Using an Online Disturbance Rejection and Anticipation System to Reduce Hyperglycemia in a Fully Closed-Loop Artificial Pancreas System

Abstract

Hyperglycemia following meals is a recurring challenge for people with type 1 diabetes, and even the most advanced available automated systems currently require manual input of carbohydrate amounts. To progress toward fully automated systems, we present a novel control system that can automatically deliver priming boluses and/or anticipate eating behaviors to improve postprandial full closed-loop control. A model predictive control (MPC) system was enhanced by an automated bolus system reacting to early glucose rise and/or a multistage MPC (MS-MPC) framework to anticipate historical patterns. Priming was achieved by detecting large glycemic disturbances, such as meals, and delivering a fraction of the patient’s total daily insulin (TDI) modulated by the disturbance’s likelihood (bolus priming system [BPS]). In the anticipatory module, glycemic disturbance profiles were generated from historical data using clustering to group days with similar behaviors; the probability of each cluster is then evaluated at every controller step and informs the MS-MPC framework to anticipate each profile. We tested four configurations: MPC, MPC + BPS, MS-MPC, and MS-MPC + BPS in simulation to contrast the effect of each controller module. Postprandial time in range was highest for MS-MPC + BPS: 60.73 ± 25.39%, but improved with each module: MPC + BPS: 56.95±25.83 and MS-MPC: 54.83 ± 26.00%, compared with MPC: 51.79 ± 26.12%. Exposure to hypoglycemia was maintained for all controllers (time below 70 mg/dL <0.5%), and improvement came primarily from a reduction in postprandial time above range (MS-MPC + BPS: 39.10 ± 25.32%, MPC + BPS: 42.99 ± 25.81%, MS-MPC: 45.09 ± 25.96%, MPC: 48.18 ± 26.09%). The BPS and anticipatory disturbance profiles improved blood glucose control and were most efficient when combined.