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Time-resolved autoantibody profiling facilitates stratification of preclinical type 1 diabetes in children

, ; Endesfelder, David; zu Castell, Wolfgang; Bonifacio, Ezio; Rewers, Marian; Hagopian, William A.; She, Jin Xiong; Lernmark, Ake LU ; Toppari, Jorma and Vehik, Kendra LU , et al. (2019) In Diabetes 68(1). p.119-130
Abstract

Progression to clinical type 1 diabetes varies among children who develop b-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar profiles associated with various types of progression among 600 children from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study; these children developed persistent insulin autoantibodies (IAA), GAD autoantibodies (GADA), insulinoma-associated antigen 2 autoantibodies (IA-2A), or a combination of these, and they were followed up prospectively at 3- to 6-month intervals (median follow-up 6.5... (More)

Progression to clinical type 1 diabetes varies among children who develop b-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar profiles associated with various types of progression among 600 children from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study; these children developed persistent insulin autoantibodies (IAA), GAD autoantibodies (GADA), insulinoma-associated antigen 2 autoantibodies (IA-2A), or a combination of these, and they were followed up prospectively at 3- to 6-month intervals (median follow-up 6.5 years). Children who developed multiple autoantibody types (n = 370) were clustered, and progression from seroconversion to clinical diabetes within 5 years ranged between clusters from 6% (95% CI 0, 17.4) to 84% (59.2, 93.6). Children who seroconverted early in life (median age <2 years) and developed IAA and IA-2A that were stable-positive on follow-up had the highest risk of diabetes, and this risk was unaffected by GADA status. Clusters of children who lacked stable-positive GADA responses contained more boys and lower frequencies of the HLA-DR3 allele. Our novel algorithm allows refined grouping of b-cell autoantibody–positive children who distinctly progressed to clinical type 1 diabetes, and it provides new opportunities in searching for etiological factors and elucidating complex disease mechanisms.

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publication status
published
subject
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Diabetes
volume
68
issue
1
pages
12 pages
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85058886151
ISSN
0012-1797
DOI
10.2337/db18-0594
language
English
LU publication?
yes
id
cb69de7b-cbad-434d-8667-537a2aca4cf6
date added to LUP
2019-01-03 08:14:45
date last changed
2019-05-21 04:16:52
@article{cb69de7b-cbad-434d-8667-537a2aca4cf6,
  abstract     = {<p>Progression to clinical type 1 diabetes varies among children who develop b-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar profiles associated with various types of progression among 600 children from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study; these children developed persistent insulin autoantibodies (IAA), GAD autoantibodies (GADA), insulinoma-associated antigen 2 autoantibodies (IA-2A), or a combination of these, and they were followed up prospectively at 3- to 6-month intervals (median follow-up 6.5 years). Children who developed multiple autoantibody types (n = 370) were clustered, and progression from seroconversion to clinical diabetes within 5 years ranged between clusters from 6% (95% CI 0, 17.4) to 84% (59.2, 93.6). Children who seroconverted early in life (median age &lt;2 years) and developed IAA and IA-2A that were stable-positive on follow-up had the highest risk of diabetes, and this risk was unaffected by GADA status. Clusters of children who lacked stable-positive GADA responses contained more boys and lower frequencies of the HLA-DR3 allele. Our novel algorithm allows refined grouping of b-cell autoantibody–positive children who distinctly progressed to clinical type 1 diabetes, and it provides new opportunities in searching for etiological factors and elucidating complex disease mechanisms.</p>},
  author       = {,  and Endesfelder, David and zu Castell, Wolfgang and Bonifacio, Ezio and Rewers, Marian and Hagopian, William A. and She, Jin Xiong and Lernmark, Ake and Toppari, Jorma and Vehik, Kendra and Williams, Alistair J.K. and Yu, Liping and Akolkar, Beena and Krischer, Jeffrey P. and Ziegler, Anette G. and Achenbach, Peter},
  issn         = {0012-1797},
  language     = {eng},
  number       = {1},
  pages        = {119--130},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Time-resolved autoantibody profiling facilitates stratification of preclinical type 1 diabetes in children},
  url          = {http://dx.doi.org/10.2337/db18-0594},
  volume       = {68},
  year         = {2019},
}