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

Context:Offspring of women with diabetes during pregnancy have increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate 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 two 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 GDM, but normo-glycemia 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 gram glucose). Pancreatic beta-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 <0.005). 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 <0.005).Conclusion:Reduced insulin sensitivity as well as impaired pancreatic beta cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy.