Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 751 23, Uppsala, Sweden.
Department of Pharmacy Practice, Helwan University, Cairo, Egypt.
Pharm Res. 2019 Apr 17;36(6):86. doi: 10.1007/s11095-019-2592-9.
For some biological systems, there exist several models with somewhat different features and perspectives. We propose an evaluation method for NLME models by analyzing real and simulated data from the model of main interest using a structurally different, but similar, NLME model. We showcase this method using the Integrated Glucose Insulin (IGI) model and the Integrated Minimal Model (IMM). Additionally, we try to map parameters carrying similar information between the two models.
A bootstrap of real data and simulated datasets from both the IMM and IGI models were analyzed with the two models. Important parameters of the IMM were mapped to IGI parameters using a large IMM simulated dataset analyzed under the IGI model.
Comparison of the parameters estimated from real data and data simulated with the IMM and analyzed with the IGI model demonstrated differences between real and IMM-simulated data. Comparison of the parameters estimated from real data and data simulated with the IGI model and analyzed with the IMM also demonstrated differences but to a lower extent. The strongest parameter correlations were found for: insulin-dependent glucose clearance (IGI) ~ insulin sensitivity (IMM); insulin-independent glucose clearance (IGI) ~ glucose effectiveness (IMM); and insulin effect parameter (IGI) ~ insulin action (IMM).
We demonstrated a new approach to investigate models' ability to simulate real-life-like data, and the information captured in each model in comparison to real data, and the IMM clinically used parameters were successfully mapped to their corresponding IGI parameters.
对于某些生物学系统,存在一些具有略微不同特征和视角的模型。我们提出了一种通过使用结构上不同但相似的 NLME 模型来分析来自感兴趣模型的真实和模拟数据来评估 NLME 模型的方法。我们使用综合葡萄糖胰岛素 (IGI) 模型和综合最小模型 (IMM) 展示了这种方法。此外,我们试图在两个模型之间映射具有相似信息的参数。
使用真实数据和来自 IMM 和 IGI 模型的模拟数据集的自举分析了两个模型。使用在 IGI 模型下分析的大型 IMM 模拟数据集将 IMM 的重要参数映射到 IGI 参数。
从真实数据和 IMM 模拟数据并使用 IGI 模型进行分析中估计的参数的比较表明了真实数据和 IMM 模拟数据之间的差异。从真实数据和使用 IGI 模型模拟的数据并使用 IMM 进行分析中估计的参数的比较也表明了差异,但程度较低。发现最强的参数相关性如下:胰岛素依赖性葡萄糖清除率 (IGI)胰岛素敏感性 (IMM);胰岛素非依赖性葡萄糖清除率 (IGI)葡萄糖效应 (IMM);和胰岛素效应参数 (IGI)~胰岛素作用 (IMM)。
我们展示了一种新方法来研究模型模拟真实数据的能力,以及每个模型与真实数据相比所捕获的信息,并且成功地将临床使用的 IMM 参数映射到其相应的 IGI 参数。