LONG-TERM CONSEQUENCES IN OFFSPRING OF DIABETES IN PREGNANCY - STUDIES WITH SYNGENEIC ISLET-TRANSPLANTED STREPTOZOTOCIN-DIABETIC RATS

To study the long term effects of exposure to maternal hyperglycemia a nd insulin deficiency in utero, we used the syngeneic islet transplant ed streptozotocin-diabetic rat model of diabetes in pregnancy and exam ined insulin secretion and action in 6-month-old offspring. Female rat s were rendered diabetic with streptozotocin and then transplanted wit h 2500, 750, or 500 islets. Control animals were also studied, and one group whose islet transplants failed remained diabetic. During pregna ncy, plasma glucose levels in the diabetic rats and the groups receivi ng 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/- 0.5 mmol/liter, respectively, all significantly greater than the control value (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet group was 6.2 +/- 0.2 mmol/liter, which was not signifi cantly higher than the control value. When the offspring were studied at 6 months, there was no significant difference between groups in eit her glucose or insulin levels after iv glucose, although acute insulin secretion tended to be higher in the offspring of the diabetic animal s. A study of insulin action with the euglycemic clamp at two insulin levels showed that insulin sensitivity was reduced in the offspring of diabetic animals us. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mu mol /liter x 100/kg/min . pmol/liter; P < 0.05). Insulin sensitivity was a lso significantly reduced in the 2500, 750, and 500 islet group offspr ing (4.81 +/- 0.57, 4.82 +/- 0.64, and 4.01 +/- 0.63 mu mol/liter x 10 0/kg/min . pmol/liter; P < 0.05) compared to that in the control. Ther e were no differences in insulin sensitivity between male and female a nimals. In summary, animals displaying maternal insulin deficiency hav e offspring who are insulin resistant without any evidence of iv gluco se intolerance or diminished insulin secretion.