Early nicotinamide treatment in the NOD mouse: effects on diabetes and insulitis suppression and autoantibody levels.

Nicotinamide, a vitamin B group substance, has previously been shown to prevent diabetes and suppress insulitis in the NOD mouse. In order to further understand its mode of action, we have administered the vitamin orally to female NOD mice from weaning and have examined its effect cross-sectionally (days 40, 106 and 250) on the severity of insulitis, changes in T cell subpopulations, levels of islet cell antibodies (ICA) and insulin autoantibodies (IAA) and diabetes development. At day 40, the incidence and severity of insulitis were much lower in the nicotinamide group (n = 22) than in the control mice (n = 21; 23.8% versus 57.1%, 2.9 +/- 1.4% versus 9.6 +/- 2.6%, respectively). At day 106, the incidence of insulitis increased to 82% in the nicotinamide group (n = 11) and remained similar at day 250 (n = 14). At these two age groups all control mice developed insulitis. The insulitis score increased to about 20% at day 106 in the nicotinamide mice and remained the same at day 250. In the control animals, this score increased from 9.6 +/- 2.6% at day 40 to about 33% and 60% at days 106 and 250, respectively. Diabetes was not detected in the 14 animals maintained on nicotinamide while 4/14 control mice developed the disease with severe insulitis. Most of the immune cells infiltrating the islets were T cells, with higher numbers of L3T4 than Lyt2 cells. At days 40 and 106, the L3T4:Lyt2 cell ratios remained unchanged in both the nicotinamide and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)