Vaag A A, Holst J J, Vølund A, Beck-Nielsen H B
Department of Endocrinology and Internal Medicine M, Odense University Hospital, Denmark.
Eur J Endocrinol. 1996 Oct;135(4):425-32. doi: 10.1530/eje.0.1350425.
The incremental glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses (areas under curves; AUCs) were determined during a standard 180-min 75-g oral glucose tolerance test in a group of 12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) and 13 matched controls without family history of diabetes using highly sensitive and specific radioimmunoassay hormone assays. Data were analysed using multifactor analysis of variance (ANOVA) to identify and correct for possible covariates and to correct for multiple comparisons. Fasting plasma GLP-1 and GIP concentrations were similar in all groups. The twins with frank NIDDM had a decreased incremental GLP-1 response during oral glucose ingestion compared with controls without family history of diabetes (AUC +/- SEM: 0.55 +/- 0.14 vs 1.17 +/- 0.25 (mmol/l) x min, p < 0.05). The incremental GLP-1 secretion in the non-diabetic twins was not significantly different from neither their NIDDM co-twins nor the controls without family history of diabetes. The incremental GIP responses were similar in all study groups. Gender was identified as the major independent covariate for incremental glucose, insulin, GIP and GLP-1 responses, with higher values of all parameters in females. Waist-to-hip ratio and body mass index (BMI) were identified as independent but oppositely directed covariates for the incremental GLP-1 responses (waist-to-hip ratio: r = 0.43, p < 0.02; BMI: r = -0.34, p = 0.06). Incremental GLP-1 responses correlated with incremental insulin responses in the combined study population (N = 37; R = 0.42, p = 0.01). In conclusion, a decreased intestinal GLP-1 secretion may contribute to the abnormal insulin secretion during oral glucose ingestion in NIDDM twins. However, decreased secretion of gut incretin hormones (GLP-1 or GIP) does not explain all of the defects of pancreatic insulin secretion in NIDDM patients/twins or in non-diabetic individuals (identical twins) with a genetic predisposition to NIDDM.
在一项标准的180分钟75克口服葡萄糖耐量试验中，使用高灵敏度和特异性的放射免疫分析激素检测方法，对12对同卵双胞胎（其中一对患有非胰岛素依赖型糖尿病（NIDDM），另一对未患）以及13名无糖尿病家族史的匹配对照者，测定了胰高血糖素样肽1（GLP - 1）和胃抑制多肽（GIP）的增量反应（曲线下面积；AUC）。使用多因素方差分析（ANOVA）对数据进行分析，以识别并校正可能的协变量，并校正多重比较。所有组的空腹血浆GLP - 1和GIP浓度相似。与无糖尿病家族史的对照者相比，患有明显NIDDM的双胞胎在口服葡萄糖期间的GLP - 1增量反应降低（AUC +/- SEM：0.55 +/- 0.14对1.17 +/- 0.25（mmol/l）×分钟，p < 0.05）。非糖尿病双胞胎的GLP - 1增量分泌与其患有NIDDM的双胞胎以及无糖尿病家族史的对照者相比，无显著差异。所有研究组的GIP增量反应相似。性别被确定为葡萄糖、胰岛素、GIP和GLP - 1增量反应 的主要独立协变量，女性所有参数的值更高。腰臀比和体重指数（BMI）被确定为GLP - 1增量反应的独立但方向相反的协变量（腰臀比：r = 0.43，p < 0.02；BMI：r = -0.34，p = 0.06）。在合并的研究人群中（N = 37），GLP - 1增量反应与胰岛素增量反应相关（R = 0.42，p = 0.01）。总之，肠道GLP - 1分泌减少可能导致NIDDM双胞胎口服葡萄糖期间胰岛素分泌异常。然而，肠道肠促胰岛素激素（GLP - 1或GIP）分泌减少并不能解释NIDDM患者/双胞胎或有NIDDM遗传易感性的非糖尿病个体（同卵双胞胎）胰腺胰岛素分泌的所有缺陷。
