Diet can influence the ability of nicotinamide to prevent diabetes in the non-obese diabetic mouse: a preliminary study.

BACKGROUND

The non-obese diabetic (NOD) mouse is a widely used model of Type 1 diabetes mellitus (Type 1 DM), which displays many of the characteristics of the disease found in humans. Nicotinamide (NA) is currently being tested in large-scale, multi-centre human trials for the prevention of Type 1 DM in subjects considered 'at risk' of developing the disease. Human trial populations will certainly differ in their dietary patterns and alterations were made to the diet given to NOD mice to determine if this could alter the effect of NA administration on Type 1 DM incidence.

METHODS

The effect of NA in the diet was examined, both with and without carbohydrate in the form of a sucrose supplement, on diabetes incidence and insulitis levels in the NOD mouse. The effects of NA and sucrose were each tested alone as well as in combination.

RESULTS

Diabetes was unaltered using a low dose NA-supplemented diet (625 mg/kg diet). Diabetes incidence was also unaltered using unmodified diet together with drinking water supplemented with either 5% or 10% w/v sucrose or plain water for controls. However, with mice given NA-supplemented diet (625 mg/kg diet) together with sucrose-supplemented or plain water as previously, diabetes was reduced in the NA+10% sucrose group (p<0.001). Finally, a higher dose of NA was given in supplemented diet (1000 mg/kg). Again, neither sucrose nor NA alone altered the incidence of diabetes, but NA treatment combined with a 10% w/v sucrose-supplemented drinking water reduced diabetes incidence (p<0.001). No mice showed alterations in insulitis, blood-glucose or insulin levels with respect to controls.

CONCLUSIONS

Altering dietary patterns using sucrose can affect the ability of NA to prevent diabetes in the NOD mouse. This finding may be relevant for human studies with NA aimed at preventing Type 1 DM and suggests that diet may need to be monitored or even controlled in these studies.