Patients in whom
type 1 diabetes is complicated by impaired awareness of
hypoglycemia and recurrent episodes of severe
hypoglycemia are candidates for islet or
pancreas transplantation if severe
hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in period that provides access to
hypoglycemia-specific education including behavioral
therapies,
insulin analogs, and diabetes technologies under the close supervision of a specialist
hypoglycemia service. Patients with
type 1 diabetes and
end-stage renal failure who cannot meet clinically appropriate glycemic goals or continue to experience severe
hypoglycemia after completion of a formalized medical optimization program under the guidance of an expert diabetes care team are candidates for islet or
pancreas transplantation either simultaneously with or after a previous kidney transplant. Similarly, patients with
type 2 diabetes and problematic
hypoglycemia or
renal failure who meet these criteria are considered candidates for islet replacement. Likewise, patients with
pancreatectomy-induced diabetes in whom an islet autograft was not available or deemed inappropriate are candidates for islet or
pancreas transplantation if extreme glycemic lability persists despite best medical
therapy. To justify participation of these transplant candidates in early-phase trials of porcine islet cell products, lack of timely access to islet or pancreas allotransplantation due to allosensitization, high islet dose requirements, or other factors, or alternatively, a more favorable benefit-risk determination associated with the xenoislet than the alloislet or allopancreas transplant must be demonstrated. Additionally, in non-uremic xenoislet recipients, the risks associated with diabetes must be perceived to be more serious than the risks associated with the xenoislet product and the rejection prophylaxis, and in xenoislet recipients with
renal failure, the xenoislet product and immunosuppression must not impact negatively on renal transplant outcomes. The most appropriate patient group for islet
xenotransplantation trials will be defined by the specific characteristics of each investigational xenoislet product and related technologies applied for preventing rejection. Selecting recipients who are more likely to experience prolonged benefits associated with the islet xenograft will help these patients comply with lifelong monitoring and other public health measures.