Low-Order Nonlinear Animal Model of Glucose Dynamics for a Bihormonal Intraperitoneal Artificial Pancreas

TL;DR

This paper introduces a simple, identifiable nonlinear model of glucose dynamics with power-law kinetics for intraperitoneal insulin and glucagon, aiding control in bi-hormonal artificial pancreas systems.

Contribution

It develops a low-order, nonlinear model with power-law kinetics and a glucagon sensitivity state, validated with experimental pig data, enhancing model-based control for intraperitoneal glucose regulation.

Findings

Reduced model with 10 parameters fits pig data well

Model exhibits local practical and structural identifiability

Power-law kinetics accurately represent glucose dynamics

Abstract

Objective: The design of an Artificial Pancreas (AP) to regulate blood glucose levels requires reliable control methods. Model Predictive Control has emerged as a promising approach for glycemia control. However, model--based control methods require computationally simple and identifiable mathematical models that represent glucose dynamics accurately, which is challenging due to the complexity of glucose homeostasis. Methods: In this work, a simple model is deduced to estimate blood glucose concentration in subjects with Type 1 Diabetes Mellitus (T1DM). Novel features in the model are power--law kinetics for intraperitoneal insulin absorption and a separate glucagon sensitivity state. Profile likelihood and a method based on singular value decomposition of the sensitivity matrix are carried out to assess parameter identifiability and guide a model reduction for improving the identification of parameters. Results: A reduced model with 10 parameters is obtained and calibrated, showing good fit to experimental data from pigs where insulin and glucagon boluses were delivered in the intraperitoneal cavity. Conclusion: A simple model with power--law kinetics can accurately represent glucose dynamics submitted to intraperitoneal insulin and glucagon injections. The reduced model was found to exhibit local practical as well as structural identifiability. Importance: The proposed model facilitates intraperitoneal bi-hormonal model-based closed-loop control in animal trials.