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- Titel:
Hierarchical Order of Distinct Autoantibody Spreading and Progression to Type 1 Diabetes in the TEDDY Study.
- Dokumenttyp:
- Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
- Autor(en):
- Vehik, Kendra; Bonifacio, Ezio; Lernmark, Åke; Yu, Liping; Williams, Alistair; Schatz, Desmond; Rewers, Marian; She, Jin-Xiong; Toppari, Jorma; Hagopian, William; Akolkar, Beena; Ziegler, Anette G; Krischer, Jeffrey P
- Abstract:
- OBJECTIVE: The first-appearing β-cell autoantibody has been shown to influence risk of type 1 diabetes (T1D). Here, we assessed the risk of autoantibody spreading to the second-appearing autoantibody and further progression to clinical disease in The Environmental Determinants of Diabetes in the Young (TEDDY) study. RESEARCH DESIGN AND METHODS: Eligible children with increased HLA-DR-DQ genetic risk for T1D were followed quarterly from age 3 months up to 15 years for development of a single first-appearing autoantibody (GAD antibody [GADA], insulin autoantibody [IAA], or insulinoma antigen-2 autoantibody [IA-2A]) and subsequent development of a single second-appearing autoantibody and progression to T1D. Autoantibody positivity was defined as positivity for a specific autoantibody at two consecutive visits confirmed in two laboratories. Zinc transporter 8 autoantibody (ZnT8A) was measured in children who developed another autoantibody. RESULTS: There were 608 children who developed a single first-appearing autoantibody (IAA, n = 282, or GADA, n = 326) with a median follow-up of 12.5 years from birth. The risk of a second-appearing autoantibody was independent of GADA versus IAA as a first-appearing autoantibody (adjusted hazard ratio [HR] 1.12; 95% CI 0.88-1.42; P = 0.36). Second-appearing GADA, IAA, IA-2A, or ZnT8A conferred an increased risk of T1D compared with children who remained positive for a single autoantibody, e.g., IAA or GADA second (adjusted HR 6.44; 95% CI 3.78-10.98), IA-2A second (adjusted HR 16.33; 95% CI 9.10-29.29; P < 0.0001), or ZnT8A second (adjusted HR 5.35; 95% CI 2.61-10.95; P < 0.0001). In children who developed a distinct second autoantibody, IA-2A (adjusted HR 3.08; 95% CI 2.04-4.65; P < 0.0001) conferred a greater risk of progression to T1D as compared with GADA or IAA. Additionally, both a younger initial age at seroconversion and shorter time to the development of the second-appearing autoantibody increased the risk for T1D. CONCLUSIONS: The hierarchical order of distinct autoantibody spreading was independent of the first-appearing autoantibody type and was age-dependent and augmented the risk of progression to T1D.
- Zeitschriftentitel:
- Diabetes Care
- Jahr:
- 2020
- Band / Volume:
- 43
- Heft / Issue:
- 9
- Seitenangaben Beitrag:
- 2066-2073
- Volltext / DOI:
- doi:10.2337/dc19-2547
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/32641373
- Print-ISSN:
- 0149-5992
- TUM Einrichtung:
- Klinik und Poliklinik für Kinderheilkunde und Jugendmedizin
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