In vivo action of glibenclamide in obese subjects with mild type 2 (non-insulin dependent) diabetes.

In order to evaluate whether the hypoglycaemic action of glibenclamide during chronic treatment of obese subjects with NIDDM is primarily due to changes in the daytime insulin level, in insulin secretion or to changes in tissue sensitivity to insulin, we studied eight NIDD's (age 43 +/- 3 years, body mass index 31.4 +/- 2.6 kg/m2) inappropriately controlled by dietary treatment alone. Before and after three months of glibenclamide treatment, plasma glucose, insulin and C-peptide were measured hourly (0800 to 1600 hours) and in vivo insulin sensitivity was evaluated using the sequential euglycaemic clamp (insulin infusion: 0, 0.8, 3.2 mU/kg/min) in combination with 3-3H-glucose tracer technique. During glibenclamide treatment the mean daytime glucose level was reduced (11.2 +/- 0.5 versus 7.1 +/- 0.4 mmol/l, p less than 0.001) but not to normal (5.2 +/- 0.2 mmol/l, p less than 0.001). Before treatment the mean daytime insulin level was higher than normal (38 +/- 58 versus 24 +/- 2 microU/ml, p less than 0.05) and was increased by 79% (67 +/- 8 microU/ml, p less than 0.001) after three months of treatment. In contrast the mean C-peptide level was unchanged (1.40 +/- 0.13 versus 1.30 +/- 0.17 nmol/l, p = NS), although it was higher than normal on both occasions (0.84 +/- 0.09 nmol/l, p less than 0.05). The basal hepatic glucose production rate was normal before treatment (86 +/- 4 versus 82 +/- 3 mg.m-2.min-1 in normals, p = NS), and unchanged after glibenclamide treatment (80 +/- 3 mg.m-2.min-1, p = NS versus pretreatment level).(ABSTRACT TRUNCATED AT 250 WORDS)