Does islet size really influence graft function following clinical islet transplantation?

Background It has been proposed that islet transplants comprised primarily of small rather than large islets may provide better graft function, due to their lower susceptibility to hypoxic damage. Our aim was to determine whether islet size correlated with in vivo graft function in islet transplant recipients with C peptide negative type 1 diabetes when islets have undergone pre-transplant islet culture. Methods Human pancreatic islets were isolated, cultured for 24hours and infused by standardised protocols. 90 min-stimulated C-peptide concentrations were determined during a standard meal tolerance test 3 months post-transplant. The islet isolation index (IEq/islet number) was determined immediately after isolation and again before transplantation (after tissue culture). This was correlated with patient insulin requirement or stimulated C-peptide. Results Changes in insulin requirement did not significantly correlate with islet isolation index. Stimulated C-peptide correlated weakly with IEq at isolation (p=0.40) and significantly with IEq at transplantation (p=0.018). Stimulated C-peptide correlated with islet number at isolation (p=0.013) and more strongly with the islet number at transplantation (p=0.001). In contrast, the correlation of stimulated C-peptide and islet isolation index was weaker (p=0.018) and this was poorer at transplantation (p=0.034). Using linear regression, the strongest association with graft function was islet number (r=0.722, p=0.001). Islet size was not related to graft function after adjusting for islet volume or number. Conclusion These data show no clear correlation between islet isolation index and graft function; both small and large islets are suitable for transplantation provided the islets have survived a short culture period post-isolation.