The acute and chronic effects of sulfonylurea therapy in type II diabetic subjects

Although sulfonylurea agents have been used in the clinical management of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM) for over two decades, the mechanisms responsible for their hypoglycemic action remain controversial. We have quantitated glycemic control, endogenous insulin secretion in response to mixed meals, adipocyte insulin binding, insulin-mediated peripheral glucose disposal, and basal hepatic glucose output in 17 type II diabetic subjects before and after 3 mo of therapy with the second-generation, sulfonylurea compound glyburide in an attempt to identify the factors responsible for the clinical response to the drug. In addition, 9 subjects were treated for an additional 15 mo to see if the response to the drug changed with time. The mean fasting serum glucose level fell from an initial value of 264 +/- 17 mg/dl to 178 +/- 16 mg/dl after 3 mo of drug therapy. Endogenous insulin secretion increased in all subjects, but the increase was most marked in those subjects who continued to exhibit fasting hyperglycemia (fasting serum glucose greater than 175 mg/dl) after 3 mo of therapy. Adipocyte insulin binding was unchanged after 3 mo of therapy, while the maximal rate of peripheral glucose disposal was increased by 23%, indicating enhancement of peripheral insulin action at a postreceptor site(s). Basal hepatic glucose output showed a significant correlation with the fasting serum glucose level both before and after therapy (r = 0.86, P less than 0.001) and fell from 141 +/- 12 mg/m2/min before therapy to 107 +/- 11 mg/m2/min after 3 mo of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)