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

Offspring of women with diabetes during pregnancy have an increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.We aimed to investigate the effects of intrauterine hyperglycemia on insulin secretion and action in adult offspring of mothers with diabetes.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).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.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).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.