title: Feasibility of overnight closed-loop therapy in young children with type 1 diabetes aged 3-6 years: comparison between diluted and standard insulin strength.
abstract: OBJECTIVE
  To assess feasibility of overnight closed-loop therapy in young children with type 1 diabetes and contrast closed loop using diluted versus standard insulin strength.
  
  
  METHODS
  Eleven children (male 6; age range 3.75-6.96 years; glycated hemoglobin 60 (14) mmol/mol; body mass index SD score 1.0 (0.8); diabetes duration 2.2 (1.0) years, mean (SD); total daily dose 12.9 (10.6, 16.5) IU/day, median (IQR)) were studied at a clinical research facility on two occasions. In random order, participants received closed loop with diluted insulin aspart (CL_Dil; 20 IU/mL) or closed loop with standard aspart (CL_Std; 100 IU/mL) from 17:00 until 8:00 the following morning. Children consumed an evening meal at 17:00 (44 (12) gCHO) and an optional bedtime snack (6 (7) gCHO) identical on both occasions. Meal insulin boluses were calculated by standard pump bolus calculators. Basal rates on insulin pump were adjusted every 15 min as directed by a model-predictive-control algorithm informed by a real-time glucose sensor values.
  
  
  RESULTS
  Mean plasma glucose was 122 (24) mg/dL during CL_Dil vs 122 (23) mg/dL during CL_Std (p=0.993). The time spent in the target glucose range 70-145 mg/dL was 83 (70, 100)% vs 72 (54, 81)% (p=0.328). Time above 145 mg/dL was 13 (0, 27)% vs 19 (10, 45)% (p=0.477) and time spent below 70 mg/dL was 0.0 (0.0, 1.4)% vs 1.4 (0.0, 11.6)% (p=0.161). One asymptomatic hypoglycemia below 63 mg/dL occurred in one participant during CL_Dil versus six episodes in five participants during CL_Std (p=0.09). Glucose variability measured by CV of plasma glucose tended to be reduced during CL_Dil (20% (13, 31) vs 32% (24, 42), p=0.075).
  
  
  CONCLUSIONS
  In this feasibility study, closed-loop therapy maintained good overnight glucose control with tendency towards reduced hypoglycemia and reduced glucose variability using diluted insulin.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01557634.
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Elleri
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Allen
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Tauschmann
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: Ranna
authors.initials: R
authors.lastname: El-Khairi
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK ; Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead , Sydney , Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Benitez-Aguirre
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Acerini
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.affiliation: Department of Paediatrics , Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge , Cambridge , UK.
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
keywords: Artificial Pancreas; Child; Type 1