Type 1 diabetes and celiac disease: clinical overlap and new insights into disease pathogenesis

Abstract

Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with clinical and pathogenic overlap. The mean prevalence of CD in patients with T1D is about 8 %. Classic intestinal symptoms of CD may not be present in T1D leading to the recommendation for active case finding in this higher risk group. Screening is done with sensitive and specific serologies including tissue transglutaminase (tTG) IgA and deaminated gliadin peptide (DGP) IgA and IgG. Positive serologies are confirmed by the presence of villous atrophy and increased intraepithelial lymphocytes on duodenal biopsy. A strict gluten free diet is recommended, although this can pose challenges for T1D patients who already have dietary restrictions. In aggregate, it appears as if the gluten free diet may help T1D management. T1D and CD have overlapping genetic and environmental risk factors. Among these, non-HLA genetic factors and the gut microbiome are among recent developments that will be discussed in this review.

Figure 1. Genetics, environment and immune dysregulation are primary risk factors identified for both celiac disease (CD) and type 1 diabetes (T1D)

While HLA DQ2 and 8 are well-known risk factors predisposing to both CD and T1D, recently performed genome wide association studies (GWAS) have identified a number of non-HLA genetic factors that are shared by CD and T1D including a number of immune genes. Environmental risk factors shared by CD and T1D include timing of cereal introduction, length of breast-feeding as well as viral infections. Recent work is also elucidating the role of the gut microbiome in both conditions. Finally, immune dysregulation, both innate and adaptive, are central to CD and T1D pathogenesis. While common risk factors predispose to CD and T1D individually, it is not yet known how these risk factors trigger both diseases in a subset of individuals. Therefore, at the present time, screening for CD in T1D and vice versa is advocated in order to identify those manifesting both conditions.