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首页> 外文期刊>Diabetes care >Hierarchical Order of Distinct Autoantibody Spreading and Progression to Type 1 Diabetes in the TEDDY Study
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Hierarchical Order of Distinct Autoantibody Spreading and Progression to Type 1 Diabetes in the TEDDY Study

机译：不同自身抗体传播和进展的分层顺序，在泰迪研究中为1型糖尿病

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摘要

OBJECTIVE The first-appearing beta-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.
机译：目的已被证明第一出现的β细胞自身抗体影响1型糖尿病（T1D）的风险。在这里，我们评估了自身抗体蔓延到二次出现的自身抗体和进一步进展的年轻（TEDDY）研究中的糖尿病环境决定因素的进一步进展。研究设计和方法HLA-DR-DQ遗传风险的符合条件的儿童T1D的季节性季度从3个月内季度从3个月内遵循高达15年的开发，用于开发单一出现的自身抗体（GAD抗体[Gada]，胰岛素自身抗体[IAA]，或胰岛素抗原-2自身抗体[IA-2A]）和随后开发单一的第二次出现的自身抗体和进展至T1D。在两次实验室确认的两个连续访问中，将自身抗体阳性定义为特异性自身抗体的阳性。在开发另一个自身抗体的儿童中测量锌转运蛋白80Acorantibody（ZnT8A）。结果有608名儿童开发了一个单一的先出现自身抗体（IAA，N = 282或Gada，N = 326），从出生后12.5岁的中位随访。二次出现的自身抗体的风险独立于GADA与IAA作为第一出现的自身抗体（调整后危险比[HR] 1.12; 95％CI 0.88-1.42; P = 0.36）。与单一自身抗体，例如IAA或GADA持持持态度的儿童相比，二次出现的GADA，IAA，IA-2A或ZNT8A赋予T1D的风险增加，例如，IAA或GRADADA第二（调整为6.44; 95％CI 3.78-10.98），IA -2a秒（调整后的HR 16.33; 95％CI 9.10-29.29; p <0.0001），或ZnT8a秒（调整后的HR 5.35; 95％CI 2.61-10.95; P <0.0001）。在开发出一个不同的第二个自身抗体的儿童IA-2A（调整后的HR 3.08; 95％CI 2.04-4.65; P <0.0001）与GADA或IAA相比，赋予T1D的更大风险。此外，血清转换的年轻初始年龄和第二出现自身抗体的开发的更短的时间增加了T1D的风险。结论不同自身抗体蔓延的分层顺序与先出现的自身抗体类型无关，并且年龄依赖性并增强进展的风险。

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  • 来源
    《Diabetes care》 |2020年第9期|共8页
  • 作者

    Vehik Kendra; Bonifacio Ezio; Lernmark Ake; Yu Liping; Williams Alistair; Schatz Desmond; Rewers Marian; She Jin-Xiong; Toppari Jorma; Hagopian William; Akolkar Beena; Ziegler Anette G.; Krischer Jeffrey P.;

  • 作者单位

    Univ S Florida Morsani Coll Med Hlth Informat Inst Tampa FL 33620 USA;

    Helmholtz Zentrum Munchen Forschergrp Diabet eV German Res Ctr Environm Hlth Munich Germany;

    Lund Univ Dept Clin Sci CRC Skane Univ Hosp Malmo Sweden;

    Univ Colorado Barbara Davis Ctr Childhood Diabet Aurora CO USA;

    Univ Bristol Diabet &

    Metab Translat Hlth Sci Bristol Avon England;

    Univ Florida Diabet Ctr Excellence Gainesville FL USA;

    Univ Colorado Barbara Davis Ctr Childhood Diabet Aurora CO USA;

    Augusta Univ Ctr Biotechnol &

    Genom Med Augusta GA USA;

    Univ Turku Res Ctr Integrat Physiol &

    Pharmacol Inst Biomed Turku Finland;

    Pacific Northwest Diabet Res Inst Seattle WA USA;

    NIDDK Bethesda MD 20892 USA;

    Helmholtz Zentrum Munchen Forschergrp Diabet eV German Res Ctr Environm Hlth Munich Germany;

    Univ S Florida Morsani Coll Med Hlth Informat Inst Tampa FL 33620 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
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