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Joint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes : results from the TEDDY study

  • Meike Köhler
  • Andreas Beyerlein
  • Kendra Vehik
  • Sonja Greven
  • Nikolaus Umlauf
  • Åke Lernmark
  • William A. Hagopian
  • Marian Rewers
  • Jin-Xiong She
  • Jorma Toppari
  • Beena Akolkar
  • Jeffrey P. Krischer
  • Ezio Bonifacio
  • Anette-G Ziegler
Publishing year: 2017-08-30
Language: English
Pages: 1009-1017
Publication/Series: Acta Diabetologica
Volume: 54
Issue: 11
Document type: Journal article
Publisher: Springer

Abstract english

AIMS: The onset of clinical type 1 diabetes (T1D) is preceded by the occurrence of disease-specific autoantibodies. The level of autoantibody titers is known to be associated with progression time from the first emergence of autoantibodies to the onset of clinical symptoms, but detailed analyses of this complex relationship are lacking. We aimed to fill this gap by applying advanced statistical models.

METHODS: We investigated data of 613 children from the prospective TEDDY study who were persistent positive for IAA, GADA and/or IA2A autoantibodies. We used a novel approach of Bayesian joint modeling of longitudinal and survival data to assess the potentially time- and covariate-dependent association between the longitudinal autoantibody titers and progression time to T1D.

RESULTS: For all autoantibodies we observed a positive association between the titers and the T1D progression risk. This association was estimated as time-constant for IA2A, but decreased over time for IAA and GADA. For example the hazard ratio [95% credibility interval] for IAA (per transformed unit) was 3.38 [2.66, 4.38] at 6 months after seroconversion, and 2.02 [1.55, 2.68] at 36 months after seroconversion.

CONCLUSIONS: These findings indicate that T1D progression risk stratification based on autoantibody titers should focus on time points early after seroconversion. Joint modeling techniques allow for new insights into these associations.


  • Endocrinology and Diabetes
  • Journal Article


  • Diabetes and Celiac Unit
  • ISSN: 1432-5233
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