A Multi-Scale Immune System Simulator for the Onset of Type 2 Diabetes

Type 2 diabetes mellitus (T2D), the most common form of diabetes, is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and insulin deficiency. Although genetic predisposition determines in part the susceptibility to T2D, an unhealthy diet and a sedentary lifestyle are commonly recognised as essential drivers for the onset of the disease. Indeed, considerable evidence suggests that regular exercise and appropriate nutrition bring undeniable health benefits by reducing the risk of developing T2D or delaying its onset. The literature dealing with mathematical modelling for diabetes is abundant and in the view of a growing more personalized medicine the benefits of having tools to represent different virtual patient populations are clear. In this study, we describe a multi-scale computational model of the human metabolic and inflammatory status that is determined by individual dietary and activity habits. It includes a description of the immune activation and inflammation, a model for the food intake, stomach emptying and gut absorption of all three macronutrients (proteins, carbohydrates, fats), a component to account for the effects of physical activity on the hormones' regulation and the inflammatory state of the individual, and finally, a characterization of energy intake-expenditure balance. All these pieces are merged into a single integrated simulation tool to provide a helpful aid that can be used proactively to prevent the onset of the disease. Moreover, this model turns out to help design virtual cohorts of patients to conduct in silico studies.