Results of the Australian Multi-Centre Trial of Clinical Islet Transplantation (#67)
Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The Australian Islet Transplant Consortium has just completed a multi-centre study was to evaluate the effectiveness of clinical islet allotransplantation to alleviate severe hypoglycaemia unawareness in patients with Type 1 diabetes. Patients received 1 to 3 islet infusions and an immunosuppressive protocol of ATG induction followed by tacrolimus and mycophenolate mofetil (MMF) maintenance immunosuppression which was to switched to sirolimus and MMF at 6 months. Islets were cultured for 24 hours prior to transplantation. The primary outcome was achieved with an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 4 remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2nmol/l had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. Islet transplantation is a viable alternative in adult patients with long-standing type 1 diabetes and poor diabetic control due to severe hypoglycmemia unawareness. Improvements in islet yield and less toxic immunosuppression would improve outcomes and increase the demand for the procedure. Nevertheless in its current form islet transplantation provides better control of hypoglycemia and better HbA1c than intensive insulin therapy using insulin pumps in this group of patients.