Studies have shown a 4% prevalence of celiac disease in type 1 diabetic patients. Few data, however, are available on the prevalence of type 1 diabetes-related antibodies in patients with celiac disease, with studies being limited by the recruitment of low numbers of children only (1,2). We have assessed prevalence of type 1 diabetes-related autoantibodies (islet cell antibody [ICA], GAD antibody [GADA], and antibodies to the protein tyrosine phosphatase-related IA-2 [anti-IA2]) in a cohort of 378 nondiabetic adults with celiac disease (89 untreated and 289 treated with a gluten-free diet), aged 33.9 ± 14.7 years (range 15.7–81.3), who were cared for at our outpatient clinic. Known duration of gluten withdrawal was <5 years in 146 (48.2%), 5–9 years in 54 (17.8%), and >9 years in 103 (34.0%) patients. GADAs were measured by a radioligand assay using human recombinant GAD 65 as antigen (Medipan Diagnostica, Selchow, Germany), ICAs by indirect immunofluorescence on frozen sections of human blood group 0 pancreas with fluorescein isothiocyanate-conjugated rabbit antibodies, and anti-IA2 by a radioligand assay using highly purified human recombinant IA2 labeled with 125I (Medipan Diagnostica).
Of 289 treated nondiabetic patients, 26 had type 1 diabetes-related autoantibodies, giving a prevalence of 9.0% (95% CI 6.7–12.3). All of them, however, showed no more than one marker positivity (2.8% ICA, 3.1% GADA, 3.1% anti-IA2). Untreated celiac patients had a similar prevalence (10.0%, P = 0.75). In linear regression analysis, levels of anti-IA2 were linearly associated with duration of celiac disease (β = 0.002, P = 0.05). In logistic regression analysis, duration of gluten withdrawal was independently associated with a prevalence of type 1 diabetes-related autoantibodies. With respect to duration <5 years, a fourfold increased risk in patients with duration >9 years was found (95% CI 1.51–10.6), even after adjustment for age, sex, presence of other autoimmune diseases, and compliance to diet. In a mean follow-up time of 3.0 ± 1.3 years (range 1.3–6.5), however, no incident case of type 1 diabetes was diagnosed in either patients with (79.0 person-years) or without (782.7 person-years) autoimmune markers.
In conclusion, this study shows that prevalence of type 1 diabetes-related autoantibodies in adults with celiac disease is high (9.0%), even after dietary gluten withdrawal, and that it increases over time but is associated with low risk of progression to diabetes. These findings are consistent with a role of common genetic susceptibility of both diseases, such as factors involved in intestinal permeability. Case-control studies show association between various dietary factors and risk of type 1 diabetes (3). Dietary gluten could act as modifier rather than determinant of type 1 diabetes, facilitating the progression of other dietary factors to the lamina propria, where they activate the autoimmune response against β-cells.
Address correspondence to Dr. Graziella Bruno, Department of Internal Medicine, Turin University, corso Dogliotti 14, I-10126 Torino, Italy. E-mail: firstname.lastname@example.org.