Integration of a Safety Module to Prevent Rebound Hypoglycemia in Closed-Loop Artificial Pancreas Systems

Background: With automated insulin delivery (AID) systems becoming widely adopted in the management of type 1 diabetes, we have seen an increase in occurrences of rebound hypoglycemia or generated hypoglycemia induced by the controller's response to rapid glucose rises following rescue carbohydrates. Furthermore, as AID systems aim to enable complete automation of prandial control, algorithms are designed to react even more strongly to glycemic rises. This work introduces a rebound hypoglycemia prevention layer (HypoSafe) that can be easily integrated into any AID system.

Methods: HypoSafe constrains the maximum permissible insulin delivery dose based on the minimum glucose reading from the previous hour and the current glucose level. To demonstrate its efficacy, we integrated HypoSafe into the latest University of Virginia (UVA) AID system and simulated two scenarios using the 100-adult cohort of the UVA/Padova T1D simulator: a nominal case including three unannounced meals, and another case where hypoglycemia was purposely induced by an overestimated manual bolus.

Results: In both simulation scenarios, rebound hypoglycemia events were reduced with HypoSafe (nominal: from 39 to 0, hypo-induced: from 55 to 7) by attenuating the commanded basal (nominal: 0.27U vs. 0.04U, hypo-induced: 0.27U vs. 0.03U) and bolus (nominal: 1.02U vs. 0.05U, hypo-induced: 0.43U vs. 0.02U) within the 30-minute interval after treating a hypoglycemia event. No clinically significant changes resulted for time in the range of 70 to 180 mg/dL or above 180 mg/dL.

Conclusion: HypoSafe was shown to be effective in reducing rebound hypoglycemia events without affecting achieved time in range when combined with an advanced AID system.