Dietary gluten and the development of type 1 diabetes

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.

Rheumatoid arthritis–celiac disease relationship: Joints get that gut feeling

“…tion in animal studies [80][81][82][83][84]. A comparable trend is seen in human 272 diabetes type 1 [85] and CD [86,87] but the effects are controversial in 273 non-celiac gluten sensitivity [88,89]. Most recently, gluten was found 274 to breach tight junction integrity, not only in CD and non-celiac gluten 275 sensitivity, but interestingly enough, also in normal controls [90].…”

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

“…Even though several adverse effects of gliadin have been described, most people can still consume wheat products daily with no symptoms. Both T1D and CD are multifactorial diseases, where genetic predisposition and the mode, timing, and dose of gluten introduction are important for the development [58]. Most people thus tolerate gluten even if several immune stimulating effects have been described in healthy BALB/c and C57BL/6 mice [11,49,59].…”

Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment

“…This is well elucidated for CD, in which negatively charged gliadin peptides as such or modified by tTG bind to DQ2/ DQ8 with high affinity. The lysine position at β71 in DQ2 binds to these residues at positions P4, P6, P7, and position β57 in DQ8 binds at P9 [37,38]. However, these mechanisms have not been fully resolved in T1DM, as the triggering factor is not known in the latter case, but it is anticipated that the "diabetogenic peptide" may be binding to DQ2 and DR3 accompanies it due to linkage disequilibrium.…”