Ng Eric, Kaufman Jaycee M, van Veen Lennaert, Fossat Yan
Ontario Tech University, Oshawa, Ontario, Canada.
Klick Applied Sciences, Toronto, Ontario, Canada.
PLOS Digit Health. 2022 Jul 14;1(7):e0000072. doi: 10.1371/journal.pdig.0000072. eCollection 2022 Jul.
The mathematical modelling of biological systems has historically followed one of two approaches: comprehensive and minimal. In comprehensive models, the involved biological pathways are modelled independently, then brought together as an ensemble of equations that represents the system being studied, most often in the form of a large system of coupled differential equations. This approach often contains a very large number of tuneable parameters (> 100) where each describes some physical or biochemical subproperty. As a result, such models scale very poorly when assimilation of real world data is needed. Furthermore, condensing model results into simple indicators is challenging, an important difficulty in scenarios where medical diagnosis is required. In this paper, we develop a minimal model of glucose homeostasis with the potential to yield diagnostics for pre-diabetes. We model glucose homeostasis as a closed control system containing a self-feedback mechanism that describes the collective effects of the physiological components involved. The model is analyzed as a planar dynamical system, then tested and verified using data collected with continuous glucose monitors (CGMs) from healthy individuals in four separate studies. We show that, although the model has only a small number (3) of tunable parameters, their distributions are consistent across subjects and studies both for hyperglycemic and for hypoglycemic episodes.
全面建模和简约建模。在全面模型中,所涉及的生物途径被独立建模,然后作为一组方程组合在一起,这些方程代表了所研究的系统,通常以大型耦合微分方程组的形式呈现。这种方法通常包含大量(>100个)可调节参数,每个参数描述一些物理或生化子特性。因此,当需要同化现实世界数据时,此类模型的扩展性非常差。此外,将模型结果浓缩为简单指标具有挑战性,这在需要医学诊断的情况下是一个重要难题。在本文中,我们开发了一个葡萄糖稳态的简约模型,该模型有潜力为糖尿病前期提供诊断。我们将葡萄糖稳态建模为一个包含自反馈机制的封闭控制系统,该机制描述了所涉及生理成分的集体效应。该模型作为平面动力系统进行分析,然后使用在四项独立研究中从健康个体收集的连续血糖监测仪(CGM)数据进行测试和验证。我们表明,尽管该模型只有少量(3个)可调节参数,但它们的分布在高血糖和低血糖发作的受试者和研究中都是一致的。