Long-term prophylactic insulin treatment can prevent spontaneous diabetes and thyroiditis development in the diabetes-prone bio-breeding rat, while short-term treatment is ineffective

Department of Cell Biology, Immunology Section, University of Groningen, The Netherlands.

OBJECTIVE: Prophylactic insulin treatment has been demonstrated to reduce diabetes development in the diabetes-prone bio-breeding (DP-BB) rat. These prophylactic insulin treatments were given from 50 to 150 days of age. However, several data indicate that the diabetogenic process in DP-BB rats starts well before day 50. DESIGN AND METHODS: DP-BB rats were given bovine insulin pellets from 21 to 60 days of age, from 21 to 100 days of age and from 60 to 100 days of age. At 160 days of age a glucose tolerance test was performed to establish beta-cell function and pancreata collected for histological analysis. RESULTS: Prophylactic insulin treatment from 21 to 100 days of age gave a 42% reduction of diabetes incidence. The other treatment protocols had no effect. Non-diabetic rats treated with insulin from day 21 to 100 showed normal glucose tolerance and no sign of insulitis at 160 days of age. Non-diabetic rats of the control group and the other treatment groups showed normal glucose tolerance, but a slight increase of insulitis. Interestingly, the 21-100 day treated rats showed reduced serum levels of anti-colloid antibodies as compared with the control group. CONCLUSIONS: These results show that short-term prophylactic insulin treatment cannot prevent diabetes and thyroiditis development in DP-BB rats. The prophylactic treatment must start well before 60 days of age and be prolonged into the phase when the rats normally become diabetic to reduce diabetes incidence. These findings imply that in the human situation prophylactic insulin treatment must be prolonged over the normal range of diabetes onset.