Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
J Clin Pharmacol. 2010 Mar;50(3):246-56. doi: 10.1177/0091270009341185. Epub 2009 Nov 25.
The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 healthy volunteers were used. Analysis was based on the previously developed intravenous model with extensions for glucose absorption and incretin effect on insulin secretion. The need for additional structural components was evaluated. The model was evaluated by simulation and a bootstrap. Multiple glucose and insulin concentration peaks were observed in most individuals as well as hypoglycemic episodes in the second half of the experiment. The OGTT data were successfully described by the extended basic model. An additional control mechanism of insulin on glucose production improved the description of the data. The model showed good predictive properties, and parameters were estimated with good precision. In conclusion, a previously presented integrated model has been extended to describe glucose and insulin concentrations in healthy volunteers following an OGTT. The characterization of the differences between the healthy and diabetic stages in the IGI model could potentially be used to extrapolate drug effect from healthy volunteers to T2DM.
将先前开发的用于葡萄糖和胰岛素(IGI)的综合模型扩展到健康志愿者的口服葡萄糖耐量试验(OGTT)中,可能有助于更好地了解健康个体和 2 型糖尿病(T2DM)患者之间的差异。使用了 23 名健康志愿者的 OGTT 数据。分析基于先前开发的静脉内模型,并扩展了葡萄糖吸收和肠促胰岛素对胰岛素分泌的作用。评估了是否需要其他结构组件。通过模拟和引导抽样对模型进行了评估。大多数个体中观察到多次葡萄糖和胰岛素浓度峰值,以及实验后半段出现低血糖发作。扩展的基本模型成功地描述了 OGTT 数据。增加胰岛素对葡萄糖生成的控制机制可改善数据描述。该模型显示出良好的预测性能,并且参数估计具有良好的精度。总之,先前提出的综合模型已扩展用于描述健康志愿者进行 OGTT 后的葡萄糖和胰岛素浓度。IGI 模型中健康和糖尿病阶段之间差异的特征描述,有可能用于将药物作用从健康志愿者外推到 T2DM。