Sex Difference In the Effect of Fetal Exposure to Maternal Diabetes on Insulin Secretion

We previously showed that fetal exposure to maternal type 1 diabetes (T1D) is associated with altered glucose-stimulated insulin secretion in adult offspring. Here, we investigated whether this β-cell defect displays a sex dimorphism. Twenty-nine adult nondiabetic offspring of T1D mothers (ODMs) were compared with 29 nondiabetic offspring of T1D fathers. We measured early insulin secretion in response to oral glucose and insulin secretion rate in response to intravenous glucose ramping. Insulin sensitivity and body composition were assessed by a euglycemic, hyperinsulinemic clamp and dual-energy X-ray absorptiometry, respectively. In response to oral glucose, male and female ODMs displayed a reduced insulin secretion. In contrast, in response to graded intravenous glucose infusion, only female ODMs (not males) exhibited decreased insulin secretion. There was no defect in response to combined intravenous arginine and glucose, suggesting that male and female ODMs exhibit a functional β-cell defect rather than a reduced β-cell mass. In conclusion, fetal exposure to maternal diabetes predisposes to β-cell dysfunction in adult male and female offspring. This β-cell defect is characterized by a sexual dimorphism following intravenous glucose stimulation.