Safety constraints in an artificial pancreatic beta cell: an implementation of model predictive control with insulin on board.
BACKGROUND
Type 1 diabetes mellitus (T1DM) is characterized by the destruction of pancreatic beta cells, resulting in the inability to produce sufficient insulin to maintain normoglycemia. As a result, people with T1DM depend on exogenous insulin that is given either by multiple daily injections or by an insulin pump to control their blood glucose. A challenging task is to design the next step in T1DM therapy: a fully automated insulin delivery system consisting of an artificial pancreatic beta cell that shall provide both safe and effective therapy. The core of such a system is a control algorithm that calculates the insulin dose based on automated glucose measurements.


METHODS
A model predictive control (MPC) algorithm was designed to control glycemia by controlling exogenous insulin delivery. The MPC algorithm contained a dynamic safety constraint, insulin on board (IOB), which incorporated the clinical values of correction factor and insulin-to-carbohydrate ratio along with estimated insulin action decay curves as part of the optimal control solution.


RESULTS
The results emphasized the ability of the IOB constraint to significantly improve the glucose/insulin control trajectories in the presence of aggressive control actions. The simulation results indicated that 50% of the simulations conducted without the IOB constraint resulted in hypoglycemic events, compared to 10% of the simulations that included the IOB constraint.


CONCLUSIONS
Achieving both efficacy and safety in an artificial pancreatic beta cell calls for an IOB safety constraint that is able to override aggressive control moves (large insulin doses), thereby minimizing the risk of hypoglycemia.
Ellingsen
Christian
C
Department of Chemical Engineering, University of California at Santa Barbara, Santa Barbara, CA 93106-5080, USA.
Dassau
Eyal
E
Zisser
Howard
H
Grosman
Benyamin
B
Percival
Matthew W
MW
Jovanovic
Lois
L
Doyle
Francis J
FJ
D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis; D002241:Carbohydrates / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007332:Insulin Infusion Systems / Q000009:adverse effects*; D008962:Models, Theoretical; D016896:Treatment Outcome
D001786:Blood Glucose; D002241:Carbohydrates; D007328:Insulin