Nauck M A, Sauerwald A, Ritzel R, Holst J J, Schmiegel W
Department of Medicine, Ruhr-University, Knappschafts-Krankenhaus, Bochum, Germany.
Diabetes Care. 1998 Nov;21(11):1925-31. doi: 10.2337/diacare.21.11.1925.
Glucagon-like peptide 1 (GLP-1) has glucose-dependent insulinotropic and glucagonostatic actions in type 2 diabetic patients on diet and on oral agents. It is not known, however, whether after secondary sulfonylurea failure, GLP-1 is still effective.
Therefore, 10 type 2 diabetic patients (6 women, 4 men; age 65+/-10 years, BMI 30.4+/-5.1 kg/m2, HbA1c 8.2+/-1.5%, 6+/-3 [2-13] years after starting insulin treatment) were examined in the fasting state after discontinuing NPH insulin on the evening before the two study days. GLP-1 (1.2 pmol x kg(-1) x min(-1) or placebo (NaCl with 1% human serum albumin) were infused over 6 h. Plasma glucose (glucose oxidase) insulin (IMx), and C-peptide (enzyme-linked immunosorbent assay) were measured. Statistical analysis was performed using repeated measures analysis of variance.
Fasting plasma glucose was 9.4+/-0.5 mmol/l and was reduced by GLP-1 to 5.3+/-0.3 (3.9-7.3) mmol/l (placebo: 8.2+/-0.7 mmol/l; P < 0.0001). GLP-1 transiently increased insulin (from 115+/-31 to 222+/-64 pmol/l at 150 min; P < 0.0001) and C-peptide (from 1.00+/-0.12 to 1.90+/-0.23 nmol/l at 120 min; P < 0.0001) with no effect of placebo. Glucagon and free fatty acids were lowered transiently. After normalization of plasma glucose, insulin and C-peptide concentrations became lower again during the ongoing administration of exogenous GLP-1, and no hypoglycemia occurred.
It is concluded that exogenous GLP-1 effectively lowers plasma glucose concentrations in advanced type 2 diabetes long after sulfonylurea secondary failure. These findings may broaden the applicability of GLP-1-derived drugs as a new treatment to nearly all type 2 diabetic patients.
胰高血糖素样肽1（GLP-1）对接受饮食和口服药物治疗的2型糖尿病患者具有葡萄糖依赖性促胰岛素分泌和抑制胰高血糖素分泌的作用。然而，在磺脲类药物继发失效后，GLP-1是否仍然有效尚不清楚。
因此，对10例2型糖尿病患者（6例女性，4例男性；年龄65±10岁，体重指数30.4±5.1kg/m2，糖化血红蛋白8.2±1.5%，开始胰岛素治疗后6±3[2-13]年）进行了研究。在两个研究日的前一晚停用中性鱼精蛋白锌胰岛素后，于空腹状态下对患者进行检查。GLP-1（1.2pmol·kg-1·min-1）或安慰剂（含1%人血清白蛋白的氯化钠）持续输注6小时。测定血浆葡萄糖（葡萄糖氧化酶法）、胰岛素（免疫比浊法）和C肽（酶联免疫吸附测定法）。采用重复测量方差分析进行统计分析。
空腹血糖为9.4±0.5mmol/l，GLP-1可将其降至5.3±0.3（3.9-7.3）mmol/l（安慰剂组：8.2±0.7mmol/l；P<0.0001）。GLP-1可使胰岛素（150分钟时从115±31pmol/l升至222±64pmol/l；P<0.0001）和C肽（120分钟时从1.00±0.12nmol/l升至1.90±0.23nmol/l；P<0.0001）短暂升高，而安慰剂无此作用。胰高血糖素和游离脂肪酸短暂降低。血糖正常化后，在持续输注外源性GLP-1期间，胰岛素和C肽浓度再次降低，且未发生低血糖。
得出结论，在磺脲类药物继发失效很久后的晚期2型糖尿病患者中，外源性GLP-1可有效降低血浆葡萄糖浓度。这些发现可能会扩大GLP-1衍生药物作为一种新治疗方法对几乎所有2型糖尿病患者的适用性。
