Adaptive Zone Model Predictive Control of Artificial Pancreas Based on Glucose- and Velocity-Dependent Control Penalties

Objective: Zone model predictive control (MPC) has been proven to be an efficient approach to closed-loop insulin delivery in clinical studies. In this paper, we aim to safely reduce mean glucose levels by proposing control penalty adaptation in the cost function of zone MPC. Methods: A zone MPC method with a dynamic cost function that updates its control penalty parameters in real time according to the predicted glucose and its rate of change is developed. The proposed method is evaluated on the entire 100-adult cohort of the FDA-accepted UVA/Padova T1DM simulator and compared with the zone MPC tested in an extended outpatient study. Results: For unannounced meals, the proposed method leads to statistically significant improvements in terms of mean glucose (153.8 mg/dL vs. 159.0 mg/dL; $\boldsymbol p ) and percentage time in $[70, 180]$ mg/dL ( $\text{70.5}\%$ vs. $\text{66.3}\%$ ; $\boldsymbol p ) without increasing the risk of hypoglycemia. Performance for announced meals is similar to that obtained without adaptation. The proposed method also behaves properly and safely for scenarios of moderate meal-bolus and basal rate mismatches, as well as simulated unannounced exercise. Advisory-mode analysis based on clinical data indicates that the method can reduce glucose levels through suggesting additional safe amounts of insulin on top of those suggested by the zone MPC used in the study. Conclusion: The proposed method leads to improved glucose control without increasing hypoglycemia risks. Significance: The results validate the feasibility of improving glucose regulation through glucose- and velocity-dependent control penalty adaptation in MPC design.