Islet transplantation brings three significant benefits: First it provides tangible benefit now for a small group with severe hypoglycemia usually associated with hypoglycemia unawareness. Second, it is a remarkable clinical research opportunity including providing rarely available pancreatic histopathology. Third, it provides a platform for the introduction of future beta cell replacement technologies.

Return of endogenous insulin production in individuals who have been insulin deficient for many years illustrates the extraordinary ability of the beta cell to sense glucose and other secretagogues and secrete insulin to achieve physiological blood glucose control. Hypoglycemia is prevented by islet transplantation even when exogenous insulin is still administered.

The pancreas of organ donors with type 1 diabetes shows patchy and asynchronous immunopathology that causes beta cell loss. Islets with a normal complement of beta cells co-exist with pseudoatrophic islets without beta cells and stages in-between even several years after diagnosis. Many other insights have come from study of such pancreases through the nPOD program, an international effort that has focused on issues such as the presence of viruses in the pancreas, the persistence of beta cells after diagnosis and abnormalities in autoantibody positive donors.

Islet transplantation remains a technology in evolution with many shortcomings including the short supply of suitable donors, the need for immunosuppression, the gradual loss of islet function and the inability to easily monitor graft function. Future improvements will include the availability of other insulin producing cells such as those derived from embryonic stem cells or from animals. It is expected that all insulin-producing tissue will stimulate the autoimmune response against the beta cell that originally caused the disease. Immune memory specific for the beta cell persists indefinitely after the diagnosis of type 1 diabetes and current immunosuppression and immune tolerance strategies require further development to counter this response.