用于双激素血糖控制器计算机模拟测试的胰高血糖素-葡萄糖动力学复合模型。
A composite model of glucagon-glucose dynamics for in silico testing of bihormonal glucose controllers.
作者信息
Herrero Pau, Georgiou Pantelis, Oliver Nick, Reddy Monika, Johnston Desmond, Toumazou Christofer
机构信息
Center for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Institute of Biomedical Engineering, Imperial College London, South Kensington Campus, London, UK.
出版信息
J Diabetes Sci Technol. 2013 Jul 1;7(4):941-51. doi: 10.1177/193229681300700416.
BACKGROUND
The utility of simulation environments in the development of an artificial pancreas for type 1 diabetes mellitus (T1DM) management is well established. The availability of a simulator that incorporates glucagon as a counterregulatory hormone to insulin would allow more efficient design of bihormonal glucose controllers. Existing models of the glucose regulatory system that incorporates glucagon action are difficult to identify without using tracer data. In this article, we present a novel model of glucagon-glucose dynamics that can be easily identified with standard clinical research data.
METHODS
The minimal model of plasma glucose and insulin kinetics was extended to account for the action of glucagon on net endogenous glucose production by incorporating a new compartment. An existing subcutaneous insulin absorption model was used to account for subcutaneous insulin delivery. The same model of insulin pharmacokinetics was employed to model the pharmacokinetics of subcutaneous glucagon absorption. Finally, we incorporated an existing gastrointestinal absorption model to account for meal intake. Data from a closed-loop artificial pancreas study using a bihormonal controller on T1DM subjects were employed to identify the composite model. To test the validity of the proposed model, a bihormonal controller was designed using the identified model.
RESULTS
Model parameters were identified with good precision, and an excellent fitting of the model with the experimental data was achieved. The proposed model allowed the design of a bihormonal controller and demonstrated its ability to improve glycemic control over a single-hormone controller.
CONCLUSIONS
A novel composite model, which can be easily identified with standard clinical data, is able to account for the effect of exogenous insulin and glucagon infusion on glucose dynamics. This model represents another step toward the development of a bihormonal artificial pancreas.
背景
模拟环境在1型糖尿病（T1DM）管理的人工胰腺开发中的效用已得到充分证实。若有一个将胰高血糖素作为胰岛素反调节激素纳入的模拟器，将能更高效地设计双激素葡萄糖控制器。现有的包含胰高血糖素作用的葡萄糖调节系统模型，若不使用示踪数据则难以识别。在本文中，我们提出了一种新的胰高血糖素 - 葡萄糖动力学模型，该模型可通过标准临床研究数据轻松识别。
方法
通过纳入一个新的隔室，扩展了血浆葡萄糖和胰岛素动力学的最小模型，以解释胰高血糖素对净内源性葡萄糖生成的作用。使用现有的皮下胰岛素吸收模型来解释皮下胰岛素递送。采用相同的胰岛素药代动力学模型来模拟皮下胰高血糖素吸收的药代动力学。最后，我们纳入了现有的胃肠吸收模型来解释进餐摄入。使用双激素控制器对T1DM受试者进行闭环人工胰腺研究的数据来识别复合模型。为了测试所提出模型的有效性，使用识别出的模型设计了一种双激素控制器。
结果
模型参数被精确识别，并且模型与实验数据实现了极佳的拟合。所提出的模型允许设计双激素控制器，并证明了其比单激素控制器更能改善血糖控制的能力。
结论
一种能够通过标准临床数据轻松识别的新型复合模型，能够解释外源性胰岛素和胰高血糖素输注对葡萄糖动力学的影响。该模型代表了双激素人工胰腺开发的又一步进展。
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