부산대학교 도서관

Summary Background Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods In a multicentre, multinational, parallel randomised controlled trial, participants aged 6--18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA.sub.1c levels between 53 and 86 mmol/mol (7*0--10*0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA.sub.1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA.sub.1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings Of 147 people initially screened, 133 participants (mean age 13*0 years [SD 2*8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA.sub.1c was 8*2% (SD 0*7) in the closed-loop group and 8*3% (0*7) in the control group. At 6 months, HbA.sub.1c was lower in the closed-loop group than in the control group (between-group difference -3*5 mmol/mol (95% CI -6*5 to -0*5 [--0*32 percentage points, -0*59 to -0*04]; p=0*023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26--53]), but consistently high with CamAPS FX (93% [88--96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding National Institute of Diabetes and Digestive and Kidney Diseases. Author Affiliation: (a) Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK (b) Department of Paediatrics, University of Cambridge, Cambridge, UK (c) Department of Diabetes & Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (d) Department of Paediatric Diabetes and Endocrinology, Nottingham University Hospitals NHS Trust, Nottingham, UK (e) Department of Paediatric Diabetes, Leeds Children's Hospital, Leeds, UK (f) Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA (g) Division of Pediatric Endocrinology, Stanford University, Stanford, CA, USA (h) Department of Paediatric Endocrinology and Diabetes, Southampton Children's Hospital, Southampton General Hospital, Southampton, UK (i) Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA (j) Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Health System, Jacksonville, FL, USA (k) Oxford University Hospitals NHS Foundation Trust, NIHR Oxford Biomedical Research Centre, Oxford, UK (l) Department of Paediatrics, University of Oxford, Oxford, UK (m) Alder Hey Children's Hospital, Liverpool, UK (n) Department of Pediatrics, Yale University, New Haven, CT, USA (o) Department of Pharmaceutical and Health Economics, School of Pharmacy, University of Southern California, Los Angeles, CA, USA (p) The Jaeb Center for Health Research, Tampa, FL, USA * Correspondence: Prof Roman Hovorka, University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK (footnote)[Dagger] JW and CKB contributed equally Byline: Julia Ware, MD (a,b,[Dagger]), Charlotte K Boughton, PhD (a,c,[Dagger]), Janet M Allen, RN (a), Malgorzata E Wilinska, PhD (a,b), Martin Tauschmann, PhD (a,b), Louise Denvir, MD (d), Ajay Thankamony, MPhil (b), Fiona M Campbell, MD (e), Prof R Paul Wadwa, MD (f), Prof Bruce A Buckingham, MD (g), Nikki Davis, MD (h), Prof Linda A DiMeglio, MD (i), Nelly Mauras, MD (j), Rachel E J Besser, PhD (k,l), Atrayee Ghatak, MD (m), Prof Stuart A Weinzimer, MD (n), Prof Korey K Hood, PhD (g), D Steven Fox, MD (o), Lauren Kanapka, MSc (p), Craig Kollman, PhD (p), Judy Sibayan, MPH (p), Roy W Beck, PhD (p), Prof Roman Hovorka, PhD [rh347@cam.ac.uk] (a,b), R Hovorka, C L Acerini, A Thankamony, J M Allen, C K Boughton, K Dovc, D B Dunger, J Ware, G Musolino, M Tauschmann, M E Wilinska, J F Hayes, S Hartnell, S Slegtenhorst, Y Ruan, M Haydock, J Mangat, L Denvir, SK Kanthagnany, J Law, T Randell, P Sachdev, M Saxton, A Coupe, S Stafford, A Ball, R Keeton, R Cresswell, L Crate, H Cripps, H Fazackerley, L Looby, H Navarra, C Saddington, V Smith, V Verhoeven, S Bratt, N Khan, L Moyes, K Sandhu, C West, R P Wadwa, G Alonso, G Forlenza, R Slover, L Towers, C Berget, A Coakley, E Escobar, E Jost, S Lange, L Messer, K Thivener, F M Campbell, J Yong, E Metcalfe, M Allen, S Ambler, S Waheed, J Exall, J Tulip, B A Buckingham, L Ekhlaspour, D Maahs, L Norlander, T Jacobson, M Twon, C Weir, B Leverenz, J Keller, N Davis, A Kumaran, N Trevelyan, H Dewar, G Price, G Crouch, R Ensom, L Haskell, LM Lueddeke, N Mauras, M Benson, K Bird, K Englert, J Permuy, K Ponthieux, J Marrero-Hernandez, L A DiMeglio, H Ismail, H Jolivette, J Sanchez, S Woerner, M Kirchner, M Mullen, M Tebbe, R EJ Besser, S Basu, R London, T Makaya, F Ryan, C Megson, J Bowen-Morris, J Haest, R Law, I Stamford, A Ghatak, M Deakin, K Phelan, K Thornborough, J Shakeshaft, S A Weinzimer, E Cengiz, J L Sherr, M Van Name, K Weyman, L Carria, A Steffen, M Zgorski, J Sibayan, R W Beck, S Borgman, J Davis, J Rusnak, A Hellman, P Cheng, L Kanapka, C Kollman, C McCarthy, S Chalasani, K K Hood, S Hanes, J Viana, M Lanning, D S Fox, G Arreaza-Rubin, T Eggerman, N Green, R Janicek, D Gabrielson, S H Belle, J Castle, J Green, L Legault, S M Willi, C Wysham