INFLUENCE OF SEVERE DIABETES-MELLITUS EARLY IN PREGNANCY IN THE RAT - EFFECTS ON INSULIN SENSITIVITY AND INSULIN-SECRETION IN THE OFFSPRING

We studied the influence of severe diabetes early in pregnancy on insulin sensitivity and insulin secretion in the offspring. Diabetes (blood glucose > 20 mmol/l) was induced in female Sprague-Dawley rats before mating. Diabetic dams were insulin treated during the second half of pregnancy (mean blood glucose 10.6 mmol/l). The offspring were reared by foster mothers. Offspring of both sexes were insulin resistant at four and seven months of age as evidenced by normal glucose tolerance after glucose (2 g/kg body weight intraperitoneally) concomitant with higher than normal rises in insulin levels. Regardless of fetal environment the male rats had higher glucose and insulin levels than the female rats. Insulin responses to glucose (27 mmol/l) in vitro in perfused pancreases were not increased by maternal diabetes, male gender or higher age. Conversely responses to 3-isobutyl-1-methylxanthine (1.0 mmol/l) were enhanced by all three conditions. The pancreatic content of insulin was only marginally affected by maternal diabetes. We conclude that severe diabetes during early pregnancy affects glucose homeostasis in the offspring primarily by diminishing insulin sensitivity and that susceptibility to this effect is not sex- or age-dependent.