A new real-time algorithm for preventive hypotreatments generation allows reducing frequency and duration of hypoglycemia

Objective: American Diabetes Association (ADA) guidelines suggest that subjects with type 1 diabetes (T1D) consume hypotreatments (HTs) whenever hypoglycemia is revealed/detected. However, such a strategy does not avoid the hypoglycemic event. In this work, we propose a new real-time algorithm, using continuous glucose monitoring (CGM) data, with the objective of triggering preventive HTs to reduce both frequency and duration of hypoglycemic events. Method: The new algorithm was designed to determine the severity of future hypoglycemia and to trigger preventive HTs by combining CGM values and trend as a measure of risk. The selected comparators were ADA guidelines and a prediction-based algorithm, in which the first HT is triggered based on a 30 min subject-specific prediction. Methods were assessed in-silico using a 7-day realistic simulation involving 100 virtual adults, generated by the UVA/Padova T1D simulator, using as performance metrics time in range (TIR), time in hypoglycemia (THypo), time in hyperglycemia (THyper), and the daily number of HTs (#HTs). Result: On median [25th–75th percentiles], ADA guidelines returns 15.1 [13.7–17.4] h/day in target, 22 [8–39] min/day in hypoglycemia and 509 [370–603] min/day in hyperglycemia, with 1.77 [0.69–2.70] HTs/day. Prediction increases TIR (15.5 [14.1–18.0] h/day), reduces THypo (13 [4–27] min/day) and THyper (495 [360–580] min/day), with 1.63 [0.89–2.39] HTs/day. The new algorithm outperforms both previous strategies, providing 15.7 [14.2–18.1] h/day in target, 10 [3–18] min/day in hypoglycemia, and 493 [349–576] min/day in hyperglycemia, also reducing the number of HTs to 1.5 [0.79–2.0]/day. Conclusion: The proposed algorithm efficiently generates preventive HTs, increasing TIR, decreasing both THypo and THyper, and, notably, lowering the number of required interventions per day, compared to both ADA guidelines and prediction-based algorithms.