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Randomized Controlled Trial
. 2021 Dec 1;175(12):1227-1235.
doi: 10.1001/jamapediatrics.2021.3965.

Effect of a Hybrid Closed-Loop System on Glycemic and Psychosocial Outcomes in Children and Adolescents With Type 1 Diabetes: A Randomized Clinical Trial

Mary B Abraham  1   2   3 , Martin de Bock  1   2   3 , Grant J Smith  2 , Julie Dart  1   2 , Janice M Fairchild  4 , Bruce R King  5 , Geoffrey R Ambler  6 , Fergus J Cameron  7 , Sybil A McAuley  8   9 , Anthony C Keech  10 , Alicia Jenkins  8   9   10 , Elizabeth A Davis  1   2   3 , David N O'Neal  8   9 , Timothy W Jones  1   2   3 ; Australian Juvenile Diabetes Research Fund Closed-Loop Research group
Collaborators, Affiliations
Randomized Controlled Trial

Effect of a Hybrid Closed-Loop System on Glycemic and Psychosocial Outcomes in Children and Adolescents With Type 1 Diabetes: A Randomized Clinical Trial

Mary B Abraham et al. JAMA Pediatr. .

Abstract

Importance: Hybrid closed-loop (HCL) therapy has improved glycemic control in children and adolescents with type 1 diabetes; however, the efficacy of HCL on glycemic and psychosocial outcomes has not yet been established in a long-term randomized clinical trial.

Objective: To determine the percentage of time spent in the target glucose range using HCL vs current conventional therapies of continuous subcutaneous insulin infusion or multiple daily insulin injections with or without continuous glucose monitoring (CGM).

Design, setting, and participants: This 6-month, multicenter, randomized clinical trial included 172 children and adolescents with type 1 diabetes; patients were recruited between April 18, 2017, and October 4, 2019, in Australia. Data were analyzed from July 25, 2020, to February 26, 2021.

Interventions: Eligible participants were randomly assigned to either the control group for conventional therapy (continuous subcutaneous insulin infusion or multiple daily insulin injections with or without CGM) or the intervention group for HCL therapy.

Main outcomes and measures: The primary outcome was the percentage of time in range (TIR) within a glucose range of 70 to 180 mg/dL, measured by 3-week masked CGM collected at the end of the study in both groups. Secondary outcomes included CGM metrics for hypoglycemia, hyperglycemia, and glycemic variability and psychosocial measures collected by validated questionnaires.

Results: A total of 135 patients (mean [SD] age, 15.3 [3.1] years; 76 girls [56%]) were included, with 68 randomized to the control group and 67 to the HCL group. Patients had a mean (SD) diabetes duration of 7.7 (4.3) years and mean hemoglobin A1c of 64 (11) mmol/mol, with 110 participants (81%) receiving continuous subcutaneous insulin infusion and 72 (53%) receiving CGM. In the intention-to-treat analyses, TIR increased from a mean (SD) of 53.1% (13.0%) at baseline to 62.5% (12.0%) at the end of the study in the HCL group and from 54.6% (12.5%) to 56.1% (12.2%) in the control group, with a mean adjusted difference between the 2 groups of 6.7% (95% CI, 2.7%-10.8%; P = .002). Hybrid closed-loop therapy also reduced the time that patients spent in a hypoglycemic (<70 mg/dL) range (difference, -1.9%; 95% CI, -2.5% to -1.3%) and improved glycemic variability (coefficient of variation difference, -5.7%; 95% CI, -10.2% to -0.9%). Hybrid closed-loop therapy was associated with improved diabetes-specific quality of life (difference, 4.4 points; 95% CI, 0.4-8.4 points), with no change in diabetes distress. There were no episodes of severe hypoglycemia or diabetic ketoacidosis in either group.

Conclusions and relevance: In this randomized clinical trial, 6 months of HCL therapy significantly improved glycemic control and quality of life compared with conventional therapy in children and adolescents with type 1 diabetes.

Trial registration: ANZCTR identifier: ACTRN12616000753459.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Abraham reported receiving speaker honoraria fees from Medtronic outside the submitted work. Dr de Bock reported receiving grants from Medtronic outside the submitted work. Mr Smith reported receiving grants from the Juvenile Diabetes Research Fund and the National Health and Medical Research Council. Dr Ambler reported receiving grants from the Juvenile Diabetes Research Fund Australia. Dr McAuley reported receiving grants from the Juvenile Diabetes Research Fund during the conduct of the study; personal fees (honoraria) from Lilly and personal fees (advisory panel) from Medtronic; personal fees (honoraria) from Roche; and personal fees (honoraria) from Sanofi outside the submitted work. Dr Keech reported receiving grants from the Juvenile Diabetes Research Fund Australia (a proportion of which was paid to the University of Sydney) during the conduct of the study. Dr Jenkins reported receiving grants from the Juvenile Diabetes Research Fund Australia paid to the university during the conduct of the study. Dr Jones reported receiving grants from the Juvenile Diabetes Research Fund for study costs and grants from Perth Childrens Hospital Foundation for study costs during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
CSII indicates continuous subcutaneous insulin infusion; HCL, hybrid closed loop; MDI, multiple daily insulin. aData on insulin regimen were available in 31 patients (21 with CSII/10 MDI and 15 who were sensor naive). bOther indicates that 6 withdrawals were participant initiated and 1 was investigator initiated. cTwenty-eight sensor naive. dThirty-five sensor naive. eSeven CSII/3 MDI; 4 sensor naive. fThree CSII/1 MDI; 3 sensor naive.
Figure 2.
Figure 2.. Percentage of Time With Glucose Level in Target Range
A, Percentage time in range at baseline, midstudy, and at the end of the study from masked continuous glucose monitoring in the participants of the control and intervention group. Whiskers represent 95% CIs. B, Envelope plot of time in range by the hour of the day from the masked continuous glucose monitoring during the last 3 weeks of the trial in the participants of the control and intervention group. Solid lines denote median values, shaded regions represent the IQR, and dashed lines represent the boundaries for target glycemia. HCL indicates hybrid closed loop.
See this image and copyright information in PMC

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