Glucose Rate-of-Change and Insulin-on-Board Jointly Weighted Zone Model Predictive Control.

We present design and evaluation of closed-loop insulin delivery using zone model predictive control (MPC) featuring an adaptive weighting scheme to address prolonged hyperglycemia due to changes in insulin sensitivity, underdelivery from profile mismatch, and meal composition. In the MPC cost function, the penalty on predicted glucose deviation from the upper zone boundary is weighted by a function of predicted glucose rate-of-change (ROC) and insulin-on-board (IOB). The asymmetric weighting gradually increases when glucose ROC and IOB were jointly low, independent of glucose magnitude, to limit hyperglycemia while aggressively reduces for negative glucose ROC to avoid hypoglycemia. The proposed controller was evaluated using two simulation scenarios: an induced resistance scenario and a nominal scenario to highlight the performance over a reference zone MPC with glucose ROC weighting only. The continuous adaption scheme resulted in consistent improvement for the entire glucose range without incurring additional risk of hypoglycemia. For the induced resistance and no feedforward bolus scenario, the percent time in 70-180 mg/dL was higher (53.5% versus 48.9%, p<0.001) with larger improvement in the overnight percent time in tighter glucose range 70-140 mg/dL (70.9% versus 52.9%, p<0.001). The results from extensive simulations, as well as clinical validation in three different outpatient studies demonstrate the utility and safety of the proposed zone MPC.