Ahrén Bo, Pacini Giovanni, Foley James E, Schweizer Anja
Department of Medicine, Lund University, B11 BMC, SE-221 84 Lund, Sweden.
Diabetes Care. 2005 Aug;28(8):1936-40. doi: 10.2337/diacare.28.8.1936.
To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related beta-cell function and insulin sensitivity over 52 weeks in type 2 diabetes.
In a 12-week core study, placebo (n = 51) or vildagliptin (n = 56; 50 mg OD) was added to metformin treatment (1.5-3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at 0, 12, 24, and 52 weeks; glucose, insulin, and C-peptide were evaluated.
In subjects completing 52 weeks with participation in all meal tests (n = 57), HbA(1c) (A1C) decreased in the vildagliptin/metformin group (VM group, n = 31) but increased in the placebo/metformin group (PM group, n = 26; between-group difference -1.0 +/- 0.2%; P < 0.001; baseline of all subjects combined 7.7 +/- 0.1%). Also, fasting glucose decreased in the VM group but increased in the PM group (difference -0.9 +/- 0.3 mmol/l, P = 0.016; baseline 9.8 +/- 0.3 mmol/l). Insulin secretion (postmeal suprabasal area under the 0- to 30-min C-peptide curve divided by the 30-min increase in glucose) was increased in the VM group but was reduced in the PM group (difference +0.011 +/- 0.03 pmol/l 30 min/mmol/l, P = 0.018; baseline 0.036 +/- 0.02). Insulin sensitivity during meal ingestion (oral glucose insulin sensitivity) increased in the VM group but was not altered in the PM group (difference +27 +/- 4 ml x min(-1) x m(-2), P = 0.036; baseline 246 +/- 6). Insulin secretion related to insulin sensitivity (adaptation index) increased in the VM group but decreased in the PM group (difference +3.2 +/- 1.0, P = 0.040; baseline 9.1 +/- 0.5). The change in adaptation index correlated to the change in A1C (r = -0.39, P = 0.004).
This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves beta-cell function along with improved postmeal insulin sensitivity.
研究二肽基肽酶-4（DPP-4）抑制剂对2型糖尿病患者52周内与进餐相关的β细胞功能及胰岛素敏感性的影响。
在一项为期12周的核心研究中，在二甲双胍治疗（1.5 - 3.0mg/天）基础上加用安慰剂（n = 51）或维格列汀（n = 56；50mg每日一次）。71例患者随后进行了为期40周的延长期研究。在第0、12、24和52周进行进餐试验；评估血糖、胰岛素和C肽。
在完成52周且参与所有进餐试验的受试者（n = 57）中，维格列汀/二甲双胍组（VM组，n = 31）的糖化血红蛋白（HbA1c）（A1C）下降，而安慰剂/二甲双胍组（PM组，n = 26）升高（组间差异-1.0±0.2%；P < 0.001；所有受试者基线水平为7.7±0.1%）。此外，VM组空腹血糖下降，而PM组升高（差异-0.9±0.3mmol/l，P = 0.016；基线为9.8±0.3mmol/l）。VM组胰岛素分泌（0至30分钟C肽曲线下餐后超基础面积除以30分钟血糖升高值）增加，而PM组降低（差异+0.011±0.03pmol/l 30min/mmol/l，P = 0.018；基线为0.036±0.02）。进餐期间胰岛素敏感性（口服葡萄糖胰岛素敏感性）在VM组增加，而在PM组未改变（差异+27±4ml·min-1·m-2，P = 0.036；基线为246±6）。与胰岛素敏感性相关的胰岛素分泌（适应指数）在VM组增加，而在PM组降低（差异+3.2±1.0，P = 0.040；基线为9.1±0.5）。适应指数的变化与A1C的变化相关（r = -0.39，P = 0.004）。
本研究表明，2型糖尿病患者在二甲双胍基础上加用维格列汀进行52周的DPP-4抑制可改善β细胞功能，并提高餐后胰岛素敏感性。
