Incretin-Induced Insulin Potentiation Characterized by an Improved Mathematical Model of Oral Glucose Tolerance Test

Abstract

A model previously proposed by others to simulate glycemia and insulinemia responses to an oral glucose tolerance test (OGTT), with explicit description of the “incretin effect”, was improved by incorporating a nonlinear three-compartment model for a more realistic description of the gastric emptying rate. Differently from the pre-existing model, which was constrained to 50 and 100 g oral glucose loads, our improved model was built upon a clinically consistent 75 g OGTT. Model implementation in a Matlab-based parametric identification procedure allowed optimization of seven adjustable characteristic coefficients of the incretin, insulin and glucose kinetics, by fitting to data from a previously published study where glycemic profiles observed during an OGTT were matched in a group of healthy subjects by means of an isoglycemic intravenous glucose (I-IVG) infusion. Our results demonstrate that our improved model is a suitable tool to reproduce the incretin-induced insulin potentiation observed by comparing OGTT and matched I-IVG data, and enhance the possibility of a prospective application for individualization of the incretin effect in a single subject, when his/her data are plugged in.