Response to cyclosporine administration at onset of diabetes in BB rats.

The metabolic and immunological effects of cyclosporine A given at onset of spontaneous Type I diabetes in BB rats were examined, as an analogy to the current use of this agent in newly-diagnosed human diabetics. Diabetes-prone (BBdp) rats were monitored until appearance of hyperglycemia, at which time treatment with both cyclosporine (10 mg/kg/day) and insulin was immediately started. Cyclosporine induced no remission in any rats and did not affect their daily insulin requirements. After 9 weeks of cyclosporine treatment, islet morphology showed the typical "end-stage" picture in all rats, with essentially total beta cell loss. Pancreatic insulin contents were less than 1% of normal levels. During the 9 weeks of cyclosporine treatment, there was a decrease in numbers of peripheral blood Ia-positive lymphocytes, an increase in OX8+ lymphocytes (suppressor/cytotoxic and natural killer cells) but no change in the other subsets. There was a significant increase in plasma creatinine. We conclude that this dose of cyclosporine started at onset of diabetes in BB rats is unable to arrest and/or reverse the beta cell destructive process.