Gluten-free but also gluten-enriched (gluten+) diet prevent diabetes in NOD mice; the gluten enigma in type 1 diabetes

Diabetes Metab Res Rev. Jan-Feb 2008;24(1):59-63. doi: 10.1002/dmrr.748.

Abstract

Background: Environmental factors such as nutrition or exposure to infections play a substantial role in the pathogenesis of type 1 diabetes (T1D). We have previously shown that gluten-free, non-purified diet largely prevented diabetes in non-obese diabetic (NOD) mice. In this study we tested hypothesis that early introduction of gluten-enriched (gluten+) diet may increase diabetes incidence in NOD mice.

Methods: Standard, gluten-free, gluten+ modified Altromin diets and hydrolysed-casein-based Pregestimil diet were fed to NOD females and diabetes incidence was followed for 310 days. Insulitis score and numbers of gut mucosal lymphocytes were determined in non-diabetic animals.

Results: A significantly lower diabetes incidence (p < 0.0001) was observed in NOD mice fed gluten-free diet (5.9%, n = 34) and Pregestimil diet (10%, n = 30) compared to mice on the standard Altromin diet (60.6%, n = 33). Surprisingly, gluten+ diet also prevented diabetes incidence, even at the level found with the gluten-free diet (p < 0.0001, 5.9%, n = 34). The minority of mice, which developed diabetes on all the three diabetes-protective (gluten+, gluten-free, Pregestimil) diets, did that slightly later compared to those on the standard diet. Lower insulitis score compared to control mice was found in non-diabetic NOD mice on the gluten-free, and to a lesser extent also gluten+ and Pregestimil diets. No substantial differences in the number of CD3(+), TCR-gammadelta(+), and IgA(+) cells in the small intestine were documented.

Conclusions: Gluten+ diet prevents diabetes in NOD mice at the level found with the non-purified gluten-free diet. Possible mechanisms of the enigmatic, dual effect of dietary gluten on the development of T1D are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / analysis
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Diet*
  • Female
  • Genetic Predisposition to Disease
  • Glutens / administration & dosage*
  • Ileum / immunology
  • Immunoglobulin A / metabolism
  • Immunoglobulin M / metabolism
  • Islets of Langerhans / pathology
  • Jejunum / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Receptors, Antigen, T-Cell, gamma-delta / analysis

Substances

  • CD3 Complex
  • Immunoglobulin A
  • Immunoglobulin M
  • Receptors, Antigen, T-Cell, gamma-delta
  • Glutens