Closed-loop control scheme for the Euglycemic Hyperinsulinemic Clamp: Validation on virtual patients

A closed-loop control scheme is here investigated, for the Euglycemic Hyperinsulinemic Clamp (EHC), the gold standard experiment to estimate the individual insulin sensitivity. During the EHC large amounts of insulin are administered intra-venously to the subject, and plasma glycemia is maintained at a normal, baseline level by means of an exogenous glucose infusion, according to established protocols. Based on a Delay Differential Equation (DDE) model of the glucose-insulin system, a closed-loop control has been recently proposed by the same authors showing that, in way of principle, it is possible to design an observer-based control law for the exogenous glucose profile, by solely exploiting real-time plasma glucose measurements. This note further investigates the closed-loop control scheme in order to validate it in spite of the many sources of uncertainties and malfunctioning that inevitably arise. The main feature is to close the feedback onto a different, large-scale multi-compartmental model (standing for a Virtual Patient, VP), instead of the small-scale, DDE model adopted to design the control law. The chosen large-scale model for the VP has been recently accepted by the Food and Drug Administration as a substitute to animal trials for the preclinical testing of control strategies in artificial pancreas. A benchmark based on a population of heterogeneous virtual patients has been implemented and the very good results show the robustness of the proposed methodology.