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

for the TEDDY Study Group*

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)119-130
Number of pages12
JournalDiabetes
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2019

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Type 1 Diabetes Mellitus
Autoantibodies
Insulinoma
HLA-DR3 Antigen
Insulin
Antigens
Disease Progression
Cohort Studies
Alleles
Parturition

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Time-resolved autoantibody profiling facilitates stratification of preclinical type 1 diabetes in children. / for the TEDDY Study Group*.

In: Diabetes, Vol. 68, No. 1, 01.01.2019, p. 119-130.

Research output: Contribution to journalArticle

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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 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.",
author = "{for the TEDDY Study Group*} and David Endesfelder and {zu Castell}, Wolfgang and Ezio Bonifacio and Marian Rewers and Hagopian, {William A.} and Jin-Xiong She and Ake Lernmark and Jorma Toppari and Kendra Vehik and Williams, {Alistair J.K.} and Liping Yu and Beena Akolkar and Krischer, {Jeffrey P.} and Ziegler, {Anette G.} and Peter Achenbach",
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AU - for the TEDDY Study Group

AU - Endesfelder, David

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AU - Bonifacio, Ezio

AU - Rewers, Marian

AU - Hagopian, William A.

AU - She, Jin-Xiong

AU - Lernmark, Ake

AU - Toppari, Jorma

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AU - Williams, Alistair J.K.

AU - Yu, Liping

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