Similar Islet Function in Islet Allotransplant and Autotransplant Recipients, Despite Lower Islet Mass in Autotransplants

Abstract

Despite high initial rates of insulin independence after islet allotransplant for type 1 diabetes, long-term islet function is suboptimal. Possible contributing factors include autoimmune recurrence, alloimmune rejection, or immunosuppressant medication toxicity. In contrast, islet autografts, infused at the time of pancreatectomy for chronic pancreatitis, are not subject to these variables. Islet function was compared in autograft and allograft recipients. Eight autograft and eight allograft recipients, insulin independent or requiring minimal insulin, were matched for similar duration posttransplant (mean 2.1±1.2 years). Eleven healthy control subjects were also enrolled. Subjects underwent oral and intravenous glucose tolerance testing and arginine stimulation testing. Age, gender, body mass index, duration posttransplant, and hemoglobin A1c levels were similar between groups. Glucose tolerance was worse in transplant recipients compared with controls. Alloislet recipients received significantly more islet equivalents per kg body weight (IE/kg) than autograft recipients (9958±6229 IE/kg vs. 4589±1232 IE/kg, P=0.03). However, the glycemic response to oral glucose tolerance testing, the acute insulin response to glucose, and the acute insulin response to arginine did not differ significantly between islet allograft and autograft recipients. Insulin secretion and glucose excursion were similar in allograft and autograft recipients, despite the latter group receiving less than half as many islets. Better preservation of islet mass in the autograft setting is likely related to the lack of autoimmunity, alloimmunity, and immunosuppressive drug toxicity, highlighting the potential for better outcomes in islet allotransplant for type 1 diabetes mellitus with refinements in immunosuppression.