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 Typ e 1 diabetes mellitus (Type 1 DM), which displays many of the characteristi cs of the disease found in humans. Nicotinamide (NA) is currently being tes ted 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 t he effect of NA administration on Type 1 DM incidence. Methods The effect of NA in the diet was examined, both with and without ca rbohydrate in the form of a sucrose supplement, on diabetes incidence and i nsulitis levels in the NOD mouse. The effects of NA and sucrose were each t ested alone as well as in combination. Results Diabetes was unaltered using a low dose NA-supplemented diet (625 m g/kg diet). Diabetes incidence was also unaltered using unmodified diet tog ether with drinking water supplemented with either 5% or 10% w/v sucrose or plain water for controls. However, with mice given NA-supplemented diet (6 25 mg/kg diet) together with sucrose-supplemented or plain water as previou sly, 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, neit her sucrose nor NA alone altered the incidence of diabetes, but NA treatmen t combined with a 10% w/v sucrose-supplemented drinking water reduced diabe tes incidence (p<0.001). No mice showed alterations in insulitis, blood-glu cose or insulin levels with respect to controls. Conclusion Altering dietary patterns using sucrose can affect the ability o f 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. Copyright (C ) 1999 John Wiley & Sons, Ltd.