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

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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; Carstensen, Bendix; Hougaard, David M.; Norgaard-Pedersen, Bent; Nerup, Jorn; Lernmark, Åke; Pociot, Flemming.

I: European Journal of Endocrinology, Vol. 164, Nr. 2, 2011, s. 247-252.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Eising, Stefanie ; Ramelius, Anita ; Carstensen, Bendix ; Hougaard, David M. ; Norgaard-Pedersen, Bent ; Nerup, Jorn ; Lernmark, Åke ; Pociot, Flemming. / Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes. I: European Journal of Endocrinology. 2011 ; Vol. 164, Nr. 2. s. 247-252.

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TY - JOUR

T1 - Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes

AU - Eising, Stefanie

AU - Ramelius, Anita

AU - Carstensen, Bendix

AU - Hougaard, David M.

AU - Norgaard-Pedersen, Bent

AU - Nerup, Jorn

AU - Lernmark, Åke

AU - Pociot, Flemming

PY - 2011

Y1 - 2011

N2 - 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

AB - 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

U2 - 10.1530/EJE-10-0792

DO - 10.1530/EJE-10-0792

M3 - Article

VL - 164

SP - 247

EP - 252

JO - European Journal of Endocrinology

T2 - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 1479-683X

IS - 2

ER -