论文标题
葡萄糖动力学的低阶非线性动物模型,用于腹膜腹膜内人造胰腺
Low-Order Nonlinear Animal Model of Glucose Dynamics for a Bihormonal Intraperitoneal Artificial Pancreas
论文作者
论文摘要
目的:人工胰腺(AP)的设计以调节血糖水平需要可靠的控制方法。模型预测控制已成为血糖控制的有前途的方法。但是,基于模型的控制方法需要计算简单且可识别的数学模型,这些模型准确地代表了葡萄糖动力学,这由于葡萄糖稳态的复杂性而具有挑战性。方法:在这项工作中,提出了一个简单的模型,以估计1型糖尿病(T1DM)受试者中的血糖浓度。该模型中的新特征是用于腹膜内胰岛素吸收和单独的胰高血糖素敏感性状态的动力学动力学。进行了曲线可能性和基于灵敏度矩阵的单数值分解的方法,以评估参数可识别性,并指导降低模型以改善参数的识别。结果:获得并校准了10个参数的还原模型,显示出与胰岛素和胰高血糖素大体在腹膜内腔中递送的猪的实验数据的良好拟合。结论:具有幂律动力学的简单模型可以准确地代表提交给腹膜内胰岛素和胰高血糖素注射的葡萄糖动力学。发现还原模型显示出局部实用和结构可识别性。重要性:提出的模型促进了腹膜内双激素模型在动物试验中的闭环控制。
Objective: The design of an Artificial Pancreas (AP) to regulate blood glucose levels requires reliable control methods. Model Predictive Control has emerged as a promising approach for glycemia control. However, model--based control methods require computationally simple and identifiable mathematical models that represent glucose dynamics accurately, which is challenging due to the complexity of glucose homeostasis. Methods: In this work, a simple model is deduced to estimate blood glucose concentration in subjects with Type 1 Diabetes Mellitus (T1DM). Novel features in the model are power--law kinetics for intraperitoneal insulin absorption and a separate glucagon sensitivity state. Profile likelihood and a method based on singular value decomposition of the sensitivity matrix are carried out to assess parameter identifiability and guide a model reduction for improving the identification of parameters. Results: A reduced model with 10 parameters is obtained and calibrated, showing good fit to experimental data from pigs where insulin and glucagon boluses were delivered in the intraperitoneal cavity. Conclusion: A simple model with power--law kinetics can accurately represent glucose dynamics submitted to intraperitoneal insulin and glucagon injections. The reduced model was found to exhibit local practical as well as structural identifiability. Importance: The proposed model facilitates intraperitoneal bi-hormonal model-based closed-loop control in animal trials.