title: 2 month evening and night closed-loop glucose control in patients with type 1 diabetes under free-living conditions: a randomised crossover trial.
abstract: BACKGROUND
  An artificial pancreas (AP) that can be worn at home from dinner to waking up in the morning might be safe and efficient for first routine use in patients with type 1 diabetes. We assessed the effect on glucose control with use of an AP during the evening and night plus patient-managed sensor-augmented pump therapy (SAP) during the day, versus 24 h use of patient-managed SAP only, in free-living conditions.
  
  
  METHODS
  In a crossover study done in medical centres in France, Italy, and the Netherlands, patients aged 18-69 years with type 1 diabetes who used insulin pumps for continuous subcutaneous insulin infusion were randomly assigned to 2 months of AP use from dinner to waking up plus SAP use during the day versus 2 months of SAP use only under free-living conditions. Randomisation was achieved with a computer-generated allocation sequence with random block sizes of two, four, or six, masked to the investigator. Patients and investigators were not masked to the type of intervention. The AP consisted of a continuous glucose monitor (CGM) and insulin pump connected to a modified smartphone with a model predictive control algorithm. The primary endpoint was the percentage of time spent in the target glucose concentration range (3·9-10·0 mmol/L) from 2000 to 0800 h. CGM data for weeks 3-8 of the interventions were analysed on a modified intention-to-treat basis including patients who completed at least 6 weeks of each intervention period. The 2 month study period also allowed us to asses HbA1c as one of the secondary outcomes. This trial is registered with ClinicalTrials.gov, number NCT02153190.
  
  
  RESULTS
  During 2000-0800 h, the mean time spent in the target range was higher with AP than with SAP use: 66·7% versus 58·1% (paired difference 8·6% [95% CI 5·8 to 11·4], p<0·0001), through a reduction in both mean time spent in hyperglycaemia (glucose concentration >10·0 mmol/L; 31·6% vs 38·5%; -6·9% [-9·8% to -3·9], p<0·0001) and in hypoglycaemia (glucose concentration <3·9 mmol/L; 1·7% vs 3·0%; -1·6% [-2·3 to -1·0], p<0·0001). Decrease in mean HbA1c during the AP period was significantly greater than during the control period (-0·3% vs -0·2%; paired difference -0·2 [95% CI -0·4 to -0·0], p=0·047), taking a period effect into account (p=0·0034). No serious adverse events occurred during this study, and none of the mild-to-moderate adverse events was related to the study intervention.
  
  
  CONCLUSIONS
  Our results support the use of AP at home as a safe and beneficial option for patients with type 1 diabetes. The HbA1c results are encouraging but preliminary.
  
  
  BACKGROUND
  European Commission.
authors.affiliation: Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. Electronic address: j.kropff@amc.nl.
authors.forename: Jort
authors.initials: J
authors.lastname: Kropff
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Del Favero
authors.affiliation: Department of Endocrinology, Diabetes, Nutrition Montpellier University Hospital, INSERM Clinical Investigation Centre 1411, and Institute of Functional Genomics, CNRS UMR 5203, INSERM U1191, University of Montpellier, Montpellier, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Place
authors.affiliation: Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Toffanin
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Visentin
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Monaro
authors.affiliation: Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Messori
authors.affiliation: Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Di Palma
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
authors.forename: Giordano
authors.initials: G
authors.lastname: Lanzola
authors.affiliation: Department of Endocrinology, Diabetes, Nutrition Montpellier University Hospital, INSERM Clinical Investigation Centre 1411, and Institute of Functional Genomics, CNRS UMR 5203, INSERM U1191, University of Montpellier, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Farret
authors.affiliation: Unit of Metabolic Diseases, Department of Internal Medicine-DIM, University of Padova, Padova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Boscari
authors.affiliation: Unit of Metabolic Diseases, Department of Internal Medicine-DIM, University of Padova, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galasso
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy; Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
authors.affiliation: Unit of Metabolic Diseases, Department of Internal Medicine-DIM, University of Padova, Padova, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: Center for Diabetes Technology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Keith-Hynes
authors.affiliation: Center for Diabetes Technology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Kovatchev
authors.affiliation: Unit of Metabolic Diseases, Department of Internal Medicine-DIM, University of Padova, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Bruttomesso
authors.affiliation: Department of Information Engineering, University of Padova, Padova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.affiliation: Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: J Hans
authors.initials: JH
authors.lastname: DeVries
authors.affiliation: Department of Endocrinology, Diabetes, Nutrition Montpellier University Hospital, INSERM Clinical Investigation Centre 1411, and Institute of Functional Genomics, CNRS UMR 5203, INSERM U1191, University of Montpellier, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Renard
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy; Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.
authors.forename: Lalo
authors.initials: L
authors.lastname: Magni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; 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; D008991:Monitoring, Physiologic; D019397:Pancreas, Artificial; D000068997:Smartphone; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin