Impaired glucose homeostasis in adult rats from hyperglycemic mothers

The purpose of our study was to investigate whether nondiabetic gestational hyperglycemia during fetal life could have additional effects on glucose homeostasis and insulin secretion in the adult rat. Hyperglycemia without the main other metabolic disorders and vascular injuries associated with diabetes was produced in unrestrained pregnant rats by continuous glucose infusion during the last week of pregnancy. Control rats were infused with distilled water. Compared with controls, the newborns from hyperglycemic rats were hyperglycemic and hyperinsulinemic. When studied longitudinally up to 3 mo, they showed slightly but significantly increased basal plasma glucose levels and normal basal insulin concentrations compared with controls. Glucose tolerance and insulin secretion in response to a glucose load (0.5 mg/kg, i.v.) were altered: Plasma glucose values were more increased at 5 min and remained higher 90 min after glucose injection; incremental plasma insulin values and the insulinogenic indexes (delta IRI/delta G) were always lower in rats from hyperglycemic mothers than in controls. These alterations were more and more marked with advancing age (1-3 mo). These data show that gestational hyperglycemia may lead to persistent impairment of glucose homeostasis and insulin secretion in the adult rat.