Cretti A, Lehtovirta M, Bonora E, Brunato B, Zenti M G, Tosi F, Caputo M, Caruso B, Groop L C, Muggeo M, Bonadonna R C
University of Verona School of Medicine, Verona, Italy.
Eur J Clin Invest. 2001 May;31(5):405-16. doi: 10.1046/j.1365-2362.2001.00827.x.
To characterise the performance of beta-cell during a standard oral glucose tolerance test (OGTT).
Fifty-six subjects were studied. A minimal analogic model of beta-cell secretion during the OGTT was applied to all OGTTs (see below). The amount of insulin secreted over 120' in response to oral glucose (OGTT-ISR; Insulin Units 120'-1 m-2 BSA) and an index of beta-cell secretory 'force' (beta-Index; pmol.min-2.m-2 BSA) were computed with the aid of the model. In protocol A, 10 healthy subjects underwent two repeat 75 g OGTT with frequent (every 10'-15') blood sampling for glucose and C-peptide to test the reproducibility of OGTT-ISR and beta-Index with a complete or a reduced data set. In protocol B, 7 healthy subjects underwent three OGTTs (50, 100 or 150 g), to test the stability of the beta-Index under different glucose loads. In protocol C, 29 subjects (15 with normal glucose tolerance, 7 with impaired glucose tolerance and 7 with newly diagnosed type 2 diabetes) underwent two repeat 75 g OGTT with reduced (every 30' for 120') blood sampling to compare the reproducibility and the discriminant ratio (DR) of OGTT-ISR and beta-index with the insulinogenic index (IG-Index: Delta Insulin 30' - Basal/Delta Glucose 30' - Basal). In protocol D, 20 subjects (14 with normal glucose tolerance, 5 with impaired glucose tolerance and 1 with newly-diagnosed type 2 diabetes) underwent a 75 g OGTT and an intravenous glucose tolerance test (IVGTT) on separate days to explore the relationships between acute (0'-10') insulin response (AIR) during the IVGTT and beta-index and OGTT-ISR during the OGTT.
In all protocols, the minimal analogic model of C-peptide secretion achieved a reasonable fit of the experimental data. In protocol A, a good reproducibility of both beta-index and OGTT-ISR was observed with both complete and reduced (every 30') data sets. In protocol B, increasing the oral glucose load caused progressive increases in OGTT-ISR (from 2.63 +/- 0.70 to 5.11 +/- 0.91 Units.120'-1.m-2 BSA; P < 0.01), but the beta-index stayed the same (4.14 +/- 0.35 vs. 4.29 +/- 0.30 vs. 4.30 +/- 0.33 pmol.min-2.m-2 BSA). In protocol C, both OGTT-ISR and beta-index had lower day-to-day CVs (17.6 +/- 2.2 and 12.4 +/- 2.4%, respectively) and higher DRs (2.57 and 1.74, respectively) than the IG-index (CV: 35.5 +/- 6.3%; DR: 0.934). OGTT-ISR was positively correlated to BMI (P < 0.03), whereas beta-index was inversely related to both fasting and 2 h plasma glucose (P < 0.01 for both). In protocol D, beta-index, but not OGTT-ISR, was significantly correlated to AIR (r = 0.542, P < 0.02).
Analogically modelling beta-cell function during the OGTT provides a simple, useful tool for the physiological assessment of beta-cell function.
描述在标准口服葡萄糖耐量试验（OGTT）期间β细胞的功能表现。
对56名受试者进行了研究。将OGTT期间β细胞分泌的最小模拟模型应用于所有OGTT（见下文）。借助该模型计算了口服葡萄糖后120分钟内分泌的胰岛素量（OGTT-ISR；胰岛素单位120'-1 m-2体表面积）和β细胞分泌“力”指数（β指数；pmol.min-2.m-2体表面积）。在方案A中，10名健康受试者进行了两次重复的75克OGTT，频繁（每10'-15'）采集血糖和C肽样本，以测试完整或简化数据集下OGTT-ISR和β指数的可重复性。在方案B中，7名健康受试者进行了三次OGTT（50克、100克或150克），以测试不同葡萄糖负荷下β指数的稳定性。在方案C中，29名受试者（15名糖耐量正常、7名糖耐量受损和7名新诊断的2型糖尿病患者）进行了两次重复的75克OGTT，减少（每30'采集120'）采血，以比较OGTT-ISR和β指数与胰岛素生成指数（IG指数：Delta胰岛素30'-基础值/Delta葡萄糖30'-基础值）的可重复性和判别率（DR）。在方案D中，20名受试者（14名糖耐量正常、5名糖耐量受损和1名新诊断的2型糖尿病患者）在不同日期分别进行了75克OGTT和静脉葡萄糖耐量试验（IVGTT），以探讨IVGTT期间急性（0'-10'）胰岛素反应（AIR）与OGTT期间β指数和OGTT-ISR之间的关系。
在所有方案中，C肽分泌的最小模拟模型对实验数据的拟合效果合理。在方案A中，完整和简化（每30'）数据集下β指数和OGTT-ISR均具有良好的可重复性。在方案B中，增加口服葡萄糖负荷导致OGTT-ISR逐渐增加（从2.63±0.70增加到5.11±0.91单位·120'-1·m-2体表面积；P<0.01），但β指数保持不变（4.14±0.35对4.29±0.30对4.30±0.33 pmol.min-2.m-2体表面积）。在方案C中，与IG指数相比，OGTT-ISR和β指数的日间CV均较低（分别为17.6±2.2和12.4±2.4%），DR较高（分别为2.57和1.74）（CV：35.5±6.3%；DR：0.934）。OGTT-ISR与BMI呈正相关（P<0.03），而β指数与空腹和2小时血浆葡萄糖均呈负相关（两者P<0.01）。在方案D中，β指数而非OGTT-ISR与AIR显著相关（r=0.542，P<0.02）。
OGTT期间对β细胞功能进行模拟建模为β细胞功能的生理评估提供了一种简单、有用的工具。
