title: Multicenter closed-loop insulin delivery study points to challenges for keeping blood glucose in a safe range by a control algorithm in adults and adolescents with type 1 diabetes from various sites.
abstract: BACKGROUND
  The Control to Range Study was a multinational artificial pancreas study designed to assess the time spent in the hypo- and hyperglycemic ranges in adults and adolescents with type 1 diabetes while under closed-loop control. The controller attempted to keep the glucose ranges between 70 and 180 mg/dL. A set of prespecified metrics was used to measure safety.
  
  
  METHODS
  We studied 53 individuals for approximately 22 h each during clinical research center admissions. Plasma glucose level was measured every 15-30 min (YSI clinical laboratory analyzer instrument [YSI, Inc., Yellow Springs, OH]). During the admission, subjects received three mixed meals (1 g of carbohydrate/kg of body weight; 100 g maximum) with meal announcement and automated insulin dosing by the controller.
  
  
  RESULTS
  For adults, the mean of subjects' mean glucose levels was 159 mg/dL, and mean percentage of values 71-180 mg/dL was 66% overall (59% daytime and 82% overnight). For adolescents, the mean of subjects' mean glucose levels was 166 mg/dL, and mean percentage of values in range was 62% overall (53% daytime and 82% overnight). Whereas prespecified criteria for safety were satisfied by both groups, they were met at the individual level in adults only for combined daytime/nighttime and for isolated nighttime. Two adults and six adolescents failed to meet the daytime criterion, largely because of postmeal hyperglycemia, and another adolescent failed to meet the nighttime criterion.
  
  
  CONCLUSIONS
  The control-to-range system performed as expected: faring better overnight than during the day and performing with variability between patients even after individualization based on patients' prior settings. The system had difficulty preventing postmeal excursions above target range.
authors.affiliation: 1 Sansum Diabetes Research Institute , Santa Barbara, California.
authors.forename: Howard
authors.initials: H
authors.lastname: Zisser
authors.forename: Eric
authors.initials: E
authors.lastname: Renard
authors.forename: Boris
authors.initials: B
authors.lastname: Kovatchev
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Revital
authors.initials: R
authors.lastname: Nimri
authors.forename: Lalo
authors.initials: L
authors.lastname: Magni
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Buckingham
authors.forename: H Peter
authors.initials: HP
authors.lastname: Chase
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
authors.forename: John
authors.initials: J
authors.lastname: Lum
authors.forename: Peter
authors.initials: P
authors.lastname: Calhoun
authors.forename: Craig
authors.initials: C
authors.lastname: Kollman
authors.forename: Eyal
authors.initials: E
authors.lastname: Dassau
authors.forename: Anne
authors.initials: A
authors.lastname: Farret
authors.forename: Jerome
authors.initials: J
authors.lastname: Place
authors.forename: Marc
authors.initials: M
authors.lastname: Breton
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Anderson
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Man
authors.forename: Simone
authors.initials: S
authors.lastname: Del Favero
authors.forename: Daniela
authors.initials: D
authors.lastname: Bruttomesso
authors.forename: Alessio
authors.initials: A
authors.lastname: Filippi
authors.forename: Rachele
authors.initials: R
authors.lastname: Scotton
authors.forename: Moshe
authors.initials: M
authors.lastname: Phillip
authors.forename: Eran
authors.initials: E
authors.lastname: Atlas
authors.forename: Ido
authors.initials: I
authors.lastname: Muller
authors.forename: Shahar
authors.initials: S
authors.lastname: Miller
authors.forename: Chiara
authors.initials: C
authors.lastname: Toffanin
authors.forename: Davide Martino
authors.initials: DM
authors.lastname: Raimondo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Nicolao
authors.forename: Roy W
authors.initials: RW
authors.lastname: Beck
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism*; D015190:Blood Glucose Self-Monitoring; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004040:Dietary Carbohydrates; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control*; D007003:Hypoglycemia / Q000097:blood / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D062407:Meals; D008991:Monitoring, Physiologic; D019397:Pancreas, Artificial; D061214:Patient Safety; D010865:Pilot Projects; D019518:Postprandial Period; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human