Type 2 Diabetes Mellitus Phenotype and Graft Survival After Islet Transplantation

Transplantation of allogeneic islets of Langerhans is an option for treating patients with unstable type 1 diabetes mellitus (DM) (1). Infused islets lead to blood glucose stabilization, resulting in better metabolic control, lower incidence of hypoglycemia and improvement in long-term quality of life (2,3,4,5,6). However, not all patients are able to achieve insulin independence after transplant and a gradual decrease in islet function has been observed over time (5). Several factors have been associated with graft dysfunction and failure after islet transplantation (ITx) (6). Among them, recipient's body mass index (BMI) appears to play an important role (7). Body fat accumulation decreases insulin sensitivity, resulting in increased insulin demands (8) which has been associated with metabolic disarrangement in other models of beta-cell loss. In type 2 DM subjects, overweight/obesity is a well-known risk factor for hyperglycemia onset in genetic predisposed individuals (9). Similarly, type 1 DM, which is caused by an association of human leukocyte antigen (HLA) susceptibility genes and ambient triggers can initiate earlier if excessive weight is gain during childhood (10). Recently, clinical features of type 2 DM were recognized in adults with type 1 DM and the mixed phenotype, known as “double diabetes”, was associated with increased risk for chronic complications (11). So far, the effects of a mixed DM phenotype on islet graft function in ITx recipients have not been studied. The aim of this study was to determine if risk factors for type 2 DM, particularly genetic predisposition and increased BMI, could affect islet graft function in type 1 DM ITx recipients.