Evaluating the Non-Biopsy Approach for Celiac Disease in T1D
Rosaline Mentink, Caroline R. Meijer, Dick Mul, Chantal den Haan, Margreet Wessels
Celiac Disease in Children With Type 1 Diabetes: A Review to Investigate the Non-Biopsy Approach. Pediatrics Open Science. 2025 Jul 11; 1 (3): 1–7.
Children with type 1 diabetes mellitus (T1DM) are at increased risk of developing celiac disease (CeD). Traditionally, diagnosis requires both positive serology and a confirmatory duodenal biopsy. In children without diabetes, a non-biopsy approach—based on tissue transglutaminase IgA (TGA) levels ≥10× the upper limit of normal (ULN) and positive endomysial antibodies (EMA)—is accepted under strict conditions. However, the validity of this approach in children with T1DM remains unclear.
This systematic review examined the evidence for applying the non-biopsy approach in children with T1DM. Searches across six major medical databases identified 17 studies including 9,279 children with T1DM and positive TGA. Of these, 194 children had TGA ≥10×ULN and available biopsy data.
Key findings:
- Sensitivity: Among 194 children with TGA ≥10×ULN who underwent duodenal biopsy, 95.4% showed histological evidence of CeD (Marsh ≥2).
- EMA Data: Only 18 patients across all studies had both TGA ≥10×ULN and EMA positivity reported, limiting generalizability.
- Study Heterogeneity: Variability in diagnostic methods, patient selection, and biopsy protocols introduced bias, preventing pooled analysis.
- Prevalence: The prevalence of biopsy-confirmed CeD among children with T1DM ranged from 1.9% to 11.3% across regions.
- Guideline Context: Both ESPGHAN and ISPAD guidelines currently advise maintaining biopsy-based confirmation in children with T1DM due to limited evidence for a non-biopsy strategy.
Concluding, the authors state
"The available evidence provided by this review is too limited to support a diagnostic procedure for CeD in children with T1DM without duodenal biopsies. We believe that a prospective study with an adequate sample size and laboratory and histology tests according to the ESPGHAN guidelines (including EMA) is mandatory to address the appropriate procedure to diagnose CeD in children with T1DM." -
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