Duun-Henriksen Anne Katrine, Schmidt Signe, Røge Rikke Meldgaard, Møller Jonas Bech, Nørgaard Kirsten, Jørgensen John Bagterp, Madsen Henrik
DTU Compute, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Matematiktorvet, Building 303b, 2800 Lyngby, Denmark.
J Diabetes Sci Technol. 2013 Mar 1;7(2):431-40. doi: 10.1177/193229681300700220.
The acceptance of virtual preclinical testing of control algorithms is growing and thus also the need for robust and reliable models. Models based on ordinary differential equations (ODEs) can rarely be validated with standard statistical tools. Stochastic differential equations (SDEs) offer the possibility of building models that can be validated statistically and that are capable of predicting not only a realistic trajectory, but also the uncertainty of the prediction. In an SDE, the prediction error is split into two noise terms. This separation ensures that the errors are uncorrelated and provides the possibility to pinpoint model deficiencies.
An identifiable model of the glucoregulatory system in a type 1 diabetes mellitus (T1DM) patient is used as the basis for development of a stochastic-differential-equation-based grey-box model (SDE-GB). The parameters are estimated on clinical data from four T1DM patients. The optimal SDE-GB is determined from likelihood-ratio tests. Finally, parameter tracking is used to track the variation in the "time to peak of meal response" parameter.
We found that the transformation of the ODE model into an SDE-GB resulted in a significant improvement in the prediction and uncorrelated errors. Tracking of the "peak time of meal absorption" parameter showed that the absorption rate varied according to meal type.
This study shows the potential of using SDE-GBs in diabetes modeling. Improved model predictions were obtained due to the separation of the prediction error. SDE-GBs offer a solid framework for using statistical tools for model validation and model development.
控制算法的虚拟临床前测试的认可度不断提高,因此对强大且可靠的模型的需求也在增加。基于常微分方程(ODE)的模型很少能用标准统计工具进行验证。随机微分方程(SDE)提供了构建能够进行统计验证的模型的可能性,这些模型不仅能够预测现实的轨迹,还能预测预测的不确定性。在一个SDE中,预测误差被分解为两个噪声项。这种分离确保了误差是不相关的,并提供了查明模型缺陷的可能性。
将一名1型糖尿病(T1DM)患者的葡萄糖调节系统的可识别模型用作基于随机微分方程的灰箱模型(SDE-GB)开发的基础。根据四名T1DM患者的临床数据估计参数。通过似然比检验确定最优的SDE-GB。最后,使用参数跟踪来跟踪“进餐反应峰值时间”参数的变化。
我们发现将ODE模型转换为SDE-GB导致预测和不相关误差有显著改善。对“进餐吸收峰值时间”参数的跟踪表明,吸收速率根据进餐类型而变化。
本研究显示了在糖尿病建模中使用SDE-GB的潜力。由于预测误差的分离,获得了改进的模型预测。SDE-GB为使用统计工具进行模型验证和模型开发提供了一个坚实的框架。