Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
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DOI：
10.1210/jc.86.8.3717
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发表时间：
2001-08-01
影响因子：
5.8
通讯作者：
Holst, JJ
中科院分区：
文献类型：
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作者：
Toft-Nielsen, MB;Damholt, MB;Holst, JJ
为了阐明2型糖尿病中肠促胰岛素作用减弱的原因，我们研究了54例异质性2型糖尿病患者在4小时混合餐试验期间肠促胰岛素激素胰高血糖素样肽-1和葡萄糖依赖性促胰岛素多肽的分泌，并测量了非酯化脂肪酸和胰岛素、C肽、胰多肽和葡萄糖的血浆浓度，33例匹配的正常糖耐量对照受试者和15例不匹配的糖耐量受损受试者。在开始进餐后0-240分钟，患者的胰高血糖素样肽-1反应曲线下面积显著降低（2482 +/- 145与3101 +/- 198 pmol/L-240 min; P = 0.024）。此外，葡萄糖依赖性促胰岛素多肽的曲线下面积略微降低。在多元回归分析中，糖尿病、体重指数、男性、胰岛素曲线下面积（负面影响）、葡萄糖依赖性促胰岛素多肽曲线下面积（负面影响）和胰高血糖素曲线下面积（正面影响）的模型解释了胰高血糖素样肽-1反应的42%的变异性。糖耐量受损受试者是高胰岛素血症，通常表现出与糖尿病患者相同的异常，但程度较轻。我们的结论是，2型糖尿病患者的餐后胰高血糖素样肽-1反应降低，这可能有助于降低肠促胰岛素在2型糖尿病中的作用。
To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter-240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.