THE ACUTE EFFECT OF PREPRANDIAL EXOGENOUS AND ENDOGENOUS SULFONYLUREA-STIMULATED INSULIN-SECRETION ON POSTPRANDIAL GLUCOSE EXCURSIONS IN PATIENTS WITH TYPE-2 DIABETES

Sulphonylureas improve glucose tolerance by stimulating insulin secretion. Whether improved glucose tolerance results from enhanced early insulin release or greater total insulin secretion is not clear. Insulin responses to a test meal in Type 2 diabetic subjects with and without a single dose (2.5 mg) of oral and intravenous glipizide were, therefore, measured. Intravenous glipizide enhanced early insulin release more than oral glipizide (1 34 % and 80 % vs control; p<0.01), whereas total insulin release was equally improved (78 % and 54 % vs control; p<0.01). Despite slight differences in insulin release, there was no difference in glucose tolerance (median area under concentration curve (AUC); 66.6 vs 61.9 mmol x min l-1; NS). The test meal was repeated after a bolus of intravenous insulin at the beginning of the meal. This allowed comparison of the effect of exogenous and endogenous insulin supply on postprandial glucose excursions. In spite of an early and fivefold larger rise in serum insulin after intravenous administration of the hormone than after intravenous glipizide (725 % vs 134 %; p<0.01), postprandial glucose was no better than after glipizide (median AUC; 87.8 vs 66.6 mmol x min l-1; NS). In contrast, glucose tolerance was better after oral glipizide compared to intravenous insulin (median AUC; 61.9 vs 87.8 mmol x min l-1; p<0.05). In conclusion, the total amount of insulin secreted seems more important than the timing of the insulin release for the postprandial glucose tolerance in Type 2 diabetic subjects. Neither endogenous nor peripheral pre-meal supply of insulin could normalize postprandial glucose excursions in patients with Type 2 diabetes.