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

IEEE Trans Biomed Eng. 2022 Mar;69(3):1273-1280. doi: 10.1109/TBME.2021.3125839. Epub 2022 Feb 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Diabetes Mellitus, Type 1* / drug therapy
  • Disease Models, Animal
  • Glucagon
  • Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Infusion Systems
  • Pancreas, Artificial*
  • Swine

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Glucagon
  • Glucose