title: Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial.
abstract: BACKGROUND
  Additional benefits of the dual-hormone (insulin and glucagon) artificial pancreas compared with the single-hormone (insulin alone) artificial pancreas have not been assessed in young people in outpatient unrestricted conditions. We evaluated the efficacy of three systems for nocturnal glucose control in children and adolescents with type 1 diabetes.
  
  
  METHODS
  We did a randomised, three-way, crossover trial in children aged 9-17 years with type 1 diabetes attending a diabetes camp in Canada. With use of sealed envelopes, children were randomly assigned in a 1:1:1:1:1:1 ratio with blocks of six to different sequences of the three interventions (single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional continuous subcutaneous insulin pump therapy). Each intervention was applied for 3 consecutive nights. Participants, study staff, and endpoint assessors were not masked. The primary outcome was the percentage of time spent with glucose concentrations lower than 4·0 mmol/L from 2300 h to 0700 h. Analysis was by intention to treat. A p value of less than 0·0167 was regarded as significant. This study is registered with ClinicalTrials.gov, number NCT02189694.
  
  
  RESULTS
  Between June 30, 2014, and Aug 9, 2014, we enrolled 33 children of mean age 13·3 years (SD 2·3; range 9-17). The time spent at a glucose concentration lower than 4·0 mmol/L was median 0% (IQR 0·0-2·4) during nights with the dual-hormone artificial pancreas, 3·1% (0·0-6·9) during nights with the single-hormone artificial pancreas (p=0·032), and 3·4% (0-11·0) during nights with conventional pump therapy (p=0·0048 compared with dual-hormone artificial pancreas and p=0·32 compared with single-hormone artificial pancreas). 15 hypoglycaemic events (<3·1 mmol/L for 20 min measured by sensor then confirmed with capillary glucose <4·0 mmol/L) were noted during nights with conventional pump therapy compared with four events with the single-hormone system and no events with the dual-hormone system. None of the assessed outcomes varied with the order in which children and young adults were assigned interventions.
  
  
  CONCLUSIONS
  The dual-hormone artificial pancreas could improve nocturnal glucose control in children and adolescents with type 1 diabetes. Longer and larger outpatient studies are now needed.
  
  
  BACKGROUND
  Canadian Diabetes Association, Fondation J A De Sève.
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada. Electronic address: ahmad.haidar@mail.mcgill.ca.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Haidar
authors.affiliation: Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Legault
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Matteau-Pelletier
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors.forename: Virginie
authors.initials: V
authors.lastname: Messier
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada.
authors.forename: Maryse
authors.initials: M
authors.lastname: Dallaire
authors.affiliation: The Research Center of the Université de Montréal Hospital Center, Montreal, QC, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Ladouceur
authors.affiliation: Institut de recherches cliniques de Montréal, Montreal, QC, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada; Nutrition Department, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada; Montreal Diabetes Research Center, Montreal, QC, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
mesh_terms: D000293:Adolescent; D001786:Blood Glucose; D002170:Canada; D002648:Child; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015918:Infusion Pumps, Implantable; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D008297:Male; D010045:Outpatients; D019397:Pancreas, Artificial; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon