Optimal regulation of blood glucose level in Type I diabetes using insulin and glucagon

PLoS One. 2019 Mar 20;14(3):e0213665. doi: 10.1371/journal.pone.0213665. eCollection 2019.

Abstract

The Glucose-Insulin-Glucagon nonlinear model accurately describes how the body responds to exogenously supplied insulin and glucagon in patients affected by Type I diabetes. Based on this model, we design infusion rates of either insulin (monotherapy) or insulin and glucagon (dual therapy) that can optimally maintain the blood glucose level within desired limits after consumption of a meal and prevent the onset of both hypoglycemia and hyperglycemia. This problem is formulated as a nonlinear optimal control problem, which we solve using the numerical optimal control package [Formula: see text]. Interestingly, in the case of monotherapy, we find the optimal solution is close to the standard method of insulin based glucose regulation, which is to assume a variable amount of insulin half an hour before each meal. We also find that the optimal dual therapy (that uses both insulin and glucagon) is better able to regulate glucose as compared to using insulin alone. We also propose an ad-hoc rule for both the dosage and the time of delivery of insulin and glucagon.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Blood Glucose / analysis*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Delivery Systems
  • Glucagon / therapeutic use*
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / prevention & control
  • Hypoglycemia / blood
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use*
  • Insulin Infusion Systems
  • Nonlinear Dynamics
  • Postprandial Period
  • Risk

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Glucagon

Grants and funding

A.S, I.K. and F.S. are supported by the National Science Foundation (https://www.nsf.gov/funding/pgm_summ.jsp?pims_id=505277) grant CRISP-1541148. F.D.R. is supported by the National Science Foundation (https://www.nsf.gov/div/index.jsp?div=CMMI) grants CMMI- 1400193 and CMMI-1727948. All four of us are also supported by the Office of Naval Research (https://www.onr.navy.mil/en/Contracts-Grants/Funding-Opportunities/Broad-Agency-Announcements) grant N00014-16-1-2637, and the Defense Threat Reduction Agency (http://www.dtra.mil/Research/Basic-and-Applied-Science/Research-Funding-Opportunities/) grant HDTRA1-12-1-0020.