title: Feasibility of Long-Term Closed-Loop Control: A Multicenter 6-Month Trial of 24/7 Automated Insulin Delivery.
abstract: In the past few years, the artificial pancreas-the commonly accepted term for closed-loop control (CLC) of blood glucose in diabetes-has become a hot topic in research and technology development. In the summer of 2014, we initiated a 6-month trial evaluating the safety of 24/7 CLC during free-living conditions.
  
  
  
  Following an initial 1-month Phase 1, 14 individuals (10 males/4 females) with type 1 diabetes at three clinical centers in the United States and one in Italy continued with a 5-month Phase 2, which included 24/7 CLC using the wireless portable Diabetes Assistant (DiAs) developed at the University of Virginia Center for Diabetes Technology. Median subject characteristics were age 45 years, duration of diabetes 27 years, total daily insulin 0.53 U/kg/day, and baseline HbA1c 7.2% (55 mmol/mol).
  
  
  
  Compared with the baseline observation period, the frequency of hypoglycemia below 3.9 mmol/L during the last 3 months of CLC was lower: 4.1% versus 1.3%, P < 0.001. This was accompanied by a downward trend in HbA1c from 7.2% (55 mmol/mol) to 7.0% (53 mmol/mol) at 6 months. HbA1c improvement was correlated with system use (Spearman r = 0.55). The user experience was favorable with identified benefit particularly at night and overall trust in the system. There were no serious adverse events, severe hypoglycemia, or diabetic ketoacidosis.
  
  
  
  We conclude that CLC technology has matured and is safe for prolonged use in patients' natural environment. Based on these promising results, a large randomized trial is warranted to assess long-term CLC efficacy and safety.
authors.affiliation: 1 University of Virginia Center for Diabetes Technology, Charlottesville, Virginia.
authors.forename: Boris
authors.initials: B
authors.lastname: Kovatchev
authors.affiliation: 2 Jaeb Center for Health Research , Tampa, Florida.
authors.forename: Peiyao
authors.initials: P
authors.lastname: Cheng
authors.affiliation: 1 University of Virginia Center for Diabetes Technology, Charlottesville, Virginia.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Anderson
authors.affiliation: 3 William Sansum Diabetes Center , Santa Barbara, California.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Pinsker
authors.affiliation: 4 University of Padova , Padova, Italy .
authors.forename: Federico
authors.initials: F
authors.lastname: Boscari
authors.affiliation: 5 Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Stanford University School of Medicine , Stanford, California.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Buckingham
authors.affiliation: 6 Department of Chemical Engineering, University of California , Santa Barbara, Santa Barbara, California.|7 Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University , Cambridge, Massachusetts.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
authors.affiliation: 5 Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Stanford University School of Medicine , Stanford, California.
authors.forename: Korey K
authors.initials: KK
authors.lastname: Hood
authors.affiliation: 1 University of Virginia Center for Diabetes Technology, Charlottesville, Virginia.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: 1 University of Virginia Center for Diabetes Technology, Charlottesville, Virginia.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Breton
authors.affiliation: 1 University of Virginia Center for Diabetes Technology, Charlottesville, Virginia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chernavvsky
authors.affiliation: 3 William Sansum Diabetes Center , Santa Barbara, California.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Bevier
authors.affiliation: 3 William Sansum Diabetes Center , Santa Barbara, California.
authors.forename: Paige K
authors.initials: PK
authors.lastname: Bradley
authors.affiliation: 4 University of Padova , Padova, Italy .
authors.forename: Daniela
authors.initials: D
authors.lastname: Bruttomesso
authors.affiliation: 4 University of Padova , Padova, Italy .
authors.forename: Simone
authors.initials: S
authors.lastname: Del Favero
authors.affiliation: 4 University of Padova , Padova, Italy .
authors.forename: Roberta
authors.initials: R
authors.lastname: Calore
authors.affiliation: 4 University of Padova , Padova, Italy .
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.affiliation: 4 University of Padova , Padova, Italy .
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.affiliation: 5 Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Stanford University School of Medicine , Stanford, California.
authors.forename: Trang T
authors.initials: TT
authors.lastname: Ly
authors.affiliation: 5 Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Stanford University School of Medicine , Stanford, California.
authors.forename: Satya
authors.initials: S
authors.lastname: Shanmugham
authors.affiliation: 6 Department of Chemical Engineering, University of California , Santa Barbara, Santa Barbara, California.|7 Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University , Cambridge, Massachusetts.
authors.forename: Eyal
authors.initials: E
authors.lastname: Dassau
authors.affiliation: 2 Jaeb Center for Health Research , Tampa, Florida.
authors.forename: Craig
authors.initials: C
authors.lastname: Kollman
authors.affiliation: 2 Jaeb Center for Health Research , Tampa, Florida.
authors.forename: John W
authors.initials: JW
authors.lastname: Lum
authors.affiliation: 2 Jaeb Center for Health Research , Tampa, Florida.
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D019397:Pancreas, Artificial
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Artificial pancreas.; Automated insulin delivery (AID); Closed-loop control; Continuous glucose monitoring (CGM); Insulin pump therapy