Clinical and Immunological Features of Celiac Disease in Patients With Type 1 Diabetes Mellitus

Umberto Volta; Francesco Tovoli; Giacomo Caio

Disclosures

Expert Rev Gastroenterol Hepatol. 2011;5(4):479-487. 

In This Article

Serological Screening for CD in T1DM

Since no serological marker shows an absolute (100%) sensitivity and specificity for CD, small intestinal biopsy still remains the 'gold standard' for the diagnosis of gluten-sensitive enteropathy.[39] However, the importance of antibody tests in the diagnostic work-up of CD is more and more relevant, particularly in the setting of T1DM, where a high percentage of patients suffer from an asymptomatic, and for this reason unpredictable, CD.[40] Positivity for CD-related antibodies allows the identification of T1DM patients with suspected CD who must undergo duodenal biopsy to confirm the diagnosis. tTGA of IgA class display the highest sensitivity, allowing the identification of approximately 98% of T1DM patients with untreated CD, but their specificity is slightly disappointing in this setting with a false positive rate of at least 10%, particularly for tTGA cases positive at a very low titer (<two-times the upper normal limit [UNL]) at the onset of T1DM.[18] Although slightly less sensitive (95%), antiendomysial antibodies (EmA) of IgA class show a higher diagnostic accuracy for identifying cases of suspected CD in the T1DM group, since their specificity appears to be almost always absolute in these patients. However, a fluctuating positivity for IgA EmA at a very low titer (<1:20) has been described very rarely at the onset of T1DM.[18] The relevance of antigliadin antibodies (AGAs) for CD diagnosis in T1DM is very poor, since their specificity for both IgA and IgG antibodies is very low, with a high number of false positives at the beginning of T1DM.[41] AGAs have been recently replaced in the diagnostic work-up of CD by deamidated gliadin peptide antibodies (DGP-AGA), whose usefulness for CD screening in T1DM must be still validated.[42] DGP-AGA of IgG class are a highly valuable tool for detecting CD in cases with an associated IgA deficiency.[40] In this clinical setting, tTGA of IgG class also proved their usefulness, being able to identify the majority of CD patients lacking serum IgA.[43]

The serological work-up that can be adopted for CD screening in T1DM is reported in Figure 1. On the basis of antibody results, intestinal biopsy should be directly performed in all T1DM cases with IgA tTGA at a high titer (>two-times UNL), whereas in the case of positivity for tTGA at a low titer (<two-times UNL), a confirmatory IgA EmA-positive test is necessary before proceeding with intestinal biopsy. A transient and fluctuating positivity for CD-related antibody markers at very low titer has been reported in some patients with T1DM at onset with disappearance of these antibodies within a few months.[18] Recent data have clearly shown that high titers of IgA tTGA (>ten-times UNL) are always an expression of CD, whereas low antibody titers (<two to three-times UNL) can be also found in patients with disorders other than CD.[44] Moreover, intestinal biopsy must be always performed in T1DM patients with highly suggestive symptoms for CD even in the case of serological negativity.

Figure 1.

Screening for celiac disease in patients with Type 1 diabetes mellitus.
IgG deamidated gliadin antibodies should be used as a screening test for detecting CD in T1DM associated with IgA deficiency.
Once a year for 4 years after T1DM diagnosis, and once every 2 years for the following 6 years.
§Once every 6 months.
CD: Celiac disease; EmA: Antiendomysial antibody; T1DM: Type 1 diabetes mellitus; tTGA: Tissue transglutaminase; UNL: Upper normal limit.

Another important issue is to establish when CD serological screening should be performed in T1DM patients. It has been reported that serological screening for CD at the onset of T1DM allows the identification of 1% of CD patients and that this prevalence rises to at least 5% in the following 5 years.[28] Moreover, according to other published data, antibody positivity for CD may appear within 10 years from the initial diagnosis of T1DM and, in the 90% of cases, within the first 2 years from the diagnosis.[18,25,45–48] Therefore, if CD-serological tests are negative at the onset of T1DM, patients should be reassessed for these antibodies annually for the first 4 years and once every 2 years for the following 6 years.[47,49] In terms of cost–benefit ratio, screening for CD in T1DM is advantageous since antibody screening by tTGA, performed once a year or every 2 years for 10 years, is not expensive and allows the continuous identification of new cases of CD who will benefit from a GFD regimen.

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