Challenge of diagnosing celiac disease in pediatric type 1 diabetes mellitus: lessons from long-term serological surveillance

OBJECTIVES: Children with type 1 diabetes mellitus (T1DM) have an increased risk of developing celiac disease (CD), frequently without typical symptoms. However, the optimal screening strategies and diagnostic threshold for tissue transglutaminase antibody immunoglobulin A (tTG-IgA) remain controversial. This study aimed to assess the performance of CD screening tests and identify optimal serological thresholds in children with T1DM. METHODS: This 12-year retrospective single-center cohort study from Türkiye included 282 newly diagnosed T1DM children without prior CD. Patients with <2 CD screenings performed ≥ 6 months apart or incomplete records were excluded. Among the remaining cohort, 206 patients had longitudinal screening for CD. Of them, only 24 patients who had seropositivity constituted the main analytical sample for assessing the diagnostic performance of tTG-IgA levels using receiver operating characteristic (ROC) analysis. RESULTS: Among the 206 patients with longitudinal CD screening, tTG-IgA positivity was observed in 24 patients (11.6%), either at T1DM diagnosis (70.8%) or during follow-up (29.2%). Biopsy-confirmed CD was diagnosed in 4.8% of the cohort. The remaining patients had fluctuations in tTG-IgA level; 50% became seronegative, but two-thirds became positive again. ROC analysis identified an optimal tTG-IgA threshold of ≥7.3× the upper limit of normal (ULN), yielding an area under the curve of 0.81, sensitivity of 70%, and specificity of 100%. Notably, 8.3% of biopsy-confirmed CD cases had tTG-IgA levels < 3×ULN. CONCLUSION: Although tTG-IgA level ≥7.3×ULN is highly predictive of CD in children with T1DM, lower levels may also be noteworthy. Continuous long-term monitoring and a multi-dimensional approach are crucial for early and accurate CD diagnosis in this high-risk group.