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The prevalence of autoimmune diseases in antibody negative type 1 diabetes mellitus

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Published/Copyright: March 16, 2026
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism

Abstract

Objectives

Type 1 diabetes mellitus (T1D) results from autoimmune destruction of pancreatic β cells. T1D individuals face increased risk of autoimmune thyroid disease (AITD) and celiac disease (CD). While most patients present with β-cell autoantibodies, 5–10 % do not and are classified as antibody-negative T1D (AB− T1D). Whether autoimmune disease risk differs between AB− and antibody-positive T1D (AB+ T1D) remains uncertain.

Methods

Children aged 6 months to 18 years diagnosed with T1D between January 2010 and June 2023 were reviewed and categorized as AB+ or AB− based on islet cell antigen, insulin, and GAD-65 autoantibodies at diagnosis. Each AB− patient was matched with two age- and sex-matched AB+ controls within the diagnosis date. Chi-square testing compared CD and AITD prevalence between groups, with significance set p<0.05.

Results

The study included 149 AB− and 298 AB+ subjects. CD prevalence was 5.0 % in the AB+ group and 3.4 % in the AB− group. AITD prevalence was 4.4 % in the AB+ group and 2.7 % in the AB− group. No significant differences were identified. A combined diagnosis of CD and AITD occurred only in the AB+ group (2.2 %, p=0.024). At diagnosis, AB+ patients had higher glucose and beta-hydroxybutyrate levels and lower C-peptide, while venous pH was similar.

Conclusions

AITD and CD prevalence did not differ significantly between AB− and AB+ children with T1D, though coexistence of both conditions occurred only in AB+ patients. These findings suggest that AB− T1D may still involve autoimmunity and support similar surveillance strategies for autoimmune diseases in both groups.

Keywords: type 1 diabetes; idiopathic T1D; autoimmune diseases; celiac disease; autoimmune thyroid disease
Corresponding author: Shadi Bakjaji, MD, Division of Endocrinology, Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA; Assistant Professor of Pediatrics, Division of Pediatric Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Missouri, Columbia, MO, USA; and Mailing address: 2905 Cromford Mill Dr, Columbia, MO, 65203, USA, E-mail:

Acknowledgments

The authors would like to express their gratitude and special thanks to the research and clinical teams at Nationwide Children’s Hospital for their support and dedication to improving the care of children with T1D.

  1. Research ethics: This study was performed in accordance with the Declaration of Helsinki. This human study was approved by the Institutional Review Board (IRB) of Nationwide Children’s Hospital – approval: STUDY00003548.

  2. Informed consent: Parent, guardian, or next of kin consent was not required for the minors because, given the retrospective nature of the study, the requirement for informed consent was waived by the IRB of Nationwide Children’s Hospital.

  3. Author contributions: S.B., A.L., L.M., and R.P.H. contributed to the study design, data collection, and analysis. S.B. drafted the manuscript, while A.L., L.M., and R.P.H. critically reviewed and revised the manuscript. All authors provided substantial input, approved the final version, and agreed to be accountable for all aspects of the work.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: All relevant data generated or analyzed during this study are included in the manuscript. Additional data that support the findings of this study are not publicly available due to institutional privacy policies but may be obtained from the corresponding author upon reasonable request.

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Received: 2025-12-12
Accepted: 2026-02-02
Published Online: 2026-03-16

© 2026 Walter de Gruyter GmbH, Berlin/Boston

https://doi.org/10.1515/jpem-2025-0705
Keywords for this article
type 1 diabetes; idiopathic T1D; autoimmune diseases; celiac disease; autoimmune thyroid disease
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