Digital twin predicting diet response before and after long-term fasting

被引:7
作者
Silfvergren, Oscar [1 ]
Simonsson, Christian [1 ,2 ]
Ekstedt, Mattias [2 ,3 ]
Lundberg, Peter [2 ,3 ,4 ]
Gennemark, Peter [1 ,5 ]
Cedersund, Gunnar [1 ,2 ]
机构
[1] Linkoping Univ, Dept Biomed Engn, IMT, Linkoping, Sweden
[2] Linkoping Univ, Ctr Med Image Sci & Visualisat, Linkoping, Sweden
[3] Linkoping Univ, Dept Hlth Med & Caring Sci, Linkoping, Sweden
[4] Linkoping Univ, Dept Med Radiat Phys, Linkoping, Sweden
[5] AstraZeneca, Drug Metab & Pharmacokinet, Res & Early Dev, Cardiovasc Renal & Metab CVRM,BioPharmaceut R&D, Gothenburg, Sweden
基金
欧盟地平线“2020”; 瑞典研究理事会;
关键词
DIABETES-MELLITUS; GLUCOSE-HOMEOSTASIS; INSULIN SENSITIVITY; HIGH-CARBOHYDRATE; SYSTEMS BIOLOGY; OBESE-PATIENTS; MINIMAL MODEL; RISK; GLUCONEOGENESIS; HYPERGLYCEMIA;
D O I
10.1371/journal.pcbi.1010469
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Today, there is great interest in diets proposing new combinations of macronutrient compositions and fasting schedules. Unfortunately, there is little consensus regarding the impact of these different diets, since available studies measure different sets of variables in different populations, thus only providing partial, non-connected insights. We lack an approach for integrating all such partial insights into a useful and interconnected big picture. Herein, we present such an integrating tool. The tool uses a novel mathematical model that describes mechanisms regulating diet response and fasting metabolic fluxes, both for organ-organ crosstalk, and inside the liver. The tool can mechanistically explain and integrate data from several clinical studies, and correctly predict new independent data, including data from a new study. Using this model, we can predict non-measured variables, e.g. hepatic glycogen and gluconeogenesis, in response to fasting and different diets. Furthermore, we exemplify how such metabolic responses can be successfully adapted to a specific individual's sex, weight, height, as well as to the individual's historical data on metabolite dynamics. This tool enables an offline digital twin technology.
引用
收藏
页数:26
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