Shapiro AMJ et al. (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355: 1318–1330

In diabetic patients whose condition is refractory to conventional insulin treatment, a possible therapeutic approach is the transplantation of islets obtained from the pancreata of deceased donors. From nine centers, Shapiro and colleagues report results achieved by islet transplantation combined with glucocorticoid-free immunosuppressive therapy, which is known as the Edmonton protocol.

A total of 77 ABO-compatible islet transplantations were performed on 36 patients with treatment-refractory type 1 diabetes mellitus. Identical procedures were used. By 1 year after the final transplantation, insulin-independence with adequate glycemic control was observed in 16 patients, partial graft function in 10 patients, and complete graft loss in 10 patients. In total, 21 patients attained insulin-independence during the trial. By the end of the second post-transplant year, however, insulin-independence persisted in only 5 patients. Attainment of insulin independence was considerably more likely in patients with no detectable antibodies against islet antigens, but loss of insulin-independence was unrelated to such antibody levels. Previous experience with islet transplantation clearly affected the outcome of the procedure. The main adverse effects of the procedure were immunosuppression-related complications (e.g. mouth ulceration, anemia and leucopenia) and declines in renal function.

These findings imply that although insulin production can be transiently restored by the Edmonton protocol, whole-pancreas transplantation is more likely to result in long-term insulin-independence. Advances in islet transplantation await improved techniques for isolating islets and the development of immunosuppressive agents with reduced toxicity. In view of the limited availability of donors, there is a great need for other sources of insulin-producing cells that can be used for islet transplantation.