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Acute Effect of Glyburide on Insulin Sensitivity in Type I Diabetic Patients

Clinique Endocrinologique, Hôpital de I'Antiquaille Lyon, France

Address all correspondence and requests for reprint to: Dr. Dominique R. Garrel, Hôtel-Dieu de Montréal, 3840 St. Urbain. Montreal, Quebec, Canada H2W 1T8.

Possible extrapancreatic effects of glyburide on insulin action were studied in six patients with insulin-dependent diabetes mellitus. Each patient was studied on two separate occasions with continuous iv infusions of either glyburide (0.3 mg/h after a 1-mg iv bolus dose) or NaCl. During the studies blood glucose concentrations were controlled by a glucose-controlled infusion system (Biostator). The study included the 12-h period after the evening meal, followed by a 4-h period during which euglycemic hyperinsulinemic clamp studies were performed at two rates of insulin infusion: 1 and 10 mU/kg·min. During the glyburide infusion, the Biostator-determined insulin delivery rate was similar to that during the NaCl infusion for the first 6 h after the meal, but it decreased by 32% between the 6th and 12th hours after the meal. During the hyperinsulinemic clamp studies, glucose was delivered at a significantly higher rate when glyburide was infused; this was true for both rates of insulin infusion [5.6 ± 1.9 (±SD) vs. 3.6 ± 1.4 mg/kg·min and 12.1 ± 2.4 vs. 9.1 ± 2.1 mg/kg·min; P < 0.05, glyburide vs. NaCl, respectively]. Plasma C-peptide was undetectable in all patients during both studies. These results indicate that 1) glyburide has an acute effect on insulin action in insulin-dependent diabetic patients; and 2) this effect occurs at physiological as well as pharmacological insulin concentrations.

Received April 2, 1987.

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