Trial of sulfonylurea in combination with insulin in the therapy of diabetes type I and II. Evidence against a primary extrapancreatic receptor effect

Abstract

Recently in vitro evidence has been presented that sulfonylurea derivatives exert their chronic extrapancreatic effect by increasing the number of cellular insulin receptors. To ascertain if this receptor effect holds in vivo, we performed a randomized double-blind study on 21 type I (0.3 ng/ml residual C-peptide secretory capacity after glucose/glibenclamide stimulation), and on 19 insulin treated type II (2.0 ng/ml C-peptide) diabetics. The patients received for six weeks 10 mg/d of glibenclamide in addition to insulin. Insulin binding was initially lower in type II (4.7 +/- 0.75% per 10(7) monocytes and 6.39 +/- 1.08% per 4.5 X 10(9) erythrocytes) than in type I diabetic patients (5.1 +/- 0.48% and 7.95 +/- 0.88% respectively) and in 12 normal subjects (5.25 +/- 0.48 and 8.1 +/- 0.94% respectively). Glibenclamide normalized the number of monocyte receptors (from 4.14 to 5.49 X 10(4) sites/cell) in type II patients, but was without effect in type I diabetics. Blood glucose was significantly reduced (240 to 182 mg/dl; p = 0.02) in the type II group with a concomitant decrease in glycosylated hemoglobin from 12.4 to 10.5% (p = 0.01). Most of the effect occurred during the first week of treatment. Glibenclamide was the more effective the worse the initial metabolic state (r = -0.93; p = 0.001). Erythrocyte insulin receptors decreased markedly in both groups, perhaps due to a sulfonyl urea-induced change in erythrocyte plasma survival time. It is concluded that sulfonylurea treatment is a valuable adjunct in reducing the insulin resistance in insulin treated type II diabetics. The effect depends on the availability of endogenous insulin, thus exhibiting only partly extrapancreatic character.(ABSTRACT TRUNCATED AT 250 WORDS)