Nonlinear Modeling of the Dynamic Effects of Infused Insulin on Glucose: Comparison of Compartmental With Volterra Models

This paper presents the results of a computational study that compares simulated compartmental (differential equation) and Volterra models of the dynamic effects of insulin on blood glucose concentration in humans. In the first approach, we employ the widely accepted ldquominimal modelrdquo and an augmented form of it, which incorporates the effect of insulin secretion by the pancreas, in order to represent the actual closed-loop operating conditions of the system, and in the second modeling approach, we employ the general class of Volterra-type models that are estimated from input-output data. We demonstrate both the equivalence between the two approaches analytically and the feasibility of obtaining accurate Volterra models from insulin-glucose data generated from the compartmental models. The results corroborate the proposition that it may be preferable to obtain data-driven (i.e., inductive) models in a more general and realistic operating context, without resorting to the restrictive prior assumptions and simplifications regarding model structure and/or experimental protocols (e.g., glucose tolerance tests) that are necessary for the compartmental models proposed previously. These prior assumptions may lead to results that are improperly constrained or biased by preconceived (and possibly erroneous) notions-a risk that is avoided when we let the data guide the inductive selection of the appropriate model within the general class of Volterra-type models, as our simulation results suggest.