Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes

Abstract

Aim: Screening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed.

Methods: This was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis.

Results: Of 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA_1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period.

Conclusions: Our study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.

Keywords: Autoimmune disease; Coeliac disease; Gluten; Polyendocrinopathy; Screening; Type 1 diabetes.

Fig. 1

Selection of the study population. Inclusion criteria were diagnosis of type 1 diabetes between 1995 and June 2021, age between 6 months and 18 years at diagnosis, available baseline anti-tTGA data within 11 days of diabetes onset, elevated anti-tTGA titres above the ULN according to the reference values of the respective laboratories of the treating centres at diagnosis of diabetes, and biopsy-proven coeliac disease within the first 36 months of diabetes onset

Fig. 2

(a) Proportion of children and adolescents with new-onset type 1 diabetes screened for antibodies against tTGA at the onset of type 1 diabetes and (b) proportion who underwent histological examination for coeliac disease after a positive screening result from 2001 onwards. Error bars indicate 95% CIs

Fig. 3

SDS values for (a) height and (b) BMI for participants with early vs delayed biopsy-proven coeliac disease. Error bars indicate 95% CIs. SDS values are shown at diagnosis of type 1 diabetes (n = 409 for both), at biopsy (n = 279 and 277, respectively), 2 years after biopsy (n = 365 for both) and at the last follow-up (n=409 for both; median diabetes duration 5.3 years and 5.1 years for the early and delayed biopsy groups, respectively)