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

Ancillary Studies, Diet, Genetics, Human Subjects/Publicity/Publications, Immune Markers, Infectious Agents, Laboratory Implementation, Maternal Studies, Psychosocial, Quality Assurance, Steering, Study Coordinators, Celiac Disease, Clinical Implementation, TEDDY study group

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1009-1017
Number of pages9
JournalActa Diabetologica
Volume54
Issue number11
DOIs
StatePublished - Nov 1 2017

Keywords

  • Autoantibodies
  • Joint modeling
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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