Consequences of fetal exposure to maternal diabetes in offspring

J Clin Endocrinol Metab. 2006 Oct;91(10):3718-24. doi: 10.1210/jc.2006-0624. Epub 2006 Jul 18.


Context: Type 2 diabetes is the result of both genetic and environmental factors. Fetal exposure to maternal diabetes is associated with a higher risk of abnormal glucose homeostasis in offspring beyond that attributable to genetic factors, and therefore, may participate in the excess of maternal transmission of type 2 diabetes.

Evidence acquisition: A MEDLINE search covered the period from 1960-2005.

Evidence synthesis: Human studies performed in children and adolescents suggest that offspring who had been exposed to maternal diabetes during fetal life exhibit higher prevalence of impaired glucose tolerance and markers of insulin resistance. Recent studies that directly measured insulin sensitivity and insulin secretion have shown an insulin secretory defect even in the absence of impaired glucose tolerance in adult offspring. In animal models, exposure to a hyperglycemic intrauterine environment also led to the impairment of glucose tolerance in the adult offspring. These metabolic abnormalities were transmitted to the next generations, suggesting that in utero exposure to maternal diabetes has an epigenetic impact. At the cellular level, some findings suggest an impaired pancreatic beta-cell mass and function. Several mechanisms such as defects in pancreatic angiogenesis and innervation, or modification of parental imprinting, may be implicated, acting either independently or in combination.

Conclusion: Thus, fetal exposure to maternal diabetes may contribute to the worldwide diabetes epidemic. Public health interventions targeting high-risk populations should focus on long-term follow-up of subjects who have been exposed in utero to a diabetic environment and on a better glycemic control during pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / metabolism*
  • Female
  • Fetus / metabolism*
  • Homeostasis
  • Humans
  • Insulin Resistance
  • Neovascularization, Physiologic
  • Pancreas / blood supply
  • Pancreas / innervation
  • Pregnancy


  • Blood Glucose