DAPSONE AT ONSET OF DIABETES LOWERS GLYCATED HEMOGLOBIN AND DELAYS DEATH IN NOD MICE

Dapsone (4,4'-diaminodiphenyl sulfone) is a compound that has a large clinical experience due to its antimicrobial effects against mycobacte rium leprae, the causative agent of leprosy, It is increasingly used i n a number of clinical situations where inflammation may play an ancil lary role. An inhibitory effect of the drug or lack thereof in the cum ulative incidence or propagation of diabetes mellitus in the NOD mouse has mechanistic as well as therapeutic implications. We previously sh owed that dapsone administered continuously as a percentage of food to NOD mice inhibits the cumulative incidence of diabetes in a dose depe ndent fashion. In the present experiment, female NOD litter mates were randomized to receive dapsone (0.001% w/w as a percentage of food) at onset of diabetes. There were no differences in weight, blood glucose , or glycated hemoglobin at 10 weeks of age among the animals that wer e ultimately to receive dapsone (n = 10), mouse chow alone (n = 9), or those who did not develop diabetes (n = 3), The mean time to onset of diabetes, mean blood glucose at onset, and mean glycated hemoglobin a t onset did not differ between animals who did or did not receive daps one, Animals receiving dapsone had significantly (p less than or equal to 0.03) lower glycated hemoglobin at weeks 2, 3, and 4 following the onset of diabetes and lived significantly longer following diagnosis of diabetes (7 vs. 4 weeks, p < 0.05). In conclusion, dapsone modulate s the progression of autoimmune diabetes in the NOD mouse even when ad ministered after the initiation of hyperglycemia.