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The Sulfonylurea Glyburide Induces Impairment of Glucagon and Growth Hormone Responses During Mild Insulin-Induced Hypoglycemia

¹ Department of Internal Medicine University Medical Center, Utrecht, the Netherlands
² Center for Biostatistics, University Medical Center, Utrecht, the Netherlands

OBJECTIVE—The sulfonylurea (SU) glyburide may cause severe and prolonged episodes of hypoglycemia. We aimed at investigating the impact of glyburide on glucose counterregulatory hormones during stepwise hypoglycemic clamp studies.

RESEARCH DESIGN AND METHODS—We performed stepwise hypoglycemic clamp studies in 16 healthy volunteers (7 women and 9 men aged 44 ± 10 years). We investigated counterregulatory hormonal and symptom responses at arterialized venous plasma glucose levels (PG) of 3.8, 3.2, and 2.6 mmol/l, comparing 10 mg glyburide orally and placebo in a double-blind, randomized crossover fashion.

RESULTS—The increase in plasma glucagon with time from PG = 3.8 onward was smaller for glyburide than for placebo (P = 0.014). Plasma glucagon area under the curve (AUC)_60–180 was lower after glyburide than after placebo (1,774 ± 715 vs. 2,161 ± 856 pmol · l^–1 · min, P = 0.014). From PG = 3.8 onward, plasma growth hormone (GH) levels with placebo were nearly two times (1.9 [95% CI 1.2–2.9]) as high as with glyburide (P = 0.011). AUC_60–180 for GH was lower after glyburide than after placebo (geometric mean [range] 665 [356–1,275] and 1,058 [392–1,818] mU · l^–1 · min, respectively; P = 0.04). No significant differences were observed for plasma cortisol, epinephrine and norepinephrine, or incremental symptom scores.

CONCLUSIONS—The SU glyburide induces multiple defects in glucose counterregulatory hormonal responses, notably decreases in both glucagon and GH release.

Abbreviations: ANOVA, analysis of variance • AUC, area under the curve • GH, growth hormone • PG, plasma glucose level • K_ATP, ATP-sensitive K⁺ channel • RIA, radioimmunoassay • SU, sulfonylurea • SUR, SU receptor

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