Mari Andrea, Schmitz Ole, Gastaldelli Amalia, Oestergaard Torben, Nyholm Birgit, Ferrannini Ele
Consiglio Nazionale delle Ricerche Institute of Systems Science and Biomedical Engineering, 35127 Padua, Italy.
Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1159-66. doi: 10.1152/ajpendo.00093.2002. Epub 2002 Aug 6.
We investigated beta-cell function and its relationship to insulin sensitivity in 17 normal volunteers. For insulin secretion (derived by C-peptide deconvolution), a mathematical model was applied to 24-h triple-meal tests (MT) as well as oral glucose tolerance tests (OGTT); insulin sensitivity was assessed by the euglycemic insulin clamp technique. The beta-cell model featured a glucose concentration-insulin secretion dose response (characterized by secretion at 5 mM glucose and slope), a secretion component proportional to the glucose concentration derivative, and a time-dependent potentiation factor (modulating the dose response and accounting for effects of sustained hyperglycemia and incretins). The beta-cell dose-response functions estimated from the whole 24-h MT, the first 2 h of the MT, and the OGTT differed systematically, because a different potentiation factor was involved. In fact, potentiation was higher than average during meals (1.6 +/- 0.1-fold during the first meal) and had a different time course in the MT and OGTT. However, if potentiation was accounted for, the 24- and 2-h MT and the OGTT yielded similar dose responses, and most beta-cell function parameters were intercorrelated (r = 0.50-0.86, P < or = 0.05). The potentiation factor was found to be related to plasma glucose-dependent insulin-releasing polypeptide concentrations (r = 0.49, P < 0.0001). Among beta-cell function parameters, only insulin secretion at 5 mM glucose from MT correlated inversely with insulin sensitivity (24-h MT: r = -0.74, P < 0.001; 2-h MT: r = -0.52, P < 0.05), whereas the dose-response slope and the OGTT parameters did not. In nine other subjects, reproducibility of model parameters was evaluated from repeated MTs. Coefficients of variation were generally approximately 20%, but the derivative component was less reproducible. We conclude that our model for the multiple MT yields useful information on beta-cell function, particularly with regard to the role of potentiation. With cautious interpretation, a 2-h MT or a standard OGTT can be used as surrogates of 24-h tests in assessing spontaneous beta-cell function.
我们对17名正常志愿者的β细胞功能及其与胰岛素敏感性的关系进行了研究。对于胰岛素分泌（通过C肽反卷积推导得出），将一个数学模型应用于24小时三餐试验（MT）以及口服葡萄糖耐量试验（OGTT）；通过正常血糖胰岛素钳夹技术评估胰岛素敏感性。β细胞模型的特点包括葡萄糖浓度-胰岛素分泌剂量反应（以5 mM葡萄糖时的分泌量和斜率为特征）、与葡萄糖浓度导数成比例的分泌成分以及一个时间依赖性增强因子（调节剂量反应并解释持续高血糖和肠促胰岛素的作用）。从整个24小时MT、MT的前2小时以及OGTT估计出的β细胞剂量反应函数存在系统性差异，因为涉及不同的增强因子。实际上，进餐期间的增强作用高于平均水平（第一餐时为1.6±0.1倍），并且在MT和OGTT中的时间进程不同。然而，如果考虑到增强作用，24小时和2小时MT以及OGTT产生相似的剂量反应，并且大多数β细胞功能参数相互关联（r = 0.50 - 0.86，P≤0.05）。发现增强因子与血浆葡萄糖依赖性胰岛素释放多肽浓度相关（r = 0.49，P < 0.0001）。在β细胞功能参数中，只有MT中5 mM葡萄糖时的胰岛素分泌与胰岛素敏感性呈负相关（24小时MT：r = -0.74，P < 0.001；2小时MT：r = -0.52，P < 0.05），而剂量反应斜率和OGTT参数则不然。在另外九名受试者中，通过重复MT评估了模型参数的可重复性。变异系数一般约为20%，但导数成分的可重复性较差。我们得出结论，我们的多餐试验模型可提供有关β细胞功能的有用信息，特别是关于增强作用的作用。经过谨慎解释，2小时MT或标准OGTT可在评估自发性β细胞功能时用作24小时试验的替代方法。
