Inheritance of Diabetes Mellitus as Consequence of Gestational Hyperglycemia in Rats

Our study investigated whether a deterioration of glucose homeostasis and insulin secretion in adult female rats from hyperglycemic dams could be transmitted to the next generation independent of genetic interferences. Dams (F₀) were rendered hyperglycemic by continuous glucose infusion during the last week of pregnancy. Females born of these rats (F₁) exhibited glucose intolerance and impaired insulin secretion in vivo at adulthood. When they were 3 mo old, they were mated with males born of control dams. During pregnancy, their glucose tolerance remained impaired compared with that of controls. Consequently, F₂ newborns of F₁ hyperglycemic dams showed the main features of newborns from diabetic mothers: they were hyperglycemie, hyperinsulinemic, and macrosomic. As adults, they displayed basal hyperglycemia and defective glucose tolerance and insulin secretion. This indicates that the long-range deteriorating effects on glucose homeostasis of gestationai hyperglycemia in the F₁generation are transmitted to the F₂ generation and suggests that a perturbed fetal metabolic environment contributes to the inheritance of diabetes mellitus.