Maternal hyperglycemia in pregnant rats: Its effect on growth and carbohydrate metabolism in the offspring

Abstract

Mild hyperglycemia during the last half of pregnancy was achieved by administration of streptozotocin to pregnant rats on the fifth day of gestation. Citrate buffer (vehicle for streptozotocin) was administered to control rats also on the fifth day of gestation. The pups born to the streptozotocin-treated mothers had higher birth weight, pancreatic insulin content, plasma insulin, and C-peptide concentrations compared with pups born to control mothers. The plasma glucose concentrations of the pups were similar between the two groups. The pups who were identified as macrosomic (birth weight > 1.7 SD than the mean of the control pups) maintained an accelerated postnatal growth through the first 10 weeks of age in female rats and in the first 3, and at 5 and 6 weeks of age for the male rats. The accelerated growth in the female rats was associated with higher perirenal-ovarian and salpingeal fat weight at 6 weeks. At 10 weeks of age, higher plasma insulin and glucose concentrations were observed following oral glucose challenge in both male and female macrosomic rats than in the control rats. At 12 weeks of age, only the female macrosomic rats showed abnormal glucose response due to peripheral insulin resistance. In the male rats at 12 weeks of age, a higher plasma insulin concentration in the macrosomic group was associated with a normal plasma glucose response to oral glucose challenge. We conclude that mild maternal hyperglycemia in rats resulted in fetal hyperinsulinemia and accelerated fetal growth. The macrosomic newborn, particularly the females, demonstrated persistence of accelerated postnatal growth with abnormal glucose tolerance probably as a result of peripheral insulin resistance.