Comput Methods Programs Biomed - Identification of an integrated mathematical model of standard oral glucose tolerance test for characterization of insulin potentiation in health.

Tópicos

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Resumo

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.

Resumo Limpo

two new formul respect denomin intm intm integr mathemat model describ glycem insulinem respons g oral glucos toler test ogtt propos compar intm assum singl compart intestin deriv power exponenti function gastric empti rate intm nonlinear threecompart system model adopt produc realist multiphas gastric empti rate model implement matlabbas twostep procedur estim seven adjust coeffici character gastric empti rate incretin insulin glucos kinet model behaviour test vs mean plasma glucagonlik peptid glp glucosedepend insulinotrop polypeptid gip glucos insulin measur two differ laboratori glycem profil observ g ogtt match healthi subject hc hcgroup respect mean isoglycem intraven glucos iivg infus hypothesi addit effect glp gip insulin potenti result demonstr substanti equival two model match data model paramet estim show suitabl marker differ observ ogtt match iivg respons hcgroup compar hcgroup model implement twostep paramet estim procedur enhanc possibl prospect applic individu incretin effect singl subject hisher data plug

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