Anticipation of Historical Exercise Patterns by a Novel Artificial Pancreas System Reduces Hypoglycemia During and After Moderate-Intensity Physical Activity in People with Type 1 Diabetes

Abstract

Objective: Physical activity is a major challenge to glycemic control for people with type 1 diabetes. Moderate-intensity exercise often leads to steep decreases in blood glucose and hypoglycemia that closed-loop control systems have so far failed to protect against, despite improving glycemic control overall. Research Design and Methods: Fifteen adults with type 1 diabetes (42 ± 13.5 years old; hemoglobin A1c 6.6% ± 1.0%; 10F/5M) participated in a randomized crossover clinical trial comparing two hybrid closed-loop (HCL) systems, a state-of-the-art hybrid model predictive controller and a modified system designed to anticipate and detect unannounced exercise (APEX), during two 32-h supervised admissions with 45 min of planned moderate activity, following 4 weeks of data collection. Primary outcome was the number of hypoglycemic episodes during exercise. Continuous glucose monitor (CGM)-based metrics and hypoglycemia are also reported across the entire admissions. Results: The APEX system reduced hypoglycemic episodes overall (9 vs. 33; P = 0.02), during exercise (5 vs. 13; P = 0.04), and in the 4 h following (2 vs. 11; P = 0.02). Overall CGM median percent time <70 mg/dL decreased as well (0.3% vs. 1.6%; P = 0.004). This protection was obtained with no significant increase in time >180 mg/dL (18.5% vs. 16.6%, P = 0.15). Overnight control was notable for both systems with no hypoglycemia, median percent in time 70-180 mg/dL at 100% and median percent time 70-140 mg/dL at ∼96% for both. Conclusions: A new closed-loop system capable of anticipating and detecting exercise was proven to be safe and feasible and outperformed a state-of-the-art HCL, reducing participants' exposure to hypoglycemia during and after moderate-intensity physical activity. ClinicalTrials.gov NCT03859401.

Keywords: Artificial pancreas; Closed-loop system; Disturbance anticipation; Moderate-intensity exercise.

Conflict of interest statement

S.A.B. reports receiving grant support and supplies, paid to her institution from Tandem Diabetes Care, Insulet, and Tolerion, and supplies, provided to her institution, from Dexcom and Roche Diagnostics outside the submitted work. M.D.B. has received honoraria and travel reimbursement from Dexcom and Tandem, and research support from Dexcom, Novo Nordisk, and Tandem. No other potential conflicts of interest relevant to this article were reported.

Figures

FIG. 1.

Study protocol. (A) Participants were admitted twice to test one of the artificial pancreas systems in a randomized order. (B) Both admissions followed the same time line.

FIG. 2.

CGM and insulin in the hours before and after exercise are expected for APEX (red) and HCL (blue). (A, B) Correspond to exercise day (gray banner) and (C, D) to sedentary day. (A, C) CGM glucose values median (filled line), quartiles (envelopes), and minimum/maximum (dotted lines). Triangles are hypoglycemia treatments. (B, D) Insulin injections median (filled line) and quartiles (envelopes). APEX; CGM, continuous glucose monitor; HCL, hybrid closed-loop.

FIG. 3.

Insulin infusion during different periods of interest (box plots). (A) Pre-exercise period [15:30–17:00], exercise [17:00–19:00], evening [19:00–23:00], and overnight [23:00–7:00] for day 1. Presedentary [15:30–17:00], sedentary [17:00–19:00] for day 2. (B) Overall. (C) Dinner bolus.