title: Identification of an integrated mathematical model of standard oral glucose tolerance test for characterization of insulin potentiation in health.
abstract: Two new formulations, respectively denominated INT_M1 and INT_M2, of an integrated mathematical model to describe the glycemic and insulinemic responses to a 75 g oral glucose tolerance test (OGTT) are proposed and compared. The INT_M1 assumes a single compartment for the intestine and the derivative of a power exponential function for the gastric emptying rate, while, in the INT_M2, a nonlinear three-compartment system model is adopted to produce a more realistic, multiphase gastric emptying rate. Both models were implemented in a Matlab-based, two-step procedure for estimation of seven adjustable coefficients characterizing the gastric emptying rate and the incretin, insulin and glucose kinetics. Model behaviour was tested vs. mean plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucose and insulin measurements from two different laboratories, where glycemic profiles observed during a 75 g OGTT were matched in healthy subjects (HC1- and HC2-group, respectively) by means of an isoglycemic intravenous glucose (I-IVG) infusion. Under the hypothesis of an additive effect of GLP-1 and GIP on insulin potentiation, our results demonstrated a substantial equivalence of the two models in matching the data. Model parameter estimates showed to be suitable markers of differences observed in the OGTT and matched I-IVG responses from the HC1-group compared to the HC2-group. Model implementation in our two-step parameter estimation procedure enhances the possibility of a prospective application for individualization of the incretin effect in a single subject, when his/her data are plugged in.
authors.affiliation: Department of Information Engineering, Polytechnic University of Marche, Ancona, Italy. r.burattini@univpm.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Burattini
authors.forename: Micaela
authors.initials: M
authors.lastname: Morettini
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D005947:Glucose / Q000493:pharmacokinetics*; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D008954:Models, Biological; D018511:Systems Integration
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose