Mechanism of exercise-induced hypoglycemia during sulfonylurea treatment

Exercise-induced hypoglycemia in diabetic patients on sulfonylurea treatment is not uncommon. However, its pathophysiology has not been examined. We studied 9 postabsorptive nondiabetic subjects after oral administration of 1.75 mg glyburide (glibenclamide) (protocol A), during 60 min of leg exercise on a bicycle ergometer at a work load of 80 +/- 10 W (protocol B), and during a combination of these conditions (protocol C). Serum glibenclamide levels rose to similar levels (160 ng/ml) with protocols A and C. Heart rate, blood pressure, and blood lactate levels increased immediately after onset of exercise and were comparable under conditions of protocols B and C. Serum insulin levels fell during protocol B from 6.1 +/- 0.6 to 4.0 +/- 0.3 microU/ml (P less than .001) but increased from 6.5 +/- 0.6 to 12.3 +/- 2.8 microU/ml during protocol A and from 6.6 +/- 0.6 to 12.7 +/- 4.3 microU/ml during protocol C, P less than .001. Maximal levels were reached at 80 min under both conditions. Comparable responses were seen for serum C-peptide concentrations. Blood glucose concentrations did not change during exercise alone. Glycemia decreased markedly after administration of the drug reaching a nadir of 49 +/- 3 mg/dl with protocol A and a nadir of 46 +/- 3 mg/dl under protocol C. However, the nadir was reached 80 min after oral ingestion of the drug when exercise and glyburide were combined, compared to 110 min (P less than .01) after ingestion of the drug alone.(ABSTRACT TRUNCATED AT 250 WORDS)