Meneilly Graydon S, Greig Nigel, Tildesley Hugh, Habener Joel F, Egan Josephine M, Elahi Dariush
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Diabetes Care. 2003 Oct;26(10):2835-41. doi: 10.2337/diacare.26.10.2835.
Glucagon-like peptide 1 (GLP-1) is an insulinotropic gut hormone that, when given exogenously, may be a useful agent in the treatment of type 2 diabetes. We conducted a 3-month trial to determine the efficacy and safety of GLP-1 in elderly diabetic patients.
A total of 16 patients with type 2 diabetes who were being treated with oral hypoglycemic agents were enrolled. Eight patients (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) remained on usual glucose-lowering therapy and eight patients (aged 73 +/- 1 years, BMI 27 +/- 1 kg/m(2)), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol x kg(-1). h(-1). Patients recorded their capillary blood glucose (CBG) levels (four times per day, 3 days per week) and whenever they perceived hypoglycemic symptoms. The primary end points were HbA(1c) and CBG determinations. Additionally, changes in beta-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined.
HbA(1c) levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of <or=3.6 mmol/l during the study, and only 1 such measurement (3.5 mmol/l) was recorded in the GLP-1 group. Infusion of GLP-1 enhanced glucose-induced insulin secretion (pre: 119 +/- 21; post: 202 +/- 51 pmol/l; P < 0.05) and insulin-mediated glucose disposal (pre: 29.8 +/- 3.3; post: 35.9 +/- 2.3 micromol x kg(-1 x min(-1); P < 0.01). No effect of GLP-1 treatment was seen on the fasting plasma ghrelin levels. Although plasma ghrelin levels decreased during both portions of the clamp, a drug effect was not present.
A GLP-1 compound is a promising therapeutic option for elderly diabetic patients.
胰高血糖素样肽1（GLP-1）是一种促胰岛素分泌的肠促胰素，外源性给予时可能是治疗2型糖尿病的有效药物。我们进行了一项为期3个月的试验，以确定GLP-1在老年糖尿病患者中的疗效和安全性。
共纳入16例正在接受口服降糖药治疗的2型糖尿病患者。8例患者（年龄75±2岁，体重指数27±1kg/m²）继续接受常规降糖治疗，8例患者（年龄73±1岁，体重指数27±1kg/m²）在停用降糖药物后，接受连续皮下输注GLP-1治疗12周。最大剂量为120pmol·kg⁻¹·h⁻¹。患者记录其毛细血管血糖（CBG）水平（每天测4次，每周测3天）以及出现低血糖症状的时间。主要终点为糖化血红蛋白（HbA1c）和CBG测定。此外，还检测了β细胞对葡萄糖的敏感性、外周组织对胰岛素的敏感性以及血浆胃饥饿素水平的变化。
两组患者的HbA1c水平（7.1%）和体重均得到同等程度的维持。常规治疗组在研究期间共有87次CBG测量值≤3.6mmol/l，而GLP-1组仅记录到1次这样的测量值（3.5mmol/l）。输注GLP-1可增强葡萄糖诱导的胰岛素分泌（输注前：119±21；输注后：202±51pmol/l；P<0.05）以及胰岛素介导的葡萄糖处置（输注前：29.8±3.3；输注后：35.9±2.3μmol·kg⁻¹·min⁻¹；P<0.01）。GLP-1治疗对空腹血浆胃饥饿素水平无影响。尽管在钳夹试验的两个阶段血浆胃饥饿素水平均下降，但不存在药物效应。
GLP-1化合物是老年糖尿病患者一种有前景的治疗选择。
