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Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity

William Hagopian1, Hye-Seung Lee2, Edwin Liu3

  • 1Diabetes Programs Division, Pacific Northwest Research Institute, Seattle, Washington; wah@uw.edu.

Pediatrics
|October 12, 2017
PubMed

Insights

Type 1 diabetes (T1D) autoimmunity often appears before celiac disease (CD) autoimmunity in children. Their co-occurrence is higher than expected, suggesting shared environmental or disease mechanisms.

Area of Science:

  • Immunology
  • Pediatrics
  • Genetics

Background:

  • Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune disorders with shared genetic risk factors.
  • Prospective data on the co-occurrence and timing of T1D and CD autoimmunities in early childhood are limited.

Purpose of the Study:

  • To investigate the timing and co-occurrence of T1D and CD autoimmunities in a high-risk birth cohort.
  • To identify genetic and demographic factors associated with the development of both autoimmunities.

Main Methods:

  • A prospective birth cohort study of 8676 children at high genetic risk for T1D and CD, with 5891 analyzed over a median of 66 months.
  • Quarterly evaluation of islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs) from 3 to 48 months of age, followed by semiannual assessments.
  • Analysis of demographic factors, HLA-DR-DQ, HLA-DPB1, and 5 non-HLA genetic loci associated with T1D and CD risk.

Main Results:

  • Of 5891 children, 367 developed IAs alone, 808 developed tTGAs alone, and 90 developed both.
  • The co-occurrence of IAs and tTGAs was significantly higher than expected.
  • IAs typically preceded tTGAs, and preceding IAs increased the risk of subsequent tTGAs (HR: 1.48).
  • Increased co-occurrence was associated with T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94), and SH2B3 rs3184504 (HR: 1.53).

Conclusions:

  • In early childhood, T1D autoimmunity generally precedes CD autoimmunity.
  • The observed co-occurrence of T1D and CD autoimmunities exceeds that explained by known genetic and demographic factors.
  • Shared environmental or pathophysiological mechanisms likely contribute to the increased risk and co-occurrence of these autoimmune diseases.
Abstract

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