The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program

The UK islet allotransplant program is nationally funded to deliver 1 or 2 transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus 2 transplants; time between 2 transplants and graft survival (stimulated C-peptide >50pmol/L) and function. 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23(68%) single and 47(94%)(p=0.002) two transplant recipients (separated by (median(IQR))6(3-8) months). 64% recipients of 1 or 2 transplants with uninterrupted function at 12 months sustained graft function at 6-years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p<0.01). Despite 1.9-fold greater transplanted mass in recipients of 2 versus 1 islet infusion (12,218(9,291-15,417) vs 6,442(5,156-7,639) IEQ/kg;p<0.0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta -0.35; p=0.02). Graft survival over the first 12 months was greater in recipients of 2 versus 1 islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.