Mechanism of improvement in glucose metabolism after chronic glyburide therapy.

The effect of glyburide on glucose metabolism was examined in 10 non-insulin-dependent diabetic subjects (NIDDM) and 7 young, control subjects. After 3 mo of glyburide treatment in NIDDM, fasting plasma glucose declined from 198 to 141 mg/dl (P less than 0.01) without change in fasting insulin levels. Basal hepatic glucose production (HGP) was slightly elevated in NIDDM versus controls (2.35 versus 2.18 mg/kg X min, P = NS) and was positively correlated with the fasting glucose concentration (r = 0.93, P less than 0.001). With chronic glyburide therapy, HGP declined to 1.72 mg/kg X min (P less than 0.01 versus preglyburide) and remained highly correlated with the fasting glucose concentration (r = 0.85, P less than 0.005). Basal glucose clearance in NIDDM was reduced by 48% compared with age-matched controls (1.22 versus 2.32 ml/kg X min, P less than 0.001) and was unchanged after 3 mo of glyburide. Thus, the most important factor responsible for the decline in fasting plasma glucose concentration was an inhibition of hepatic glucose output. The decrease in basal hepatic glucose production and fasting plasma glucose concentration occurred without any change in fasting plasma insulin or C-peptide concentration. Insulin-mediated glucose metabolism (insulin clamp technique) was reduced by 55% in NIDDM (2.91 versus 6.39 mg/kg X min, P less than 0.001). After glyburide, insulin-mediated glucose metabolism increased by 26% to 3.67 mg/kg X min (P less than 0.01). This increase in tissue sensitivity to insulin was unassociated with any change in insulin binding to monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)