title: Faster insulin action is associated with improved glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy in adults with type 1 diabetes.
abstract: We aimed to evaluate the relationship between insulin pharmacodynamics and glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy. We retrospectively analysed data from a multicentre randomized control trial involving 32 adults with type 1 diabetes receiving day-and-night closed-loop insulin delivery and sensor-augmented pump therapy over 12 weeks. We estimated time-to-peak insulin action (tmax,IA) and insulin sensitivity ( SI) during both interventions, and correlated these with demographic factors and glycaemic outcomes. During both interventions, tmax,IAwas positively correlated with pre- and post-intervention HbA1c (r = 0.50-0.52, P  < .01) and mean glucose (r = 0.45-0.62, P  < .05), and inversely correlated with time sensor glucose, which was in target range 3.9 to 10 mmol/L (r = -0.64 to -0.47, P  < .05). Increased body mass index was associated with higher tmax,Iand lower SI(both P  < .05). During closed-loop insulin delivery, tmax,IAwas positively correlated with glucose variability ( P  < .05). Faster insulin action is associated with improved glycaemic control during closed-loop insulin delivery and sensor-augmented pump therapy.
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Paediatrics, University of Cambridge, Cambridge, UK.
authors.forename: Yue
authors.identifier: 0000-0003-3498-2543
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Diabetes & Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Hood
authors.identifier: 0000-0001-6076-6997
authors.initials: H
authors.lastname: Thabit
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Diabetes & Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Lalantha
authors.initials: L
authors.lastname: Leelarathna
authors.affiliation: Department of Diabetes & Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Hartnell
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Paediatrics, University of Cambridge, Cambridge, UK.
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Paediatrics, University of Cambridge, Cambridge, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Tauschmann
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Dellweg
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Benesch
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Mader
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Manuel
authors.initials: M
authors.lastname: Holzer
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Kojzar
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Diabetes & Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Evans
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Arnolds
authors.affiliation: Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.|Department of Paediatrics, University of Cambridge, Cambridge, UK.
authors.forename: Roman
authors.identifier: 0000-0003-2901-461X
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000328:Adult; D015374:Biosensing Techniques / Q000295:instrumentation* / Q000379:methods; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: 
  CSII
  ; glycaemic control; insulin delivery; insulin pump therapy; pharmacodynamics; type 1 diabetes