Nutritional components and their influence on the pathogenesis of murine autoimmune diabetes in early life

Introduction: Diet can influence the development of autoimmune diabetes. Due to the complexity of diets, it is difficult to determine if associations with diabetes can be attributed to single components. The aim of this study was to develop basal diabetogenic and non-diabetogenic diets that can be used to test the influence of specific dietary components on diabetes incidence in the NOD mouse.

Method: The reference diet used was Altromin 1324 which contains various protein sources (wheat, wheat bran, wheat middling, soy, barley, corn, fish meal, whey, lupin). Three isocaloric isonitrogenic basal diets with a 16% protein content were prepared in which the protein sources were Diet A. casein (66%), soy (15%), wheat (18%); Diet B. casein (66%) and soy (34%); Diet C. poultry (66%) and soy (34%). Diets were otherwise identical. Mice were fed respective diets throughout life (including mothers) or only after weaning.

Results: Mice that received the Altromin diet after weaning had a high diabetes rate (66% by 20 weeks). The diabetes rate was similar in mice that received the basal casein/soy/wheat Diet A (63% by 20 wks) indicating this as a basal diabetogenic diet. Mice receiving wheat-free, casein-containing Diet B had a reduced diabetes rate (33% by 20 wks), and mice that received the casein and wheat-free Diet C had the lowest rate of diabetes (<20% by 20 wks). Diet C was subsequently fed to mothers, whereas after weaning pups received the same casein- and wheat-free diet supplemented with single food components, including gluten. These ongoing experiments show that gluten does not significantly increase the diabetogenicity of the basal diet (23% by 20 wks), but that other supplements do.

Conclusions: Both casein and wheat proteins promote diabetes in the NOD mouse. The use of a basal casein- and wheat-free diet allows investigation into single food components that are diabetogenic in this model. Preliminary data indicate that wheat components other than gluten and proteins derived from sources other than wheat and casein will be diabetogenic.