Longitudinal evaluation of the effects of sulfonylurea therapy in subjects with type II diabetes mellitus.
Despite more than a quarter of a century of use in managing type II diabetes, the mechanism responsible for the hypoglycemic action of sulfonylurea agents remains controversial. To identify factors responsible for the clinical response to the drug, glycemic control, endogenous insulin secretion in response to mixed meals, adipocyte insulin binding, insulin-mediated peripheral glucose disposal as well as basal hepatic glucose output were assessed in 17 type II diabetic subjects before and after three months of therapy with glyburide, a second-generation sulfonylurea. To determine if the response to the drug changed with time, nine of the subjects were treated for an additional 15 months. Glyburide therapy increased endogenous insulin secretion, increased adipocyte insulin binding after 18 but not three months of therapy, enhanced peripheral insulin action by acting primarily at a post-receptor site, and reduced basal hepatic glucose output. The increase in post-receptor function and the reduction of basal hepatic glucose output appear to be the crucial determinants of the clinical response to the sulfonylurea; the response pattern to sulfonylurea compounds can vary as a function of the duration of treatment. An accelerated rate of basal hepatic glucose output appears to be the major cause of secondary failure in glyburide-treated patients.
D000273:Adipose Tissue / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy*; D005947:Glucose / Q000096:biosynthesis; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D008137:Longitudinal Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013453:Sulfonylurea Compounds; D005947:Glucose; D005905:Glyburide