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Pediatrics. 2017 Nov;140(5). pii: e20171305. doi: 10.1542/peds.2017-1305. Epub 2017 Oct 10.

Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity.

Author information

1
Diabetes Programs Division, Pacific Northwest Research Institute, Seattle, Washington; wah@uw.edu.
2
Department of Pediatrics, Health Informatics Institute, University of South Florida, Tampa, Florida.
3
Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, Colorado.
4
Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia.
5
Institute of Diabetes Research, Helmholtz Zentrum München, Oberschleißheim, Germany.
6
Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
7
Department of Pediatrics, Turku University Central Hospital, Turku, Finland.
8
Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
9
Children's Hospital of Oakland Research Institute, Oakland, California; and.
10
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

Abstract

BACKGROUND AND OBJECTIVES:

Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.

METHODS:

In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed.

RESULTS:

Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors.

CONCLUSIONS:

In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.

PMID:
29018046
PMCID:
PMC5654393
DOI:
10.1542/peds.2017-1305
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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