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Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes

Eising, Stefanie; Ramelius, Anita LU ; Carstensen, Bendix; Hougaard, David M.; Norgaard-Pedersen, Bent; Nerup, Jorn; Lernmark, Åke LU and Pociot, Flemming (2011) In European Journal of Endocrinology 164(2). p.247-252
Abstract
Objective: A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes. Design and methods: The design was an individually matched case-control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981-2002 birth cohorts and stored at -25 degrees C were identified from 2023 patients and from two matched controls (n=4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a... (More)
Objective: A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes. Design and methods: The design was an individually matched case-control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981-2002 birth cohorts and stored at -25 degrees C were identified from 2023 patients and from two matched controls (n=4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1 alleles were analyzed by PCR using time-resolved fluorescence. Results: GAD65A and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%) controls resulting in a hazard ratio (HR) of 7.49 (P<0.0001). The HR decreased to 4.55 but remained significant (P<0.0003) after controlling for parental diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a HR of 2.55 (P<0.0001) for every tenfold increase in the levels of GAD65A and IA-2A. This HR decreased to 1.93 but remained significant (P<0.001) after controlling for parental diabetes and HLA-DQB1 alleles. Conclusion: These data suggest that GAD65A and IA-2A positivity at birth are associated with an increased risk of developing type 1 diabetes in Danish children diagnosed between 1981 and 2004. European Journal of Endocrinology 164 247-252 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Endocrinology
volume
164
issue
2
pages
247 - 252
publisher
Society of the European Journal of Endocrinology
external identifiers
  • wos:000286315500013
  • scopus:78751558476
ISSN
1479-683X
DOI
10.1530/EJE-10-0792
language
English
LU publication?
yes
id
660cb4cb-c492-4df1-9ed2-766f0edc4688 (old id 1876160)
date added to LUP
2011-04-04 07:37:11
date last changed
2017-08-13 03:20:08
@article{660cb4cb-c492-4df1-9ed2-766f0edc4688,
  abstract     = {Objective: A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes. Design and methods: The design was an individually matched case-control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981-2002 birth cohorts and stored at -25 degrees C were identified from 2023 patients and from two matched controls (n=4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1 alleles were analyzed by PCR using time-resolved fluorescence. Results: GAD65A and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%) controls resulting in a hazard ratio (HR) of 7.49 (P&lt;0.0001). The HR decreased to 4.55 but remained significant (P&lt;0.0003) after controlling for parental diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a HR of 2.55 (P&lt;0.0001) for every tenfold increase in the levels of GAD65A and IA-2A. This HR decreased to 1.93 but remained significant (P&lt;0.001) after controlling for parental diabetes and HLA-DQB1 alleles. Conclusion: These data suggest that GAD65A and IA-2A positivity at birth are associated with an increased risk of developing type 1 diabetes in Danish children diagnosed between 1981 and 2004. European Journal of Endocrinology 164 247-252},
  author       = {Eising, Stefanie and Ramelius, Anita and Carstensen, Bendix and Hougaard, David M. and Norgaard-Pedersen, Bent and Nerup, Jorn and Lernmark, Åke and Pociot, Flemming},
  issn         = {1479-683X},
  language     = {eng},
  number       = {2},
  pages        = {247--252},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes},
  url          = {http://dx.doi.org/10.1530/EJE-10-0792},
  volume       = {164},
  year         = {2011},
}