Department of Clinical Sciences, Lund University, B11 BMC, SE-221 84 Lund, Sweden.
J Clin Endocrinol Metab. 2012 Oct;97(10):3799-806. doi: 10.1210/jc.2012-2332. Epub 2012 Aug 1.
The dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits glucagon secretion at hyperglycemia but appears to enhance glucagon counterregulation during hypoglycemia in type 2 diabetes.
The objective of the investigation was to study whether vildagliptin also improves α-cell function in type 1 diabetes (T1D).
The study was a single-center, double-blind, randomized, placebo-controlled crossover study involving 28 patients with C-peptide negative and antibody positive T1D [21 males, seven females, glycosylated hemoglobin 57.9 mmol/mol (7.5%)]. Patients received vildagliptin (50 mg twice a day) or placebo as an add-on to their insulin therapy for 4 wk each. On d 28 of the respective treatment period, patients were served a standard meal (500 kcal) to raise the circulating incretin hormone levels followed by a hyperinsulinemic hypoglycemic clamp at 2.5 mmol/liter.
The increase in plasma glucagon levels during the 30-min hypoglycemic clamp (min 165-195 of the test) was measured.
During the meal, glucagon levels were lower with vildagliptin than with placebo (120 min area under the curve(glucagon) 2.4±0.2 vs. 2.6±0.2 nmol/liter×minutes, P=0.022 for between group difference). In contrast, during hypoglycemia, the glucagon counterregulation was not reduced by vildagliptin (increase in glucagon 1.5±1.0 pmol/liter with vildagliptin vs. 1.7±0.8 pmol/liter with placebo, P=NS). In addition, the counterregulatory responses in epinephrine, norepinephrine, cortisol, and pancreatic polypeptide were not different between the treatments. During the 4-wk treatment period, vildagliptin reduced the mean glycosylated hemoglobin, whereas there was no change with placebo [between group difference was -3.4±1.0 mmol/mol (-0.32±0.09%; P=0.002)] from baseline of 57.9 mmol/mol (7.5%).
Vildagliptin, although inhibiting glucagon secretion during hyperglycemia, does not compromise the glucagon counterregulatory response during hypoglycemia in T1D.
二肽基肽酶-4 抑制剂维格列汀在高血糖时抑制胰高血糖素分泌，但在 2 型糖尿病中似乎会增强低血糖时的胰高血糖素反调节作用。
本研究旨在探讨维格列汀是否也能改善 1 型糖尿病（T1D）患者的胰岛 α 细胞功能。
这是一项单中心、双盲、随机、安慰剂对照交叉研究，纳入了 28 例 C 肽阴性和抗体阳性的 T1D 患者（21 名男性，7 名女性，糖化血红蛋白 57.9mmol/mol[7.5%]）。患者在胰岛素治疗的基础上分别加用维格列汀（50mg，每日 2 次）或安慰剂治疗 4 周。在各自治疗期的第 28 天，患者服用标准餐（500kcal）以升高循环肠降血糖素激素水平，然后进行 2.5mmol/L 的高胰岛素低血糖钳夹试验。
测量 30 分钟低血糖钳夹试验（试验第 165-195 分钟）期间血浆胰高血糖素水平的升高。
在进餐期间，维格列汀组的胰高血糖素水平低于安慰剂组（120 分钟时胰高血糖素曲线下面积[glucagon] 2.4±0.2 比 2.6±0.2nmol/liter×min，组间差异 P=0.022）。相比之下，在低血糖期间，维格列汀并未降低胰高血糖素的反调节作用（胰高血糖素增加 1.5±1.0pmol/liter 用维格列汀治疗，1.7±0.8pmol/liter 用安慰剂治疗，P=NS）。此外，两种治疗方法之间肾上腺素、去甲肾上腺素、皮质醇和胰多肽的代偿反应没有差异。在 4 周治疗期间，维格列汀降低了平均糖化血红蛋白，而安慰剂组没有变化[组间差异为-3.4±1.0mmol/mol（-0.32±0.09%；P=0.002），基线为 57.9mmol/mol（7.5%）]。
尽管维格列汀在高血糖时抑制胰高血糖素分泌，但在 T1D 中并不影响低血糖时的胰高血糖素反调节反应。
