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

Abstract and Introduction

Abstract

Celiac disease (CD) is one of the most frequent autoimmune disorders occurring in Type 1 diabetes mellitus (T1DM). The prevalence of CD in T1DM varies from 3 to 16%, with a mean prevalence of 8%. The clinical presentation of CD in T1DM is classified as symptomless in approximately half of cases, but a more accurate analysis often discloses a wide array of symptoms suggestive of CD. Both T1DM and CD show the same genetic background and an abnormal small intestinal immune response with inflammation and a variable grade of enteropathy. Serological screening for CD should be performed in all T1DM patients by means of antibodies to tissue transglutaminase at T1DM onset. T1DM patients found to be celiacs must be treated by a gluten-free diet. Potential CD cases (especially when asymptomatic) should be kept on a gluten-containing diet with a careful clinical and antibody follow-up, since many of them will not develop villous atrophy.

Introduction

Type 1 diabetes mellitus (T1DM) is an immune mediated disease, characterized by loss of the insulin-producing β cells of the islets of Langerhans in the pancreas, leading to insulin deficiency.[1] The incidence of T1DM, especially in childhood, has rapidly grown during the 20th Century and at the beginning of the third millennium, its prevalence in the general population has been evaluated to be approximately 2–3%.[2,3] Owing to a common genetic background and interplay between environmental and immunological factors, patients with T1DM are at high risk of developing other autoimmune disorders. A total of 15–30% of patients with T1DM display Hashimoto's thyroiditis,[4–6] whereas a small percentage (0.5%) develop Addison's disease.[6] The most frequent autoimmune disorder diagnosed in T1DM patients after autoimmune thyroiditis is celiac disease (CD).[7]

Celiac disease is an immune-mediated disorder triggered by gluten exposure in genetically predisposed individuals, causing small bowel mucosa atrophy with a more or less evident malabsorption syndrome.[8] The fact that CD prevalence is higher in T1DM patients than in the general population is long-established a well-defined fact. This close association has been ascribed to the same HLA pattern, namely HLA-DQ2 and/or DQ8, which predisposes individuals to both disorders. The risk of developing CD in T1DM patients is partially increased by the presence of HLA-DQB102-DQA105 and the presence of a variant of another MHC gene, TNF-α-308A.[9] Moreover, it has been hypothesized that MYO9B (myosin IXB) polymorphisms might be involved in the development of both T1DM and CD, presumably through an alteration of the intestinal permeability.[10]

Gluten consumption might be a shared causative factor for both diseases, as confirmed by the possible concomitant onset of both disorders.[2] Moreover, withdrawal of gluten in patients with CD diagnosis without T1DM, is rarely associated with the appearance of immune markers of T1DM and the development of T1DM.[11] The detection of antibodies against tissue transglutaminase (tTGA) in the experimental model of non-obese diabetic (NOD) mice further strengthens the close linkage between these two autoimmune disorders.[12]

Well-established viral infections, particularly those caused by enteroviruses, can play a role in triggering T1DM.[13] Undiagnosed CD, which causes an alteration of the intestinal barrier permeability to large protein molecules and probably also enteric viruses, especially coxsackievirus B, could favor the onset of T1DM. The hypothesis that viral infections would have a role in the pathogenesis of both disorders has been strengthened by the demonstration that rotavirus, responsible for gastrointestinal infections in infancy, has been recently recognized as one of the pathogenic factors of CD.[14]

By reviewing data from the literature, we aim to shed light on clinical and immunological features of CD occurring in patients with T1DM.

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