Identifiability Analysis of Three Control-Oriented Models for Use in Artificial Pancreas Systems

Abstract

Objective: Our aim is to analyze the identifiability of three commonly used control-oriented models for glucose control in patients with type 1 diabetes (T1D). Methods: Structural and practical identifiability analysis were performed on three published control-oriented models for glucose control in patients with type 1 diabetes (T1D): the subcutaneous oral glucose minimal model (SOGMM), the intensive control insulin-nutrition-glucose (ICING) model, and the minimal model control-oriented (MMC). Structural identifiability was addressed with a combination of the generating series (GS) approach and identifiability tableaus whereas practical identifiability was studied by means of (1) global ranking of parameters via sensitivity analysis together with the Latin hypercube sampling method (LHS) and (2) collinearity analysis among parameters. For practical identifiability and model identification, continuous glucose monitor (CGM), insulin pump, and meal records were selected from a set of patients (n = 5) on continuous subcutaneous insulin infusion (CSII) that underwent a clinical trial in an outpatient setting. The performance of the identified models was analyzed by means of the root mean square (RMS) criterion. Results: A reliable set of identifiable parameters was found for every studied model after analyzing the possible identifiability issues of the original parameter sets. According to an importance factor ([Formula: see text]), it was shown that insulin sensitivity is not the most influential parameter from the dynamical point of view, that is, is not the parameter impacting the outputs the most of the three models, contrary to what is assumed in the literature. For the test data, the models demonstrated similar performance with most RMS values around 20 mg/dl (min: 15.64 mg/dl, max: 51.32 mg/dl). However, MMC failed to identify the model for patient 4. Also, considering the three models, the MMC model showed the higher parameter variability when reidentified every 6 hours. Conclusion: This study shows that both structural and practical identifiability analysis need to be considered prior to the model identification/individualization in patients with T1D. It was shown that all the studied models are able to represent the CGM data, yet their usefulness in a hypothetical artificial pancreas could be a matter of debate. In spite that the three models do not capture all the dynamics and metabolic effects as a maximal model (ie, our FDA-accepted UVa/Padova simulator), SOGMM and ICING appear to be more appealing than MMC regarding both the performance and parameter variability after reidentification. Although the model predictions of ICING are comparable to the ones of the SOGMM model, the large parameter set makes the model prone to overfitting if all parameters are identified. Moreover, the existence of a high nonlinear function like [Formula: see text] prevents the use of tools from the linear systems theory.