Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).

RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.

RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).

CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.

Details

Authors
  • TEDDY Study Group
  • Jeffrey P Krischer
  • Xiang Liu
  • Kendra Vehik
  • Beena Akolkar
  • William A Hagopian
  • Marian J Rewers
  • Jin-Xiong She
  • Jorma Toppari
  • Anette-G Ziegler
  • Åke Lernmark
  • Daniel Agardh (Contributor)
  • Carin Andrén Aronsson (Contributor)
  • Maria Ask (Contributor)
  • Jenny Bremer (Contributor)
  • Emelie Ericson-Hallström (Contributor)
  • Annika Björne Fors (Contributor)
  • Lina Fransson (Contributor)
  • Thomas Gard (Contributor)
  • Rasmus Bennet (Contributor)
  • Susanne Hyberg (Contributor)
  • Hanna Jisser (Contributor)
  • Fredrik Johansen (Contributor)
  • Berglind Jónsdóttir (Contributor)
  • SILVIJA JOVIC (Contributor)
  • Helena Elding Larsson (Contributor)
  • Marielle Lindström (Contributor)
  • Markus Lundgren (Contributor)
  • Maria Månsson Martinez (Contributor)
  • Maria Markan (Contributor)
  • Marie Jessica Melin (Contributor)
  • Zeliha Mestan (Contributor)
  • Caroline N Nilsson (Contributor)
  • Karin Ottosson (Contributor)
  • Kobra Rahmati (Contributor)
  • Anita Ramelius (Contributor)
  • Falastin Salami (Contributor)
  • Anette Sjöberg (Contributor)
  • Birgitta Sjöberg (Contributor)
  • Carina Törn (Contributor)
  • Anne Wallin (Contributor)
  • Åsa Wimar (Contributor)
  • Sofie Åberg (Contributor)
Organisations
External organisations
  • University of South Florida
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • Pacific Northwest Diabetes Research Institute
  • University of Colorado
  • Augusta University
  • University of Turku
  • Turku University Hospital
  • Technical University of Munich
  • Skåne University Hospital
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)1051-1060
Number of pages10
JournalDiabetes Care
Volume42
Issue number6
Publication statusPublished - 2019 Jun
Publication categoryResearch
Peer-reviewedYes