A combined risk score enhances prediction of type 1 diabetes among susceptible children

Research output: Contribution to journalArticle


Type 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk1. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common2,3 and is most severe in the very young4,5, in whom it can be life threatening and difficult to treat6-9. Autoantibody surveillance programs effectively prevent most ketoacidosis10-12 but require frequent evaluations whose expense limits public health adoption13. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible14 because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve ≥ 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.


  • L.A. Ferrat
  • K. Vehik
  • S.A. Sharp
  • Å. Lernmark
  • M.J. Rewers
  • J.-X. She
  • A.-G. Ziegler
  • J. Toppari
  • B. Akolkar
  • J.P. Krischer
  • M.N. Weedon
  • R.A. Oram
  • W.A. Hagopian
  • TEDDY Study Group
External organisations
  • University of Exeter
  • University of South Florida
  • Skåne University Hospital
  • University of Colorado
  • Augusta University
  • Helmholtz Zentrum München
  • Klinikum rechts der Isar
  • Turku University Hospital
  • University of Turku
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • Pacific Northwest Diabetes Research Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)1247-1255
Number of pages9
JournalNature Medicine
Issue number8
Publication statusPublished - 2020
Publication categoryResearch