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Time-resolved autoantibody profiling facilitates stratification of preclinical type 1 diabetes in children

  • David Endesfelder
  • Wolfgang zu Castell
  • Ezio Bonifacio
  • Marian Rewers
  • William A. Hagopian
  • Jin Xiong She
  • Ake Lernmark
  • Jorma Toppari
  • Kendra Vehik
  • Alistair J.K. Williams
  • Liping Yu
  • Beena Akolkar
  • Jeffrey P. Krischer
  • Anette G. Ziegler
  • Peter Achenbach
Publishing year: 2019
Language: English
Pages: 119-130
Publication/Series: Diabetes
Volume: 68
Issue: 1
Document type: Journal article
Publisher: American Diabetes Association Inc.

Abstract english

Progression to clinical type 1 diabetes varies among children who develop b-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar profiles associated with various types of progression among 600 children from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study; these children developed persistent insulin autoantibodies (IAA), GAD autoantibodies (GADA), insulinoma-associated antigen 2 autoantibodies (IA-2A), or a combination of these, and they were followed up prospectively at 3- to 6-month intervals (median follow-up 6.5 years). Children who developed multiple autoantibody types (n = 370) were clustered, and progression from seroconversion to clinical diabetes within 5 years ranged between clusters from 6% (95% CI 0, 17.4) to 84% (59.2, 93.6). Children who seroconverted early in life (median age <2 years) and developed IAA and IA-2A that were stable-positive on follow-up had the highest risk of diabetes, and this risk was unaffected by GADA status. Clusters of children who lacked stable-positive GADA responses contained more boys and lower frequencies of the HLA-DR3 allele. Our novel algorithm allows refined grouping of b-cell autoantibody–positive children who distinctly progressed to clinical type 1 diabetes, and it provides new opportunities in searching for etiological factors and elucidating complex disease mechanisms.


  • Endocrinology and Diabetes


  • Diabetes and Celiac Unit
  • ISSN: 0012-1797
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79


Jan Waldenströms gata 35, Malmö


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00