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Reversion of β-cell autoimmunity changes risk of type 1 diabetes : TEDDY study

Vehik, Kendra LU ; Lynch, Kristian F. LU ; Schatz, Desmond A.; Akolkar, Beena; Hagopian, William; Rewers, Marian; She, Jin Xiong; Simell, Olli; Toppari, Jorma and Ziegle, Anette G., et al. (2016) In Diabetes Care 39(9). p.1535-1542
Abstract

OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of... (More)

OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (<1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.

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published
subject
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Diabetes Care
volume
39
issue
9
pages
8 pages
publisher
American Diabetes Association
external identifiers
  • scopus:84986211384
  • wos:000383663000021
ISSN
0149-5992
DOI
10.2337/dc16-0181
language
English
LU publication?
yes
id
c77a1489-bb84-4145-bf3d-2ffb32950761
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001144/
date added to LUP
2016-12-13 10:30:46
date last changed
2017-10-29 04:55:31
@article{c77a1489-bb84-4145-bf3d-2ffb32950761,
  abstract     = {<p>OBJECTIVE β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (&lt;1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.</p>},
  author       = {Vehik, Kendra and Lynch, Kristian F. and Schatz, Desmond A. and Akolkar, Beena and Hagopian, William and Rewers, Marian and She, Jin Xiong and Simell, Olli and Toppari, Jorma and Ziegle, Anette G. and Lernmark, Åke and Bonifacio, Ezio and Krischer, Jeffrey P.},
  issn         = {0149-5992},
  language     = {eng},
  month        = {09},
  number       = {9},
  pages        = {1535--1542},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {Reversion of β-cell autoimmunity changes risk of type 1 diabetes : TEDDY study},
  url          = {http://dx.doi.org/10.2337/dc16-0181},
  volume       = {39},
  year         = {2016},
}