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Hierarchical Order ...
Hierarchical Order of Distinct Autoantibody Spreading and Progression to Type 1 Diabetes in the TEDDY Study
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- Vehik, Kendra (författare)
- University of South Florida
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- Bonifacio, Ezio (författare)
- Dresden University of Technology
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- Lernmark, Ake (författare)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital
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- Yu, Liping (författare)
- University of Colorado-Denver
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- Williams, Alistair (författare)
- University of Bristol
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- Schatz, Desmond (författare)
- University of Florida
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- Rewers, Marian (författare)
- University of Colorado-Denver
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- She, Jin-Xiong (författare)
- Medical College of Georgia
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- Toppari, Jorma (författare)
- Turku University Hospital
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- Hagopian, William (författare)
- Pacific Northwest Research Institute
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- Akolkar, Beena (författare)
- National Institute of Diabetes and Digestive and Kidney Diseases
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- Ziegler, Anette G (författare)
- Technical University of Munich
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- Krischer, Jeffrey P (författare)
- University of South Florida
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(creator_code:org_t)
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- 2020-07-08
- 2020
- Engelska.
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:9, s. 2066-2073
- Relaterad länk:
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http://dx.doi.org/10...
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https://care.diabete...
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https://lup.lub.lu.s...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- 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 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 IA2 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Vehik, Kendra
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Bonifacio, Ezio
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Lernmark, Ake
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Yu, Liping
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Williams, Alista ...
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Schatz, Desmond
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Rewers, Marian
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She, Jin-Xiong
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Toppari, Jorma
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Hagopian, Willia ...
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Akolkar, Beena
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Ziegler, Anette ...
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Krischer, Jeffre ...
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- MEDICIN OCH HÄLSOVETENSKAP
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och Klinisk medicin
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Diabetes Care
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Lunds universitet