title: The potential for improvement of outcomes by personalized insulin treatment of type 1 diabetes as assessed by analysis of single-patient data from a randomized controlled cross-over insulin trial.
abstract: OBJECTIVE
  The evidence for optimal insulin treatment in type 1 diabetes is mainly based on randomised controlled trials applying a parallel-group design. Such trials yield robust general results but crucial individual treatment effects cannot be extracted. We aimed to assess the potential for further improvement of outcomes by personalized insulin therapy by analyzing data from a cross-over trial at individual level.
  
  
  METHODS
  Post hoc analysis of data from a two-year multicentre, prospective, randomised, open, blinded endpoint (PROBE) trial (the HypoAna trial). In a cross-over design 114 patients with type 1 diabetes and recurrent severe hypoglycemia were treated with basal-bolus therapy based on analog (detemir/aspart) or human (NPH/regular) insulin aiming at maintenance of baseline HbA1c levels. For each patient a superior outcome was defined as fewer events of severe hypoglycemia defined by need for third party treatment assistance or a more than 0.4% (4.4mmol/mol) lower HbA1c.
  
  
  RESULTS
  Only one quarter had comparable outcome of the two treatments in terms of rate of severe hypoglycemia or HbA1c. Twice as many patients had superior outcome of analog-based as compared to human insulin-based insulin treatment. The rate of severe hypoglycemia with the superior treatment was lower compared to the rates obtained with analog insulin and with human insulin (0.67, 1.09, and 1.57 episode per patient-year, respectively (p<0.0001)).
  
  
  CONCLUSIONS
  Personalized insulin treatment of type 1 diabetes based on single-patient evidence may improve outcomes significantly compared to a general treatment approach.
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital, Hillerød, Denmark; Faculties of Health Sciences, University of Copenhagen, Denmark. Electronic address: ulpebj@noh.regionh.dk.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Pedersen-Bjergaard
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital, Hillerød, Denmark.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Kristensen
authors.affiliation: Department of Endocrinology M, Odense University Hospital, Odense, Denmark; Faculties of Health Sciences, University of Southern Denmark, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.affiliation: Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Nørgaard
authors.affiliation: Department of Internal Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Perrild
authors.affiliation: Department of Endocrinology M, Aarhus University Hospital, Aarhus, Denmark; Faculties of Health Sciences, University of Aarhus, Denmark.
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.affiliation: Department of Medical Endocrinology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Tonny
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Department of Medical Endocrinology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; Faculties of Health Sciences, University of Aarhus, Denmark.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital, Hillerød, Denmark; Faculties of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Birger
authors.initials: B
authors.lastname: Thorsteinsson
authors.affiliation: Department of Clinical Research, Nordsjællands University Hospital, Hillerød, Denmark; Steno Diabetes Center, Gentofte, Denmark; Faculties of Health Sciences, University of Aarhus, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
mesh_terms: D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007003:Hypoglycemia; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007328:Insulin
keywords: HbA1c; Human insulin; Insulin analogs; Personalized therapy; Severe hypoglycemia; Type 1 diabetes