Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes.


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
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

209-219

Subventions

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

Type : CommentIn
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Informations de copyright

Copyright © 2022 Massachusetts Medical Society.

Auteurs

Julia Ware (J)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Janet M Allen (JM)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Charlotte K Boughton (CK)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Malgorzata E Wilinska (ME)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Sara Hartnell (S)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Ajay Thankamony (A)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Carine de Beaufort (C)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Ulrike Schierloh (U)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Elke Fröhlich-Reiterer (E)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Julia K Mader (JK)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Thomas M Kapellen (TM)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Birgit Rami-Merhar (B)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Martin Tauschmann (M)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Katrin Nagl (K)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Sabine E Hofer (SE)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Fiona M Campbell (FM)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

James Yong (J)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Korey K Hood (KK)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Julia Lawton (J)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Stephane Roze (S)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Judy Sibayan (J)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Laura E Bocchino (LE)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Craig Kollman (C)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

Roman Hovorka (R)

From the Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science (J.W., J.M.A., C.K.B., M.E.W., R.H.) and the Department of Paediatrics (J.W., M.E.W., A.T., R.H.), University of Cambridge, and the Wolfson Diabetes and Endocrine Clinic, Cambridge University Hospitals NHS Foundation Trust (S.H.), Cambridge, the Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds (F.M.C., J.Y.), and Usher Institute, University of Edinburgh, Edinburgh (J.L.) - all in the United Kingdom; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg (C.B., U.S.); the Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, Brussels (C.B.); the Department of Pediatric and Adolescent Medicine (E.F.-R.), and the Division of Endocrinology and Diabetology, Department of Internal Medicine (J.K.M.), Medical University of Graz, Graz, the Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna (B.R.-M., M.T., K.N.), and the Department of Pediatrics I, Medical University of Innsbruck, Innsbruck (S.E.H.) - all in Austria; the Hospital for Children and Adolescents, University of Leipzig, Leipzig, and the Hospital for Children and Adolescents "am Nicolausholz," Bad Kösen - both in Germany (T.M.K.); the Division of Pediatric Endocrinology, Stanford University, Stanford, CA (K.K.H.); Vyoo Agency, Lyon, France (S.R.); and the Jaeb Center for Health Research, Tampa, FL (J.S., L.E.B., C.K.).

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