Effect of glyburide on glycemic control, insulin requirement, and glucose metabolism in insulin-treated diabetic patients

Abstract

Glycemic control and glucose metabolism were examined in 5 patients with insulin-dependent diabetes mellitus (IDDM) and 8 insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients before and after 2 mo of therapy with glyburide (20 mg/day). Glycemic control was assessed by daily insulin requirement, 24-h plasma glucose profile, glucosuria, and glycosylated hemoglobin. Insulin secretion was evaluated by glucagon stimulation of C-peptide secretion, and insulin sensitivity was determined by a two-step euglycemic insulin clamp (1 and 10 mU .cntdot. kg-1 .cntdot. min-1) performed with indirect calorimetry and [3-3H]glucose. In the IDDM patients, the addition of glyburide produced no change in daily insulin dose (54 .+-. 8 vs. 53 .+-. 7 U/day), mean 24-h glucose level (177 .+-. 20 vs. 174 .+-. 29 mg/dl), glucosuria (20 .+-. 6 vs. 35 .+-. 12 g/day) or glycosylated hemoglobin (10.1 .+-. 1.0 vs. 9.5 .+-. 0.7%). Furthermore, there was no improvement in basal hepatic glucose production (2.1 .+-. 0.2 vs. 2.4 .+-. 0.1 mg .cntdot. kg-1 .cntdot. min-1), suppression of hepatic glucose production by low- and high-dose insulin infusion, or in any measure of total, oxidative, or nonoxidative glucose metabolism in the basal state or during insulin infusion. C-peptide levels were undetectable (< 0.01 pmol/ml) in the basal state and after glucagon infusion and remained undetectable after glyburide therapy. In contrast to the IDDM patients, the insulin-treated NIDDM subjects exhibited significant reductions in daily insulin requirement (72 .+-. 6 vs. 58 .+-. 9 U/day), mean 24-h plasma glucose concentration (153 .+-. 10 vs. 131 .+-. 5 mg/dl), glucosuria (14 .+-. 5 vs. 4 .+-. 1 g/day), and glycosylated hemoglobin (10.3 .+-. 0.7 vs. 8.0 .+-. 0.4%) after glyburide treatment (all P .ltoreq. .05). However, there was no change in basal hepatic glucose production (1.7 .+-. 0.1 vs. 1.7 .+-. 0.1 mg .cntdot. kg-1 .cntdot. min-1), suppression of hepatic glucose production by insulin, or insulin sensitivity during the two-step insulin-clamp study. Both basal (0.14 .+-. 0.05 vs. 0.32 .+-. 0.05 pmol/ml, P < .05) and glucagon-stimulated (0.24 .+-. 0.07 vs. 0.44 .+-. 0.09 pmol/ml) C-peptide levels rose after 2 mo of glyburide therapy and both were correlated with the decrease in insulin requirment (basal: r = .65, P = .08; glucagon stimulated: r = .93, P < .001). These data indicate that in IDDM subjects, the addition of glyburide to insulin does not affect insulin requirement, glycemic control, or insulin sensitivity. In contrast, in insulin-treated NIDDM patients, glyburide produces a modest decrease in insulin dose and improves glycemic control without altering insulin sensitivity. This improvment in glucose metabolism primarily reflects an increase in endogenous insulin secretion.