Exposure to a diabetic environment in utero is associated with increased occurrence of impaired glucose tolerance and a defective insulin secretory response in adult offspring, independent of genetic predisposition to type 2 diabetes. This insulin secretory defect could be related to low parasympathetic tone. Epidemiological studies are needed to confirm our observations before therapeutic strategies can be devised.
authors.affiliation: Department of Endocrinology and Diabetes, Saint-Louis Hospital, Assistance Publique, Hôpitaux de Paris, University of Paris VII-Medical School;, Paris, France
authors.forename: Eugène
authors.initials: E
authors.lastname: Sobngwi
authors.forename: Philippe
authors.initials: P
authors.lastname: Boudou
authors.forename: Franck
authors.initials: F
authors.lastname: Mauvais-Jarvis
authors.forename: Hervé
authors.initials: H
authors.lastname: Leblanc
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.forename: Patrick
authors.initials: P
authors.lastname: Vexiau
authors.forename: Raphaël
authors.initials: R
authors.lastname: Porcher
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Richard
authors.initials: R
authors.lastname: Pratley
authors.forename: P Antonio
authors.initials: PA
authors.lastname: Tataranni
authors.forename: Fabien
authors.initials: F
authors.lastname: Calvo
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gautier
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000196:embryology* / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D018149:Glucose Intolerance / Q000175:diagnosis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D010191:Pancreatic Polypeptide / Q000097:blood; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects
chemical_list: D007328:Insulin; D010191:Pancreatic Polypeptide