A Novel Mathematical Model Detecting Early Individual Changes of Insulin Resistance

Abstract Background: Insulin resistance (IR) and hyperinsulinemia as well as obesity play a key role in the metabolic syndrome (MetS), type 2 diabetes (T2D), and associated cardiovascular disease. Unfortunately, IR and hyperinsulinemia are often diagnosed late (i.e., when the MetS is already clinically evident). An earlier diagnosis of IR would be desirable to reduce its clinical consequences, in particular in view of the increasing prevalence of obesity and diabetes conditions. For this purpose, we developed a mathematical model capable of detecting early onset of IR through small variations of insulin sensitivity, glucose effectiveness, and first- or second-phase responses. Materials and Methods: Murine models provide controlled conditions to study various stages of IR. Various degrees of hypercholesterolemia, obesity, IR, and atherosclerosis were induced in low-density lipoprotein receptor-deficient mice by feeding them cholesterol- or sucrose-rich diets. IR was assessed by oral glucose tolerance tests...