Abstract
Gluten proteins differ from other cereal proteins as they are partly resistant to enzymatic processing in the intestine, resulting in a continuous exposure of the proteins to the intestinal immune system. In addition to being a disease-initiating factor in coeliac disease (CD), gluten intake might affect type 1 diabetes development. Studies in animal models of type 1 diabetes have documented that the pathogenesis is influenced by diet. Thus, a gluten-free diet largely prevents diabetes in NOD mice while a cereal-based diet promotes diabetes development. In infants, amount, timing and mode of introduction have been shown to affect the diabetogenic potential of gluten, and some studies now suggest that a gluten-free diet may preserve beta cell function. Other studies have not found this effect. There is evidence that the intestinal immune system plays a primary role in the pathogenesis of type 1 diabetes, as diabetogenic T cells are initially primed in the gut, islet-infiltrating T cells express gut-associated homing receptors, and mesenteric lymphocytes transfer diabetes from NOD mice to NOD/severe combined immunodeficiency (SCID) mice. Thus, gluten may affect diabetes development by influencing proportional changes in immune cell populations or by modifying the cytokine/chemokine pattern towards an inflammatory profile. This supports an important role for gluten intake in the pathogenesis of type 1 diabetes and further studies should be initiated to clarify whether a gluten-free diet could prevent disease in susceptible individuals or be used with newly diagnosed patients to stop disease progression.
Highlights
Gluten proteins differ from other cereal proteins as they are partly resistant to enzymatic processing in the intestine, resulting in a continuous exposure of the proteins to the intestinal immune system
In 1999 we demonstrated that a gluten-free, nonpurified diet largely prevented diabetes onset in NOD mice, as following a gluten-free diet for 320 days reduced the incidence of diabetes from 64% in control mice to 15% in mice on the gluten-free diet [31] with a further incidence reduction to 6% in mice never exposed to gluten either in the uterus or in diet [32]
Beta cell stress can contribute to diabetes development through increased antigen expression, whereas a reduction of diabetes incidence is seen in animal models with early prophylactic insulin treatment of diabetes-prone animals [94]
Summary
Type 1 diabetes incidence has increased over the last two decades, especially in children under the age of 5 [1]. The intestinal CD4+ T cell response is directed against many different epitopes in the gluten proteins. Of particular interest is the observation that most T cell lines from adult CD patients recognise the same 33-mer gliadin peptide. It contains six HLA-DQ2-binding and T cell-stimulatory epitopes and is resistant to intestinal digestion [6]. Several other genes are implicated in susceptibility to both diseases, while up to 15 risk alleles contribute to both diseases [11] This is at least part of the explanation as to why there is a high prevalence of patients with both diseases. Studies have revealed an average CD prevalence of 2– 12% among children with type 1 diabetes [12, 13], and among patients diagnosed with both type 1 diabetes and CD, the majority of the patients were diagnosed with type 1 diabetes before CD, probably due to the diabetes-protective effect of a gluten-free diet [14]
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