title: Adjustment of Open-Loop Settings to Improve Closed-Loop Results in Type 1 Diabetes: A Multicenter Randomized Trial.
abstract: BACKGROUND
  Closed-loop control (CLC) relies on an individual's open-loop insulin pump settings to initialize the system. Optimizing open-loop settings before using CLC usually requires significant time and effort.
  
  
  OBJECTIVE
  The objective was to investigate the effects of a one-time algorithmic adjustment of basal rate and insulin to carbohydrate ratio open-loop settings on the performance of CLC.
  
  
  METHODS
  This study reports a multicenter, outpatient, randomized, crossover clinical trial.
  
  
  METHODS
  Thirty-seven adults with type 1 diabetes were enrolled at three clinical sites.
  
  
  METHODS
  Each subject's insulin pump settings were subject to a one-time algorithmic adjustment based on 1 week of open-loop (i.e., home care) data collection. Subjects then underwent two 27-hour periods of CLC in random order with either unchanged (control) or algorithmic adjusted basal rate and carbohydrate ratio settings (adjusted) used to initialize the zone-model predictive control artificial pancreas controller. Subject's followed their usual meal-plan and had an unannounced exercise session.
  
  
  METHODS
  Time in the glucose range was 80-140 mg/dL, compared between both arms.
  
  
  RESULTS
  Thirty-two subjects completed the protocol. Median time in CLC was 25.3 hours. The median time in the 80-140 mg/dl range was similar in both groups (39.7% control, 44.2% adjusted). Subjects in both arms of CLC showed minimal time spent less than 70 mg/dl (median 1.34% and 1.37%, respectively). There were no significant differences more than 140 mg/dL.
  
  
  CONCLUSIONS
  A one-time algorithmic adjustment of open-loop settings did not alter glucose control in a relatively short duration outpatient closed-loop study. The CLC system proved very robust and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either arm.
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Eyal
authors.initials: E
authors.lastname: Dassau
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Sue A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Pinsker
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Yogish C
authors.initials: YC
authors.lastname: Kudva
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Ravi
authors.initials: R
authors.lastname: Gondhalekar
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Steve
authors.initials: S
authors.lastname: Patek
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Dayu
authors.initials: D
authors.lastname: Lv
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Schiavon
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Joon Bok
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Man
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Ling
authors.initials: L
authors.lastname: Hinshaw
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Kristin
authors.initials: K
authors.lastname: Castorino
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Mallad
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Vikash
authors.initials: V
authors.lastname: Dadlani
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Shelly K
authors.initials: SK
authors.lastname: McCrady-Spitzer
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Molly
authors.initials: M
authors.lastname: McElwee-Malloy
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Wakeman
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Bevier
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Paige K
authors.initials: PK
authors.lastname: Bradley
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Boris
authors.initials: B
authors.lastname: Kovatchev
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Howard C
authors.initials: HC
authors.lastname: Zisser
authors.affiliation: Department of Chemical Engineering (E.D., R.G., J.B.L., H.C.Z., F.J.D.), University of California Santa Barbara, Santa Barbara, CA 93106; William Sansum Diabetes Center (E.D., J.E.P., R.G., J.B.L., K.C., W.C.B., P.K.B., H.C.Z., F.J.D.), Santa Barbara, CA 93105; Center for Diabetes Technology (S.A.B., S.P., D.L., M.M.-M., C.A.W., B.K.), University of Virginia, Charlottesville, VA 22904; Endocrine Research Unit (A.B., Y.C.K., L.H., A.M., V.D., S.K.M.-S.), Mayo Clinic, Rochester, MN 55905; and Department of Information Engineering (M.S., D.M., C.C.), University of Padova, 35131 Padua, Italy.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Doyle
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D015190:Blood Glucose Self-Monitoring; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; 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; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin