Untersuchungen zum Wirkungsmechanismus der kombinierten Gabe von Glibenclamid und Insulin bei Typ-II-Diabetikern mit Sekundärversagen auf die orale Behandlung

Summary

In a double-blind placebo-controlled cross-over study eight type II diabetics (three men, five women), of whom six were at the point of late failure to oral treatment, were given an insulin infusion of 22 U human insulin/patient for 45 min (∼7 mU/kg × min); 30 min before infusion either glibenclamide (1 tablet Euglucon N) or placebo was administered. Glucose in venous blood, C-peptide, insulin, and glibenclamide concentrations in the blood plasma were simultaneously determined over a period of 210 min. The monitoring of glucose was handled using a Biostator.

The insulin level reached a mean maximum of 400 to 500 µU/ml and was in a behavior of 100 µU/ml for 60 min. The areas under the concentration-time curves (AUCs) were practically identical in the two regimes. The blood glucose fell (in mean) from 260 mg/dl to 135 mg/dl and at the end of the experiment was in the range of 155 mg/dl. The glibenclamide concentrations reached maximal concentrations of 185 ng/ml 90 min after administration. The C-peptide concentrations fell in the placebo phase by more than 40%. In contrast, in the glibenclamide period there was at first a slight rise and later a slight marginal fall (initial, 2.0 ng/ml vs 1.9 ng/ml; 60 min, 1.3 ng/ml vs 1.8 ng/ml; 180 min, 1.2 ng/ml vs 1.8 ng/ml). Values after 90, 120, and 180 min were statistically different. The AUCs (0–180 min) were different (329 ng × min/ml vs 251 ng × min/ml). The inhibition of insulin secretion (measured by C-peptide) caused by exogenous insulin administration is largely abolished by glibenclamide. This mechanism could be a major cause for the reduction of the insulin requirement in type II diabetics that has been shown in numerous clinical studies during simultaneous treatment with glibenclamide.