Effect of Glyburide on Glycemic control, insulin requirement, and glucose metabolism in insulin-treated diabetic patients

D. C. Simonson, S. Delprato, P. Castellino, L. Groop, R. A. DeFronzo

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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 kg-1 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 kg-1 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 ≤ .05). However, there was no change in basal hepatic glucose production (1.7 ± 0.1 vs. 1.7 ± 0.1 mg kg-1 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 requirement (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 improvement in glucose metabolism primarily reflects an increase in endogenous insulin secretion.

Original languageEnglish (US)
Pages (from-to)136-145
Number of pages10
Issue number2
StatePublished - Dec 1 1987
Externally publishedYes


ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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