The effect of closed-loop glucose control on C-peptide secretion in youth with newly diagnosed type 1 diabetes: the CLOuD RCT
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All Authors
Boughton,Charlotte K.
Allen,Janet M.
Ware,Julia
Wilinska,Malgorzata E.
Hartnell,Sara
Thankamony,Ajay
Randell,Tabitha
Ghatak,Atrayee
Besser,Rachel E. J.
Elleri,Daniela
LTHT Author
Campbell, Fiona M
LTHT Department
Leeds Children's Hospital
Children & Young People's Diabetes
Children & Young People's Diabetes
Non Medic
Publication Date
2024
Item Type
Article
Language
Subject
Subject Headings
Abstract
Background: We assessed whether a sustained period of intensive glucose control with hybrid closedloop for 12 months following diagnosis of type 1 diabetes in children and adolescents can preserve C-peptide secretion compared to standard insulin therapy. Methods: In an open-label, multicentre, randomised, parallel trial, youth aged 10-16.9 years were randomised within 21 days of type 1 diabetes diagnosis to hybrid closed-loop or standard insulin therapy (control). Primary end point was the difference in mixed-meal C-peptide area under the curve 12 months post diagnosis. Key secondary end points included time spent in target glucose range, glycated haemoglobin and time spent below target glucose range at 12 months. Analysis was by intention to treat. The Closed Loop from Onset in Type 1 Diabetes consortium secured external funding for participants to continue on beyond 12 months, but the funding by National Institute for Health and Care Research and the results reported here refer only to the 12 months follow-up. Results: We randomised 97 participants (mean � standard deviation age 12 � 2 years), 51 to closedloop and 46 to control therapy. There was no difference in C-peptide area under the curve at 12 months between groups geometric mean (interquartile range) closed-loop (n = 46): 0.35 pmol/ml (0.16, 0.49) vs. control (n = 37): 0.46 pmol/ml (0.22, 0.69); mean adjusted difference -0.06 (95% confidence interval -0.14 to 0.03); p = 0.19]. The proportion of time in target range 3.9-10.0 mmol/l based on 14-day masked LibrePro (Abbott Diabetes Care, Maidenhead, UK) sensor glucose data at 12 months was 10 percentage points (95% confidence interval 2 to 17) higher in the closed-loop group (64 � 14%) compared to control group (54 � 23%). Arithmetic mean glycated haemoglobin A1c was lower in the closed-loop group by 4 mmol/mol (0.4%) 95% confidence interval 0 to 8 mmol/mol (0.0% to 0.7%)] at 12 months. The mean difference in time spent < 3.9 mmol/l between groups was 0.9 percentage points (95% confidence interval -1.0 to 2.8). Three severe hypoglycaemic events occurred in the closed-loop group (two participants), and one in the control group; one diabetic ketoacidosis occurred in the closed-loop group. Conclusions: A sustained period of hybrid closed-loop glucose control following diagnosis of type 1 diabetes in children and adolescents does not slow down the decline in residual C-peptide secretion compared with standard insulin therapy. Despite the lack of effect on C-peptide, glycaemic control was sustained in the closed-loop group, whereas glycaemic control deteriorated in the control group 6 to 9 months after diagnosis and closed-loop safely accommodated the variability in exogenous insulin requirements which occur with beta-cell recovery post diagnosis. Limitations of the study included no central measurement of auto-antibodies at diagnosis. There was imbalance in the rate of diabetic ketoacidosis at diagnosis which is associated with a more rapid decline in C-peptide secretion, but this was adjusted for in the analyses. This highlights the need for improved therapies to allow youth to achieve recommended glycaemic targets from onset of type 1 diabetes irrespective of the lack of effect on residual C-peptide secretion. Future work includes ongoing follow-up of the study population for up to 4 years after diagnosis to observe how any differences in glycaemic control between treatment groups develop over time.
Journal
Efficacy & Mechanism Evaluation (EME)