Effects of Immunosuppression with Cyclosporine on Beta Cell Function and Clinical Remission in Very Early Overt Type I Diabetes

Abstract

The hypothesis that insulin-dependent diabetes mellitus (IDDM) in man results from destruction of the pancreatic beta cells by an autoimmune process was prompted by circumstantial evidence. The association of IDDM with markers of the major histocompatibility complex suggests that genetic factors are important in determining susceptibility to the disease, and indicates possible involvement of the immune system. Antibody-mediated and cell-mediated immunological phenomena are demonstrable in high-risk subjects in the pre-clinical phase, and in patients with early overt disease. The histology of the Islets of Langerhans was consistent with an inflammatory immune attack. The hypothesis was strengthened by recognition that IDDM can occur in animals as the result of an autoimmune attack on the pancreatic beta cells, and that the process in animals can be prevented by immunomodulatory interventions. On this background, and with growing experience of the use of immunosuppressive drugs in organ transplantation, clinical trials of immunotherapy early in the course of overt IDDM have been undertaken. This summary deals with the now substantial experience with Cyclosporine as the immunosuppressive agent.