In silico model and sensitivity analysis of plasma glucose regulation: towards an individualized maximal model for physiology and pathophysiology

The present study focuses on metabolic hormone regulation of plasma glucose and its role in type 2 diabetes (T2D). We propose an individualized maximal model based on plasma glucose dynamics in healthy individuals, considering key substrates and hormones after oral intake. The model accurately simulates T2D pathophysiology, including effects of free fatty acids, glucagon, GLP-1, ghrelin and leptin on insulin and glucagon levels. Model simulations closely match clinical data from oral glucose tolerance tests in normal and T2D subjects. However, the model’s complexity poses challenges for parameter estimation. To address this, we conducted a Sobol sensitivity analysis to identify influential parameters and simplify the model while preserving its dynamic interpretation. This approach reveals critical parameters influencing glucose regulation, aiding in understanding model dynamics and improving computational efficiency