Joy Nino G, Tate Donna B, Davis Stephen N
University of Maryland, Baltimore, Department of Medicine.
University of Maryland, Baltimore, Department of Medicine.
Metabolism. 2015 Jun;64(6):729-37. doi: 10.1016/j.metabol.2015.02.006. Epub 2015 Feb 26.
Reported rates of hypoglycemia in patients with type 2 diabetes mellitus are lower with glimepiride as compared to glyburide. The aim of this study was to determine whether physiologic differences in counterregulatory neuroendocrine and metabolic mechanisms during hypoglycemia provide a basis for the observed clinical differences between glimepiride and glyburide.
Non-diabetic volunteers (age 38±2years, BMI 26±1kg/m(2)) were studied in a single-blind fashion during separate 2day randomized protocols consisting of 2h hyperinsulinemic (9pmol/kg/min) euglycemic (4.9±0.1mmol) and hypoglycemic (2.9±0.1mmol/L) clamps. Individuals received biologically equivalent doses of glimepiride (4mg) or glyburide (10mg) 1h prior to each glucose clamp (n=11) as well as a control group of placebo studies. Glucose kinetics were calculated using D-Glucose-6-6d2.
Insulin and C-peptide levels were increased (p<0.05) during euglycemia in both sulfonylurea groups as compared to placebo. However, despite equivalent hypoglycemia, insulin and C-peptide levels were higher (p<0.05) only after glyburide. Glucagon responses and endogenous glucose production (EGP) were decreased (p<0.05) during hypoglycemia following glyburide administration as compared to glimepiride. Glyburide reduced (p<0.05) norepinephrine responses during euglycemic clamps. In addition combined epinephrine and norepinephrine responses during hypoglycemia were reduced (p<0.05) following glyburide as compared to placebo. Leptin levels fell by a greater amount (p<0.05) during hypoglycemia with both sulfonylureas as compared to placebo.
In summary, glimepiride and glyburide can both similarly increase insulin and C-peptide levels during hyperinsulinemic euglycemia. However, during moderate hyperinsulinemic hypoglycemia (2.9mmol/L) glyburide resulted in increased C-peptide and insulin, but blunted glucagon, sympathetic nervous system and EGP responses. We conclude that glyburide can acutely reduce key neuroendocrine and metabolic counterregulatory defenses during hypoglycemia in healthy individuals.
与格列本脲相比，使用格列美脲的2型糖尿病患者低血糖发生率更低。本研究旨在确定低血糖期间反调节神经内分泌和代谢机制的生理差异是否为观察到的格列美脲和格列本脲之间的临床差异提供依据。
对非糖尿病志愿者（年龄38±2岁，体重指数26±1kg/m²）进行单盲研究，在单独的为期2天的随机方案中，包括2小时高胰岛素血症（9pmol/kg/min）正常血糖（4.9±0.1mmol）和低血糖（2.9±0.1mmol/L）钳夹。在每次葡萄糖钳夹前1小时，个体接受生物等效剂量的格列美脲（4mg）或格列本脲（10mg）（n = 11），以及一个安慰剂研究对照组。使用D-葡萄糖-6-6d2计算葡萄糖动力学。
与安慰剂相比，两个磺脲类药物组在正常血糖期间胰岛素和C肽水平均升高（p<0.05）。然而，尽管低血糖程度相同，但仅在使用格列本脲后胰岛素和C肽水平更高（p<0.05）。与格列美脲相比，服用格列本脲后低血糖期间胰高血糖素反应和内源性葡萄糖生成（EGP）降低（p<0.05）。格列本脲在正常血糖钳夹期间降低（p<0.05）去甲肾上腺素反应。此外，与安慰剂相比，服用格列本脲后低血糖期间肾上腺素和去甲肾上腺素联合反应降低（p<0.05）。与安慰剂相比，两种磺脲类药物在低血糖期间瘦素水平下降幅度更大（p<0.05）。
总之，格列美脲和格列本脲在高胰岛素血症正常血糖期间均可同样增加胰岛素和C肽水平。然而，在中度高胰岛素血症低血糖（2.9mmol/L）期间，格列本脲导致C肽和胰岛素增加，但胰高血糖素、交感神经系统和EGP反应减弱。我们得出结论，格列本脲可在健康个体低血糖期间急性降低关键的神经内分泌和代谢反调节防御。
