Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Andreas Weiss - , German Center for Diabetes Research, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Jose Zapardiel-Gonzalo - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Franziska Voss - , Helmholtz Centre for Environmental Research (Author)
  • Manja Jolink - , Helmholtz Centre for Environmental Research (Author)
  • Joanna Stock - , Helmholtz Centre for Environmental Research (Author)
  • Florian Haupt - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Kerstin Kick - , Technical University of Munich (Author)
  • Tiziana Welzhofer - , Technical University of Munich (Author)
  • Anja Heublein - , Helmholtz Centre for Environmental Research (Author)
  • Christiane Winkler - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research (Author)
  • Peter Achenbach - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)
  • Anette Gabriele Ziegler - , Helmholtz Centre for Environmental Research, German Center for Diabetes Research, Technical University of Munich (Author)
  • Ezio Bonifacio - , Center for Regenerative Therapies Dresden, Chair of Preclinical stem cell therapy and diabetes, German Center for Diabetes Research (Author)

Abstract

Aims/hypothesis: The aim of this study was to develop strategies that identify children from the general population who have late-stage presymptomatic type 1 diabetes and may, therefore, benefit from immune intervention. Methods: We tested children from Bavaria, Germany, aged 1.75–10 years, enrolled in the Fr1da public health screening programme for islet autoantibodies (n=154,462). OGTT and HbA1c were assessed in children with multiple islet autoantibodies for diagnosis of presymptomatic stage 1 (normoglycaemia) or stage 2 (dysglycaemia) type 1 diabetes. Cox proportional hazards and penalised logistic regression of autoantibody, genetic, metabolic and demographic information were used to develop a progression likelihood score to identify children with stage 1 type 1 diabetes who progressed to stage 3 (clinical) type 1 diabetes within 2 years. Results: Of 447 children with multiple islet autoantibodies, 364 (81.4%) were staged. Undiagnosed stage 3 type 1 diabetes, presymptomatic stage 2, and stage 1 type 1 diabetes were detected in 41 (0.027% of screened children), 30 (0.019%) and 293 (0.19%) children, respectively. The 2 year risk for progression to stage 3 type 1 diabetes was 48% (95% CI 34, 58) in children with stage 2 type 1 diabetes (annualised risk, 28%). HbA1c, islet antigen-2 autoantibody positivity and titre, and the 90 min OGTT value were predictors of progression in children with stage 1 type 1 diabetes. The derived progression likelihood score identified substages corresponding to ≤90th centile (stage 1a, n=258) and >90th centile (stage 1b, n=29; 0.019%) of stage 1 children with a 4.1% (95% CI 1.4, 6.7) and 46% (95% CI 21, 63) 2 year risk of progressing to stage 3 type 1 diabetes, respectively. Conclusions/interpretation: Public health screening for islet autoantibodies found 0.027% of children to have undiagnosed clinical type 1 diabetes and 0.038% to have undiagnosed presymptomatic stage 2 or stage 1b type 1 diabetes, with 50% risk to develop clinical type 1 diabetes within 2 years.

Details

Original languageEnglish
Pages (from-to)2121-2131
Number of pages11
JournalDiabetologia
Volume65
Issue number12
Publication statusPublished - 27 Aug 2022
Peer-reviewedYes

External IDs

PubMed 36028774

Keywords

Sustainable Development Goals

Keywords

  • Clinical trial modelling, Glucose tolerance, Immunotherapy, Islet autoantibodies, Population screening, Progression score, Public health screening, Type 1 diabetes, Diabetes Mellitus, Type 1/epidemiology, Public Health, Autoantibodies, Humans, Islets of Langerhans/metabolism, Disease Progression, Mass Screening, Child

Library keywords