Holistic multilevel modeling of type‐2 diabetes (1180.5)

Abstract

Type‐2 diabetes (T2D), is presenting a rapidly growing health and economic problem. For personalized lifestyle/medical treatment advice, it is essential that computer modelling tools become available to integrate the results from diagnostic tools that probe the function of all involved organs/processes in a single holistic view. Our objective is to build such a model for T2D, an important comorbidity of metabolic syndrome.As a first step towards fully personalized quantitative diagnosis and prediction we developed a descriptive model based on causal loop diagrams at a very high aggregation level that integrates mechanisms across all relevant domains including body weight dynamics, glucose/insulin dynamics, inflammation, gut health, and mental stress. The model integrates qualitative and semi‐quantitative information and expert knowledge.The model was able to simulate the development of T2D over a multi‐year period following different food intake profiles, as well as disease modulation by increased physical activity or mental stress‐relieving lifestyles.In a recently started EU project MISSION‐T2D (www.mission‐t2d.eu), the high aggregation level model will be interlinked with a model at a second aggregation level that describes the integrated dynamics of all processes at the minute‐day timescale. This allows to enrich the model with mechanisms probed by PK‐PD studies and nutritional challenge tests and should pave the way for translating validated multilevel immune‐metabolic models into the clinical setting of T2D.Concluding, we have successfully made a first step towards a multiorgan, multilevel systems health model of T2D that can be used to integrate diagnostic data from different domains for personalized lifestyle/treatment advice.