Insulin resistance and impaired pancreatic β-cell function in adult offspring of women with diabetes in pregnancy

J Clin Endocrinol Metab. 2013 Sep;98(9):3793-801. doi: 10.1210/jc.2013-1536. Epub 2013 Jun 24.


Context: Offspring of women with diabetes during pregnancy have an increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.

Objective: We aimed to investigate the effects of intrauterine hyperglycemia on insulin secretion and action in adult offspring of mothers with diabetes.

Design, setting, and participants: A cohort of 587 Caucasian offspring, without known diabetes, was followed up at the age of 18-27 years. We included 2 groups exposed to maternal diabetes in utero: offspring of women with gestational diabetes mellitus (n = 167) or type 1 diabetes (n = 153). Two reference groups were included: offspring of women with risk factors for gestational diabetes mellitus but normoglycemia during pregnancy (n = 139) and offspring from the background population (n = 128).

Main outcome measures: Indices of insulin sensitivity and insulin release were calculated using insulin and glucose values from a standard oral glucose tolerance test (120 minutes, 75 g glucose). Pancreatic β-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices.

Results: Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes had reduced insulin sensitivity compared with offspring from the background population (both P < .005). We did not find any significant difference in absolute measures of insulin release. However, the disposition index was significantly reduced in both the diabetes-exposed groups (both P < .005).

Conclusion: Reduced insulin sensitivity as well as impaired pancreatic β-cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Adult Children
  • Child of Impaired Parents*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes, Gestational / physiopathology*
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / physiology*
  • Male
  • Pancreas / physiopathology*
  • Pregnancy
  • Pregnancy in Diabetics / physiopathology*
  • Risk Factors