title: Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study.
abstract: BACKGROUND
  Closed-loop insulin delivery is a promising option to improve glycaemic control and reduce the risk of hypoglycaemia. We aimed to assess whether overnight home use of automated closed-loop insulin delivery would improve glucose control.
  
  
  METHODS
  We did this open-label, multicentre, randomised controlled, crossover study between Dec 1, 2012, and Dec 23, 2014, recruiting patients from three centres in the UK. Patients aged 18 years or older with type 1 diabetes were randomly assigned to receive 4 weeks of overnight closed-loop insulin delivery (using a model-predictive control algorithm to direct insulin delivery), then 4 weeks of insulin pump therapy (in which participants used real-time display of continuous glucose monitoring independent of their pumps as control), or vice versa. Allocation to initial treatment group was by computer-generated permuted block randomisation. Each treatment period was separated by a 3-4 week washout period. The primary outcome was time spent in the target glucose range of 3·9-8·0 mmol/L between 0000 h and 0700 h. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01440140.
  
  
  RESULTS
  We randomly assigned 25 participants to initial treatment in either the closed-loop group or the control group, patients were later crossed over into the other group; one patient from the closed-loop group withdrew consent after randomisation, and data for 24 patients were analysed. Closed loop was used over a median of 8·3 h (IQR 6·0-9·6) on 555 (86%) of 644 nights. The proportion of time when overnight glucose was in target range was significantly higher during the closed-loop period compared to during the control period (mean difference between groups 13·5%, 95% CI 7·3-19·7; p=0·0002). We noted no severe hypoglycaemic episodes during the control period compared with two episodes during the closed-loop period; these episodes were not related to closed-loop algorithm instructions.
  
  
  CONCLUSIONS
  Unsupervised overnight closed-loop insulin delivery at home is feasible and could improve glucose control in adults with type 1 diabetes.
  
  
  BACKGROUND
  Diabetes UK.
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Hood
authors.initials: H
authors.lastname: Thabit
authors.affiliation: Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lubina-Solomon
authors.affiliation: Diabetes Research Group, King's College London, London, UK.
authors.forename: Marietta
authors.initials: M
authors.lastname: Stadler
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Lalantha
authors.initials: L
authors.lastname: Leelarathna
authors.affiliation: Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Walkinshaw
authors.affiliation: Diabetes Research Group, King's College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pernet
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Allen
authors.affiliation: Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Iqbal
authors.affiliation: Diabetes Research Group, King's College London, London, UK.
authors.forename: Pratik
authors.initials: P
authors.lastname: Choudhary
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Kavita
authors.initials: K
authors.lastname: Kumareswaran
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Marianna
authors.initials: M
authors.lastname: Nodale
authors.affiliation: Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Chloe
authors.initials: C
authors.lastname: Nisbet
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.affiliation: Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Katharine D
authors.initials: KD
authors.lastname: Barnard
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.affiliation: Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Heller
authors.affiliation: Diabetes Research Group, King's College London, London, UK.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Amiel
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.affiliation: Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK. Electronic address: rh347@cam.ac.uk.
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D019397:Pancreas, Artificial; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human