Young Age at Diagnosis of Type 1 Diabetes Is Associated with the Development of Celiac Disease—Associated Antibodies in Children Living in Newfoundland and Labrador, Canada

Abstract

Objectives: The objectives of this study were to establish the prevalence of positive antibodies to endomysium (EMA) and tissue transglutaminase (tTG) in children with type 1 diabetes living in Newfoundland and Labrador (NL), and to examine clinical features associated with positive antibodies. Methods: Patients were recruited from the pediatric diabetes clinic. One hundred sixty-seven children with type 1 diabetes from the 280 children followed at the clinic were prospectively screened for celiac disease using EMA and tTG. The variables of Irish descent, age at onset of diabetes, duration of diabetes, sex, family history of celiac disease, hemoglobin A1C (A1C), ferritin, gastrointestinal symptoms, and body mass index were compiled for all patients. The group of patients with positive antibodies to EMA and/or tTG was compared to the group with negative antibodies. Results: The prevalence of patients with positive antibodies to EMA and/or tTG was 16.8% (n = 28). One patient had also been previously diagnosed with symptomatic celiac disease. The two statistically significant variables with positive antibodies were an earlier age at onset of diabetes (Mann-Whitney U two-tailed test: mean difference 3.2 years, 95% CI 1.7–4.8 years, p < 0.0001) and longer duration of diabetes (Mann-Whitney U two-tailed test: mean difference 2.9 years, 95% CI 1.3–4.4 years, p < 0.0001). Irish descent was associated with positive antibodies but did not reach statistical significance. On logistic regression analysis performed with these three variables together, only age at onset of diabetes remained significant. Conclusions: There is a high prevalence of celiac disease-associated antibodies in children living in NL with type 1 diabetes. Unlike other clinical features, an earlier age at onset of diabetes was predictive for positive antibodies. As the majority of children with positive antibodies did not have signs or symptoms of celiac disease, routine screening for celiac disease in type 1 diabetes is recommended.

The Screening of Celiac Serology in Pediatric Patients Diagnosed with Type 1 Diabetes Mellitus

“… 8 The rate of EMA or TTG antibody positivity in T1DM patients was found to be 9.8% to 20.6% in different studies, and it was found to be 18.6% (78 patients) in our study. 2 , 9 , 10 In the literature, the rate of spontaneous normalization of antibodies reported by Unal et al 11 was 23.3%, and it was found to be approximately 35.4% in the study by Waisbourd-Zinman et al 12 …”

Influence of Age and Type 1 Diabetes Mellitus on Serological Test for Celiac Disease in Children

“…Since the serological tests became available for screening, studies have shown that patients with T1DM also have positive tests in the absence of CD diagnosis [ 24 25 26 27 ]. In a pediatric study, TTG IgA was found to be transient or to fluctuate in patients with T1DM and became normal when repeated later and most had an infiltrative lesion or entirely normal mucosa upon histological confirmation [ 26 ].…”

“…One of the well-recognized concerns of the serological tests is the positive serology found in individuals who had normal mucosa [ 13 14 ], though in occasional cases, this might be the result of patchy distribution of disease with inadvertent biopsies of normal mucosa, or ‘latent CD’ if patients eventually developed villous atrophy later [ 22 23 ]. This is particularly notable in T1DM patients with a high positive rate of TTG IgA without mucosal villous atrophy [ 24 25 26 27 ]. The TTG IgA antibody is routinely performed to screen children with T1DM diagnosis for CD whether symptomatic or asymptomatic [ 12 28 ].…”

“…In the presence of positive results, upper endoscopy with small bowel biopsy is performed to confirm diagnosis of CD. However, studies have revealed that some of these initial positive serologies with normal mucosa became negative or remained at low levels in repeat tests [ 25 26 29 ] and CD never developed [ 27 30 ]. Liu et al [ 31 ] suggested that the threshold of TTG IgA for screening purposes should be set higher than for clinical diagnosis to avoid unnecessary biopsy.…”