Objective: The long-term safety and efficacy of pancreatic islet transplantation are still unclear because of the limited data comparing it to intensive insulin treatment (IIT). In Japan, pancreases for islet transplantation have been obtained from donors after cardiac death (DCD), unlike in Western countries where donation is made following brain death (DBD). We compared patients who underwent islet transplantation using DCD to patients who received IIT after a mean follow-up of 10 years.
Methods: Nine type 1 diabetic patients with severe hypoglycaemia unawareness were enrolled. Ten islet transplantations were performed in five type 1 diabetic patients (Tx group) followed by immunosuppressive therapy with basiliximab, sirolimus and tacrolimus. All donors were DCD at the time of harvest. Four patients (IIT group) registered in the recipient list of islet transplantation were receiving IIT. In the Tx group, the duration of sustained islet graft function, insulin requirements, HbA1c and eGFR were assessed 10 years after the first islet transplant. The records of adverse effects were limited to malignancies and serious adverse events. Glycaemic control, severe hypoglycaemia, insulin requirements and the onset of diabetic complications were analysed in both groups.
Results: In the Tx group, overall graft survival was 20% at 10 years. Insulin requirements decreased (pretransplant, 30 ± 9.5 U/day; 10 years after transplant, 24 ± 17 U/day) and HbA1c levels improved (pretransplant, 8.8 ± 2.5%; 10 years after transplant, 7.9 ± 2.1%). All patients experienced a progressive decline in the level of C-peptide. The eGFR levels slightly decreased (pretransplant, 80.8 ± 13.3 ml/min/1.73 m²; 10 years after transplant, 61.2 ± 7.9 ml/min/1.73 m²), but no patients developed renal failure. Severe hypoglycaemia unawareness was resolved in all recipients; however, at least one patient had recurrent severe hypoglycaemia after the loss of graft function. No patients experienced opportunistic infections or lymphoma; however, one patient developed early-stage gastric cancer. In the IIT group, both insulin requirements and HbA1c levels remained constant (preregistration, 48.8 ± 10.8 U/day; 10 years after registration, 45.3 ± 7.6 U/day and preregistration, 7.7 ± 0.8%; 10 years after registration, 7.7 ± 0.8%, respectively). The eGFR levels were stable (preregistration, 86.3 ± 12.5 ml/min/1.73 m²; 10 years after registration, 74.8 ± 10.0 ml/min/1.73 m²), and no patients developed renal failure. All patients had severe hypoglycaemia unawareness. In both groups, no progression of diabetic complications, such as retinopathy or neuropathy, was observed during the10-year study period.
Conclusion: Islet transplantation employing DCD can reduce insulin requirements and improve HbA1c levels without severe hypoglycaemia unawareness and ensures long-term safety. Further improvements in the islet transplantation protocol are necessary to accomplish better clinical outcomes than IIT.