Ahrén Bo, Schweizer Anja, Dejager Sylvie, Dunning Beth E, Nilsson Peter M, Persson Margaretha, Foley James E
Department of Clinical Sciences, Lund University, Lund, Sweden.
J Clin Endocrinol Metab. 2009 Apr;94(4):1236-43. doi: 10.1210/jc.2008-2152. Epub 2009 Jan 27.
Dipeptidyl peptidase-4 inhibitors act by increasing plasma levels of glucagon-like peptide-1 and suppressing excessive glucagon secretion in patients with type 2 diabetes. However, their effects on the glucagon response to hypoglycemia are not established.
The aim of the study was to assess effects of the dipeptidyl peptidase-4 inhibitor vildagliptin on alpha-cell response to hyper- and hypoglycemia.
We conducted a single-center, randomized, double-blind, placebo-controlled, two-period crossover study of 28-d treatment, with a 4-wk between-period washout.
We studied drug-naive patients with type 2 diabetes and baseline glycosylated hemoglobin of 7.5% or less.
Participants received vildagliptin (100 mg/d) or placebo as outpatients. PRIMARY OUTCOME MEASURE(S): We measured the following: 1) change in plasma glucagon levels during hypoglycemic (2.5 mm glucose) clamp; and 2) incremental (Delta) glucagon area under the concentration-time curve from time 0 to 60 min (AUC(0-60 min)) during standard meal test. Before the study, it was hypothesized that vildagliptin would suppress glucagon secretion during meal tests and enhance the glucagon response to hypoglycemia.
The mean change in glucagon during hypoglycemic clamp was 46.7 +/- 6.9 ng/liter with vildagliptin treatment and 33.9 +/- 6.7 ng/liter with placebo; the between-treatment difference was 12.8 +/- 7.0 ng/liter (P = 0.039), representing a 38% increase with vildagliptin. In contrast, the mean glucagon DeltaAUC(0-60 min) during meal test with vildagliptin was 512 +/- 163 ng/liter x min vs. 861 +/- 130 ng/liter x min with placebo; the between-treatment difference was -349 +/- 158 ng/liter x min (P = 0.019), representing a 41% decrease with vildagliptin.
Vildagliptin enhances alpha-cell responsiveness to both the suppressive effects of hyperglycemia and the stimulatory effects of hypoglycemia. These effects likely contribute to the efficacy of vildagliptin to improve glycemic control as well as to its low hypoglycemic potential.
二肽基肽酶 - 4抑制剂通过提高2型糖尿病患者血浆胰高血糖素样肽 - 1水平并抑制过度的胰高血糖素分泌发挥作用。然而，它们对胰高血糖素对低血糖反应的影响尚未明确。
本研究旨在评估二肽基肽酶 - 4抑制剂维格列汀对α细胞对高血糖和低血糖反应的影响。
我们进行了一项单中心、随机、双盲、安慰剂对照、为期28天治疗的两阶段交叉研究，两阶段之间有4周的洗脱期。
我们研究了未接受过药物治疗、2型糖尿病且基线糖化血红蛋白为7.5%或更低的患者。
参与者作为门诊患者接受维格列汀（100mg/天）或安慰剂治疗。
我们测量了以下指标：1）低血糖钳夹期间（血糖2.5mmol/L）血浆胰高血糖素水平的变化；2）标准餐试验期间从0到60分钟浓度 - 时间曲线下的增量（Δ）胰高血糖素面积（AUC(0 - 60分钟)）。在研究之前，假设维格列汀会在餐试验期间抑制胰高血糖素分泌并增强胰高血糖素对低血糖的反应。
维格列汀治疗期间低血糖钳夹时胰高血糖素的平均变化为46.7±6.9ng/升，安慰剂组为33.9±6.7ng/升；治疗组间差异为12.8±7.0ng/升（P = 0.039），维格列汀组增加了38%。相比之下，维格列汀餐试验期间的平均胰高血糖素ΔAUC(0 - 60分钟)为512±163ng/升·分钟，安慰剂组为861±130ng/升·分钟；治疗组间差异为 - 349±158ng/升·分钟（P = 0.019），维格列汀组降低了41%。
维格列汀增强了α细胞对高血糖抑制作用和低血糖刺激作用的反应性。这些作用可能有助于维格列汀改善血糖控制的疗效及其低血糖风险低的特点。
