In silico diabetology

Abstract

Simulation models can contribute substantially to our understanding and ability to control the dynamic processes underlying impaired glucose metabolism in diabetic patients. The aim of this paper is to outline a new comprehensive, physiologically-based dynamic model of glucose homeostasis incorporating up-to-date quantitative knowledge about glucose metabolism and its control by insulin and glucagon. The model is composed of three submodels for glucose, insulin, and glucagon. The glucose submodel specifies the dynamics of glucose absorption following meals, hepatic glucose production and uptake, peripheral glucose uptake, kidney excretion, and insulin-independent uptake of glucose in the brain and red blood cells. The insulin submodel includes equations for insulin absorption, pancreatic insulin release and insulin clearance. The glucagon model specifies the hormone secretion and elimination kinetics. Algebraic equations are used to specify (i) how the hormones affect glucose production and utilisation in various compartments such as liver, muscle and fat tissues, and (ii) how glucose levels modify insulin and glucagon release from the pancreas. Setting the values of various model parameters is used to generate virtual individual patients. The model allows the simulation of 24-hour blood glucose profiles for both insulin-dependent non-insulin dependent diabetic patients.