O'Donovan Shauna D, Erdős Balázs, Jacobs Doris M, Wanders Anne J, Thomas E Louise, Bell Jimmy D, Rundle Milena, Frost Gary, Arts Ilja C W, Afman Lydia A, van Riel Natal A W
Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
iScience. 2022 Oct 3;25(11):105206. doi: 10.1016/j.isci.2022.105206. eCollection 2022 Nov 18.
Despite the pivotal role played by elevated circulating triglyceride levels in the pathophysiology of cardio-metabolic diseases many of the indices used to quantify metabolic health focus on deviations in glucose and insulin alone. We present the Mixed Meal Model, a computational model describing the systemic interplay between triglycerides, free fatty acids, glucose, and insulin. We show that the Mixed Meal Model can capture deviations in the post-meal excursions of plasma glucose, insulin, and triglyceride that are indicative of features of metabolic resilience; quantifying insulin resistance and liver fat; validated by comparison to gold-standard measures. We also demonstrate that the Mixed Meal Model is generalizable, applying it to meals with diverse macro-nutrient compositions. In this way, by coupling triglycerides to the glucose-insulin system the Mixed Meal Model provides a more holistic assessment of metabolic resilience from meal response data, quantifying pre-clinical metabolic deteriorations that drive disease development in overweight and obesity.
尽管循环甘油三酯水平升高在心脏代谢疾病的病理生理学中起着关键作用，但许多用于量化代谢健康的指标仅关注葡萄糖和胰岛素的偏差。我们提出了混合餐模型，这是一个描述甘油三酯、游离脂肪酸、葡萄糖和胰岛素之间系统相互作用的计算模型。我们表明，混合餐模型可以捕捉血浆葡萄糖、胰岛素和甘油三酯餐后波动的偏差，这些偏差表明代谢弹性的特征；量化胰岛素抵抗和肝脏脂肪；通过与金标准测量方法比较进行验证。我们还证明了混合餐模型具有通用性，将其应用于具有不同宏量营养素组成的餐食。通过这种方式，通过将甘油三酯与葡萄糖 - 胰岛素系统耦合，混合餐模型从餐食反应数据中提供了对代谢弹性更全面的评估，量化了导致超重和肥胖中疾病发展的临床前代谢恶化。
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