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

Krischer, Jeffrey P.; Lynch, Kristian F.; Schatz, Desmond A.; Ilonen, Jorma; Lernmark, Åke LU ; Hagopian, William A.; Rewers, Marian J.; She, Jin-Xiong; Simell, Olli G. and Toppari, Jorma, et al. (2015) In Diabetologia 58(5). p.980-987
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... (More)
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. (Less)
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published
subject
keywords
Autoimmunity, Diabetes in young children, HLA-DR-DQ genotypes, Incidence, Islet autoantibodies, Type 1 diabetes
in
Diabetologia
volume
58
issue
5
pages
980 - 987
publisher
Springer Verlag
external identifiers
  • wos:000352644200014
  • scopus:84939961476
ISSN
1432-0428
DOI
10.1007/s00125-015-3514-y
language
English
LU publication?
yes
id
52e1c761-60b9-47e4-a452-0c3f8d93536e (old id 5386046)
date added to LUP
2015-06-01 09:26:51
date last changed
2017-11-12 03:01:01
@article{52e1c761-60b9-47e4-a452-0c3f8d93536e,
  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.},
  author       = {Krischer, Jeffrey P. and Lynch, Kristian F. and Schatz, Desmond A. and Ilonen, Jorma and Lernmark, Åke and Hagopian, William A. and Rewers, Marian J. and She, Jin-Xiong and Simell, Olli G. and Toppari, Jorma and Ziegler, Anette-G. and Akolkar, Beena and Bonifacio, Ezio},
  issn         = {1432-0428},
  keyword      = {Autoimmunity,Diabetes in young children,HLA-DR-DQ genotypes,Incidence,Islet autoantibodies,Type 1 diabetes},
  language     = {eng},
  number       = {5},
  pages        = {980--987},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study},
  url          = {http://dx.doi.org/10.1007/s00125-015-3514-y},
  volume       = {58},
  year         = {2015},
}