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Published in: Diabetologia 5/2015

01-05-2015 | Article

The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study

Authors: Jeffrey P. Krischer, Kristian F. Lynch, Desmond A. Schatz, Jorma Ilonen, Åke Lernmark, William A. Hagopian, Marian J. Rewers, Jin-Xiong She, Olli G. Simell, Jorma Toppari, Anette-G. Ziegler, Beena Akolkar, Ezio Bonifacio, the TEDDY Study Group

Published in: Diabetologia | Issue 5/2015

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Abstract

Aims/hypothesis

Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both.

Methods

Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter.

Results

Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children.

Conclusions/interpretation

Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.
Appendix
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Metadata
Title
The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study
Authors
Jeffrey P. Krischer
Kristian F. Lynch
Desmond A. Schatz
Jorma Ilonen
Åke Lernmark
William A. Hagopian
Marian J. Rewers
Jin-Xiong She
Olli G. Simell
Jorma Toppari
Anette-G. Ziegler
Beena Akolkar
Ezio Bonifacio
the TEDDY Study Group
Publication date
01-05-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 5/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3514-y

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