Zander Mette, Madsbad Sten, Madsen Jan Lysgaard, Holst Jens Juul
Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Lancet. 2002 Mar 9;359(9309):824-30. doi: 10.1016/S0140-6736(02)07952-7.
Glucagon-like peptide 1 (GLP-1) has been proposed as a treatment for type 2 diabetes. We have investigated the long-term effects of continuous administration of this peptide hormone in a 6-week pilot study.
20 patients with type 2 diabetes were alternately assigned continuous subcutaneous infusion of GLP-1 (n=10) or saline (n=10) for 6 weeks. Before (week 0) and at weeks 1 and 6, they underwent beta-cell function tests (hyperglycaemic clamps), 8 h profiles of plasma glucose, insulin, C-peptide, glucagon, and free fatty acids, and appetite and side-effect ratings on 100 mm visual analogue scales; at weeks 0 and 6 they also underwent dexascanning, measurement of insulin sensitivity (hyperinsulinaemic euglycaemic clamps), haemoglobin A(1c), and fructosamine. The primary endpoints were haemoglobin A(1c) concentration, 8-h profile of glucose concentration in plasma, and beta-cell function (defined as the first-phase response to glucose and the maximum insulin secretory capacity of the cell). Analyses were per protocol.
One patient assigned saline was excluded because no veins were accessible. In the remaining nine patients in that group, no significant changes were observed except an increase in fructosamine concentration (p=0.0004). In the GLP-1 group, fasting and 8 h mean plasma glucose decreased by 4.3 mmol/L and 5.5 mmol/L (p<0.0001). Haemoglobin A(1c) decreased by 1.3% (p=0.003) and fructosamine fell to normal values (p=0.0002). Fasting and 8 h mean concentrations of free fatty acids decreased by 30% and 23% (p=0.0005 and 0.01, respectively). Gastric emptying was inhibited, bodyweight decreased by 1.9 kg, and appetite was reduced. Both insulin sensitivity and beta-cell function improved (p=0.003 and p=0.003, respectively). No important side-effects were seen.
GLP-1 could be a new treatment for type 2 diabetes, though further investigation of the long-term effects of GLP-1 is needed.
胰高血糖素样肽1（GLP-1）已被提议用于治疗2型糖尿病。我们在一项为期6周的初步研究中调查了持续给予这种肽类激素的长期效果。
20例2型糖尿病患者被交替分配接受GLP-1持续皮下输注（n = 10）或生理盐水（n = 10），为期6周。在第0周（基线）、第1周和第6周，他们接受了β细胞功能测试（高血糖钳夹试验）、血浆葡萄糖、胰岛素、C肽、胰高血糖素和游离脂肪酸的8小时谱分析，以及使用100毫米视觉模拟量表进行的食欲和副作用评分；在第0周和第6周，他们还接受了地塞米松扫描、胰岛素敏感性测量（高胰岛素正常血糖钳夹试验）、糖化血红蛋白A1c和果糖胺检测。主要终点为糖化血红蛋白A1c浓度、血浆葡萄糖8小时谱以及β细胞功能（定义为对葡萄糖的第一相反应和细胞的最大胰岛素分泌能力）。分析按方案进行。
1例分配接受生理盐水的患者因无法找到可用静脉而被排除。在该组其余9例患者中，除果糖胺浓度升高外（p = 0.0004），未观察到显著变化。在GLP-1组中，空腹和8小时平均血浆葡萄糖分别降低了4.3 mmol/L和5.5 mmol/L（p < 0.0001）。糖化血红蛋白A1c降低了1.3%（p = 0.003），果糖胺降至正常水平（p = 0.0002）。空腹和8小时平均游离脂肪酸浓度分别降低了30%和23%（分别为p = 0.0005和0.01）。胃排空受到抑制，体重下降了1.9 kg，食欲降低。胰岛素敏感性和β细胞功能均得到改善（分别为p = 0.003和p = 0.003）。未观察到重要的副作用。
GLP-1可能是2型糖尿病的一种新治疗方法，不过仍需要对GLP-1的长期效果进行进一步研究。
