Closed Loop Control of a Nonlinear Glucose-Insulin Regulatory System Considering Practical Delays

 

The blood glucose level of a normal human being is within the range of 70-120mg/dl. In diabetic patients, the glucose levels are high due to improper functioning of the pancreas. It is necessary to maintain the plasma glucose concentration in the diabetic patient within the normal range by injecting an appropriate amount of insulin. The plasma glucose is typically measured using a glucose sensor. A model based control strategy needs to be implemented to determine the amount of insulin to be injected to the patient.

 

In this work, a mathematical model representing ultradian oscillatory nature of the glucose and insulin secretions in a normal human being is considered. This model includes various physiological delays resulting in a set of delay differential equations. The model was modified to consider the effects of hyperglycemia, external glucose sensor characteristics and injected insulin kinetics to make it resemble the glucose-insulin regulatory system in the diabetic patients. A delay approximation method was applied for the delay terms in the model and a set of ordinary differential equations were formed. An observer was designed and implemented to measure the state estimates of the model. An extended Kalman filter was implemented to estimate the state variables. These state estimates were then used in the control algorithm. A sensitivity analysis of the parameters in the model was also carried out. The continuous closed loop control algorithm calculates the amount of insulin to be injected to the patient to maintain the blood glucose levels within the normal range. A model predictive control algorithm with constraints was implemented to measure the rate at which the insulin should be injected. This value is then fed to the infusion pump and the drug is delivered accordingly. Thus, the control strategy implemented in this work can be considered as a step towards the development of an artificial pancreas.