Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness

Background: Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. Methods: Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. Results: Nine participants (median interquartile range (IQR) age 51 41, 59 years; 44% male; enrolment HYPO score 1183 1058, 1308; Clarke score 6 6, 6; n = 5 HCL; n = 4 control) completed the study. Time-in-range was higher using HCL vs control (70% 68, 74% vs 48% 44, 50%, P = .014). Time <70 mg/dL did not differ (HCL 3.8% 2.7, 3.9 vs control 6.5% 4.3, 8.6, P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 30.0, 39.2 vs 70.8 58.5, 72.4, P = .014). Following 6 months of HCL use, greater dopamine (24.0 12.3, 27.6 vs −18.5 −36.5, −4.8, P = .014), and growth hormone (6.3 4.6, 16.8 vs 0.5 −0.8, 3.0, P = .050) responses to hypoglycemia were observed. Conclusions: Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. Clinical trial registration: ACTRN12617000520336