GLIMEPIRIDE-INDUCED PREVENTION OF DIABETES AND AUTOIMMUNE EVENTS IN THE BB RAT - REVISED

The purpose of this study was to determine whether Glimepiride, an ora l sulfonylurea drug, prevents the onset of diabetes in diabetic prone BB rats. S750181, a sulfonylurea drug that has minimal in vivo glucose metabolic effects, was also tested. In addition, the shortest period of sulfonylurea treatment required for prevention was determined. Eigh ty rats were studied for all treatment periods with 40 receiving a dai ly oral gavage dosage of Glimepiride and 40 receiving a daily oral gav age dosage of vehicle solution. Diabetes onset was monitored by glycos uria and blood glucose levels. In study I, with a treatment period of 35-142 days of age, Glimepiride-treated rats showed a 32% incidence of diabetes, whereas control rats had a diabetes incidence of 55% (p<0.0 4). In study II, with a treatment period of 60-140 days of age, Glimep iride-treated rats showed a 29% incidence of diabetes compared to 54% in controls (p<0.03). Further, comparing the time of diabetes onset be tween the Glimepiride and control groups showed that Glimepiride delay s diabetes onset (p<0.02). In study III, with a treatment period of 50 -100 days of age, Glimepiride-treated rats showed a 17% overall diabet es incidence at 170 days, whereas the controls were 43% (p<0.01). In s tudy IV, with a treatment period of 60-140 days of age, S750181-treate d rats showed a 38% diabetes incidence and the control group showed a 43% diabetes incidence. There was no significant delaying or preventio n effect observed in the S750181 group. To determine if Glimepiride af fected autoimmune events, the severity of islet inflammation was exami ned. In study I, islet histology from total and nondiabetic animals in dicated that Glimepiride-treated rats had a lower severity of islet in flammation than that of the control rats (p=0.023). These studies show that a) Glimepiride has diabetes preventive effects, b) shorter treat ment periods of only 40 days can be effective and c) Glimepiride decre ases the severity of islet inflammation.