Insulin Resistance and the Metabolic Syndrome severity – a mathematical model

Abstract

Excessive fructose consumption was shown to have deleterious effects on the cardiovascular system, particularly as the metabolic syndrome. However, the degree by which alteration of each pathophysiological factor contributes to the morbidity associated with fructose consumption is not yet clear. We have developed a mathematical model to integrate and uniformly quantify pathophysiological features of the metabolic syndrome on a high fructose-fed dog model. A novel comprehensive measure for the syndrome severity (the “patholog”) and a more intuitive measure of the insulin resistance are introduced. Alteration of hemodynamics, echocardiography and blood chemistry were determined in adult male mongrel dogs fed with 60% isocaloric fructose or normal chow for 7 weeks. The diverse experimental data were transformed into comparable scores and a pre-Hilbert space of states constructed. In such a space one can quantify the severity of any combination of pathophysiological and genomic features and determine the global recovery resulting from a treatment. The model indicates increase of insulin resistance (new index proposed), systolic blood pressure, low-to-high density lipids ratio and angiotensin II as the major contributors to the excessive fructose morbidity. Our model provides the simplest, yet the most intuitive and comprehensive way to integrate data of a wide diversity in visualizing and quantifying a cardiovascular disease