Glucometabolic Control and Anti-Transglutaminase Antibodies at Celiac Disease Onset in Type 1 Diabetes Youth

Context: Anti-transglutaminase antibodies (anti-TTG IgA) titer is associated with mucosal damage in celiac disease (CD). Objective: The primary focus was to correlate anti-TTG IgA titer, HbA1c when CD occurs (HbA1cCD), and Marsh grade in children and adolescents with type 1 diabetes (T1D) at the time of CD diagnosis. As secondary outcomes, we assessed the optimal anti-TTG IgA upper limit of normal (ULN) cutoff for sparing biopsy, and personal and familial autoimmunity history in the individuals with T1D and CD (T1D-CD) compared with T1D-only. Methods: In this retrospective observational study, among 6933 individuals with T1D onset (2010-2019), 556 were grouped according to CD onset: before (CD_FIRST), concomitant (CD_CONCOMITANT), or after T1D (T1D_FIRST), and compared with 141 T1D without CD. Measures included HbA1cCD, fold-anti-TTG IgA, anti-TTG IgA cutoff, and autoimmunity history of both groups, as well as Marsh grade in T1D-CD. Results: In youths with T1D, HbA1cCD was associated with increased fold-anti-TTG IgA (Spearman r = 0.14, P = .0047). The optimal anti-TTG IgA cutoff for sparing biopsy was 11 ULN. Autoimmunity was prevalent in T1D-CD individuals, who showed more comorbidities than controls (χ2 25.4, P < .001), particularly the CD_FIRST (P < .001). Conclusion: In children with T1D-CD, worse glucometabolic control is associated with an increase in fold anti-TTG IgA and with worse Marsh grade. A slightly higher anti-TTG IgA cutoff may be necessary for sparing biopsy compared to children in the general population. Higher prevalence of autoimmune comorbidities in CD_FIRST suggests that screening for T1D in the CD population should be mandatory.