Maltoni et al. (1) report a high prevalence (9.8%) of celiac disease (CD) in 2,164 youth with type 1 diabetes from five pediatric diabetes centers in northern Italy. This is considerably higher than in our recent report (3.5%) from three continents (U.K./Austria/Germany, U.S., and Australia) (2) and the pooled prevalence of 5.1% in a systematic review of CD in type 1 diabetes (3). Maltoni et al. propose that their higher rate of CD may be explained by more active screening programs in Italy. We agree that this is likely to be a contributing factor, as previous reports of high rates of coexisting CD and type 1 diabetes in Italy (4) and of CD in the general population may have heightened awareness of CD risk. It is of note, however, that we used a stringent definition of biopsy-proven CD and that a further 2% of youth from the Prospective Diabetes Follow-up Registry (DPV) and the T1D Exchange Clinic Network (T1DX) registry were suspected of having CD on the basis of positive serology but had not undergone small-bowel biopsy.
We read with interest that the diagnosis of CD preceded type 1 diabetes in 19% of case subjects in the Italian study compared with 5.4% in our report. In keeping with Maltoni et al., we did not classify those with positive CD antibodies at diabetes diagnosis as having preexisting CD. A further 46% demonstrated their first CD autoantibody positivity at type 1 diabetes diagnosis in the Italian study compared with 37% within the first year after diagnosis of type 1 diabetes in our report. The contrasting rates prior to diabetes diagnosis imply a higher awareness of CD risk in the general population in Italy, and we speculate that clinicians may be more likely to screen for CD. The lower incidence of type 1 diabetes in Italy compared with the countries represented in our report may also underlie the different prevalence rates of CD overall. While HLA-DQ2 confers risk for both CD and type 1 diabetes, the penetrance of other risk alleles for type 1 diabetes may be lower in the Italian population. Moreover, it is plausible that the impact of environmental factors that initiate and accelerate type 1 diabetes, such as viral infections (5), may vary between these populations. Another putative explanation is differences in exposure to gluten and/or methods of wheat production that may modify the antigenicity of gluten. Finally, neither report provides data on screening frequency after diabetes diagnosis, which likely influences case detection.
The contrasting findings across these populations, along with the observation that CD is diagnosed after more than 2 years of type 1 diabetes duration (in our report, 40%), highlight the importance of regular screening for CD in people with type 1 diabetes.
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Acknowledgments. The authors thank the thousands of patients and families who contributed to these registries/audits and the numerous investigators.
Funding. The DPV is supported through the German Federal Ministry for Education and Research within the Competence Network for Diabetes Mellitus (grant FKZ 01GI1106), which was integrated into the German Center for Diabetes Research (DZD) as of January 2015. The T1DX is supported through The Leona M. and Harry B. Helmsley Charitable Trust. The National Paediatric Diabetes Audit (NPDA) is funded by the Healthcare Quality Improvement Partnership and delivered by the Royal College of Paediatrics and Child Health. The Australasian Diabetes Data Network (ADDN) is supported by The Australian Type 1 Diabetes Clinical Research Network, led by JDRF Australia (grant 17-2011-665), the recipient of Australian Government funding from the Australian Research Council (through a Special Research Initiative) and the Department of Health and Ageing. M.E.C. is a recipient of a National Health and Medical Research Council Practitioner fellowship (APP1045777).
Duality of Interest. R.W.H. holds an equity fund that may contain stock from pharmaceutical companies. No other potential conflicts of interest relevant to this article were reported.
