A COMBINED CASEIN-FREE-NICOTINAMIDE DIET PREVENTS DIABETES IN THE NODMOUSE WITH MINIMUM INSULITIS

We have previously shown that diabetes in the NOD mouse can be prevent ed if mice are placed from weaning on an infant formula diet in which the protein source is replaced with casein hydrolysate (Pregestimil) o r soy protein (Prosobee), or if 1% nicotinamide is given in the drinki ng water. Nicotinamide somewhat suppresses insulitis but the hydrolyse d casein formula does not. In this study, Prosobee was given concurren tly with oral nicotinamide from weaning and their effects on the devel opment of insulitis and diabetes measured. These effects were also ass essed in mice given Prosobee alone from conception (day -20) or from w eaning. Unlike the earlier experiments, a marked suppression of insuli tis was observed when the diets and nicotinamide were given concurrent ly (mean insulitis scores +95% confidence intervals (back transformed) : day 40 = 0.4% [0.03, 1.17] vs. 12.5% [2.52, 28.40] and at day 90 = 8 .8% [3.65, 15.68] vs. 48.1% [33.89, 62.49], P = 0.0001). A similar sup pression was observed on day 90 with Pregestimil combined with nicotin amide 7.3% [3.88, 11.70] vs. 43.8% [32.59, 55.35] (P = 0.0001). Qualit atively, introduction of Prosobee from conception appeared to elicit a greater degree of suppression of insulitis than when introduced from day 21. Insulitis lesions were examined immunohistochemically for CD4, CD8 and MAC-1 cells. The proportion of these cells was not different for any regime despite the great differences in total number of inflam matory cells in and around the islets of mice fed the combined diet. A ll the three dietary treatments (Prosobee from day -20, Prosobee from day 21, Prosobee + nicotinamide from day 21) resulted in substantial p rotection from diabetes in mice followed until 250 days. We conclude t hat the complete prevention of diabetes in the NOD mouse fed a casein- free diet together with nicotinamide is accompanied by marked inhibiti on of insulitis, which is not seen when either dietary agent is introd uced alone. The somewhat greater suppression of insulitis in mice give n the soy diet from conception compared to those fed from day 21 may i ndicate that even maternal diet during gestation may influence diabete s outcome in the offspring.