Effect of the discontinuation of long-term sulfonylurea treatment on blood glucose and insulin secretion in noninsulin-dependent diabetes mellitus.

The mechanism of the hypoglycemic action of sulfonylureas during long-term treatment was investigated in twenty-four patients with noninsulin-dependent diabetes mellitus treated for 1.5 to 19 yr in the out-patient clinic. The subjects received the first oral glucose tolerance test (OGTT) while on sulfonylureas and the second OGTT one month after their withdrawal. As the degree of elevation of the fasting plasma glucose level after withdrawal varied, the subjects were classified into two groups. Fourteen subjects showing an increase of more than 15 mg/dl were arbitrarily designated as group I, and the rest as group II. The mean fasting plasma glucose of group I was 134 +/- 4 mg/dl (mean +/- SE) and 194 +/- 14 mg/dl with and without sulfonylureas, respectively. Group II did no exhibit any significant change in fasting plasma glucose. A mean fasting serum IRI of either group was not changed. In group I, a mean glucose area of 807 +/- 31 mg . h/dl on OGTT increased significantly to 1121 +/- 72 mg . h/dl (p less than 0.001) and, the same time, a mean IRI area decreased significantly from 102 +/- 10 microU . h/ml to 73 +/- 7 microU . h/ml (p less than 0.001). The ratio of IRI area to glucose area, which might indicate the responsiveness of pancreatic B cells to hyperglycemia, was reduced on an average by 48% in group I. However, group II showed no significant change in the mean value of the glucose area, IRI area or the ratio one month after the discontinuation of sulfonylurea treatment. These findings suggest that the insulinotropic action of sulfonylureas is maintained even after long-term treatment and contributes to their antidiabetic effect.