Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes.
Algorithms
Blood Glucose
/ analysis
Child
Child, Preschool
Cross-Over Studies
Diabetes Mellitus, Type 1
/ drug therapy
Equipment Design
Female
Glycated Hemoglobin
/ analysis
Glycemic Control
/ instrumentation
Humans
Hyperglycemia
/ diagnosis
Hypoglycemic Agents
/ administration & dosage
Infant
Insulin
/ administration & dosage
Insulin Infusion Systems
Male
Pancreas, Artificial
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
20 01 2022
20 01 2022
Historique:
entrez:
19
1
2022
pubmed:
20
1
2022
medline:
27
1
2022
Statut:
ppublish
Résumé
The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear. In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed. A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval [CI], 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was -8.5 percentage points (95% CI, -9.9 to -7.1), the difference in the glycated hemoglobin level was -0.4 percentage points (95% CI, -0.5 to -0.3), and the difference in the mean sensor glucose level was -12.3 mg per deciliter (95% CI, -14.8 to -9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P = 0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred. A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT03784027.).
Sections du résumé
BACKGROUND
The possible advantage of hybrid closed-loop therapy (i.e., artificial pancreas) over sensor-augmented pump therapy in very young children with type 1 diabetes is unclear.
METHODS
In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy at seven centers across Austria, Germany, Luxembourg, and the United Kingdom. Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy (control). The primary end point was the between-treatment difference in the percentage of time that the sensor glucose measurement was in the target range (70 to 180 mg per deciliter) during each 16-week period. The analysis was conducted according to the intention-to-treat principle. Key secondary end points included the percentage of time spent in a hyperglycemic state (glucose level, >180 mg per deciliter), the glycated hemoglobin level, the mean sensor glucose level, and the percentage of time spent in a hypoglycemic state (glucose level, <70 mg per deciliter). Safety was assessed.
RESULTS
A total of 74 participants underwent randomization. The mean (±SD) age of the participants was 5.6±1.6 years, and the baseline glycated hemoglobin level was 7.3±0.7%. The percentage of time with the glucose level in the target range was 8.7 percentage points (95% confidence interval [CI], 7.4 to 9.9) higher during the closed-loop period than during the control period (P<0.001). The mean adjusted difference (closed-loop minus control) in the percentage of time spent in a hyperglycemic state was -8.5 percentage points (95% CI, -9.9 to -7.1), the difference in the glycated hemoglobin level was -0.4 percentage points (95% CI, -0.5 to -0.3), and the difference in the mean sensor glucose level was -12.3 mg per deciliter (95% CI, -14.8 to -9.8) (P<0.001 for all comparisons). The time spent in a hypoglycemic state was similar with the two treatments (P = 0.74). The median time spent in the closed-loop mode was 95% (interquartile range, 92 to 97) over the 16-week closed-loop period. One serious adverse event of severe hypoglycemia occurred during the closed-loop period. One serious adverse event that was deemed to be unrelated to treatment occurred.
CONCLUSIONS
A hybrid closed-loop system significantly improved glycemic control in very young children with type 1 diabetes, without increasing the time spent in hypoglycemia. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT03784027.).
Identifiants
pubmed: 35045227
doi: 10.1056/NEJMoa2111673
doi:
Substances chimiques
Blood Glucose
0
Glycated Hemoglobin A
0
Hypoglycemic Agents
0
Insulin
0
Banques de données
ClinicalTrials.gov
['NCT03784027']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
209-219Subventions
Organisme : Horizon 2020 Framework Programme
ID : 731560
Organisme : Juvenile Diabetes Research Foundation United States of America
ID : 22-2013-266 and 2-RSC-2019-828-M-N
Investigateurs
Roman Hovorka
(R)
Carlo L Acerini
(CL)
Ajay Thankamony
(A)
Charlotte K Boughton
(CK)
Klemen Dovc
(K)
Julia Ware
(J)
Gianluca Musolino
(G)
Malgorzata E Wilinska
(ME)
Janet M Allen
(JM)
Sara Hartnell
(S)
Yue Ruan
(Y)
Nicole Ashcroft
(N)
Matthew Haydock
(M)
Catherine Hill
(C)
Carine de Beaufort
(C)
Ulrike Schierloh
(U)
Muriel Fichelle
(M)
Dominique Schaeffer
(D)
Elke Fröhlich-Reiterer
(E)
Maria Fritsch
(M)
Hildegard Jasser-Nitsche
(H)
Julia K Mader
(JK)
Kerstin Faninger
(K)
Thomas M Kapellen
(TM)
Heike Bartelt
(H)
Alena Thiele
(A)
Birgit Rami-Merhar
(B)
Gabriele Berger
(G)
Nicole Blauensteiner
(N)
Renata Gellai
(R)
Katrin Nagl
(K)
Martin Tauschmann
(M)
Sarah Cvach
(S)
Sonja Katzenbeisser-Pawlik
(S)
Sabine E Hofer
(SE)
Daniela Abt
(D)
Anita Malik
(A)
Barbara Lanthaler
(B)
Matthias Wenzel
(M)
Fiona Campbell
(F)
James Yong
(J)
Emily Metcalfe
(E)
Majorie Allen
(M)
Sarah Ambler
(S)
Saima Waheed
(S)
Jane Exall
(J)
Joseph Tulip
(J)
Judy Sibayan
(J)
Roy Beck
(R)
Sarah Borgman
(S)
Julie Davis
(J)
Jessica Rusnak
(J)
Amanda Hellmann
(A)
Peiyao Cheng
(P)
Lauren Kanapka
(L)
Craig Kollman
(C)
Chris McCarthy
(C)
Sravanthi Chalasani
(S)
Julia Lawton
(J)
Barbara Kimbell
(B)
David Rankin
(D)
Ruth Hart
(R)
Korey K Hood
(KK)
Stéphane Roze
(S)
John Isitt
(J)
Alice Gregory
(A)
Juan Jose Madrid Valero
(JJ)
Timothy Jones
(T)
Chris Patterson
(C)
Peter Adolfsson
(P)
Commentaires et corrections
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Informations de copyright
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