Predictors of Progression to Villous Atrophy in Children with Type 1 Diabetes and Potential Celiac Disease

Children with type 1 diabetes (T1DM) and positive celiac serology but normal duodenal mucosa (potential celiac disease-CeD) often have spontaneous normalization of serology despite a gluten-containing diet. This results in either repeated biopsies or an upfront advice for gluten-free diet (GFD) if TTG is >10ULN.

To find the predictors of villous atrophy in children with T1DM and potential CeD.

Ambispective observational study: Children with T1DM and potential CeD on a gluten-containing diet were included. Clinical, serological, histological, and immunohistochemical parameters at baseline and follow-up biopsy were evaluated.

Of the 110 children with T1DM and positive celiac serology, 66 (60%) were potential CeD. Forty-three children had follow-up and repeat biopsy after a median of 12 months; 10 (23%) developed villous atrophy (VA), 16 (37%) remained potential CeD, and 17 (40%) had spontaneous normalization of serology. Children who developed VA had higher baseline counts of intraepithelial lymphocytes (IELs), γδ T cells, and CD3 T cells. In multivariate analysis, the baseline γδ T cell/CD3 T cell ratio was an independent predictor of progression to VA (OR 1.15; 95%CI 1.03-1.28; p=0.011; AUROC 0.918). Spontaneous normalization/reduction of TTG-IgA to < 5ULN was associated with reduced risk of VA (OR 0.007, 95%CI 0.00007-0.617; p = 0.030); Combined AUROC for both was 0.972. VA developed in only 26% (6/23) with TTG ≥10 ULN at baseline.

Most children with T1DM and positive celiac serology do not progress to VA; initiating a GFD without biopsy solely on the basis of TTG>10ULN may be unjustified. Baseline elevation in γδ T-cells/CD3 T cell ratio and persistently high serological titres help identify the risk of progression to VA.