Long-Term Insulin-Independence After Allogeneic Islet Transplantation for Type 1 Diabetes: Over the 10-Year Mark

Abstract

Results of islet of Langerhans transplantation have markedly improved in recent years, but most patients still lose insulin independence in the long-term.We report herein the longest (over 11 years) case of insulin independence after allogeneic islet transplantation. The subject had a 27-year history of type 1 diabetes and received a single islet-after-kidney graft of 8800 islet equivalents (IEQ)/kg, pooled from 2 donors. Insulin was discontinued by 3 months posttransplant and the patient has remained off insulin ever since. Yearly follow-up studies have revealed normal metabolic control, including normal oral glucose tolerance test (OGTT). Reasons for success may involve choice of immunosuppression, low metabolic demand and low immune responsiveness as suggested by an excellent HLA matching and a high count of circulating regulatory T cells. This observation is so far an exceptional case, but clearly demonstrates the validity of the concept that long-term insulin independence after allogeneic islet transplantation is an achievable target. With this picture of the current status of islet transplantation, the analysis of cases of long-term insulin independence could be critical for the understanding of the determinants of long-term failure or success. We report herein the first case of islet allogeneic transplantation in a patient

Impact of Islet Transplantation on Diabetes Complications and Quality of Life

“…1) [47••]. Notably, Davalli et al [48] and Berney et al [49] described two cases of long-term (>4 years and >11 years, respectively) successful intrahepatic islet transplantation into T1D patients chronically immunosuppressed for a prior kidney graft.…”

Update on Islet Transplantation

“…In addition, the achievement of longer-term insulin independence is highly sought. Although independence out to 10 yr is possible (Berney et al 2009) this is certainly not standard. The focus of this work is to review the advances in islet transplantation that have made the current results possible and to look ahead at some of the future advances aimed at achieving these goals.…”

Autoimmune diabetic patients undergoing allogeneic islet transplantation: are we ready for a regulatory T-cell therapy?

“…Interestingly, it was reported that one exceptional T1D patient who remained insulin-free 11 years after islet transplantation had a significantly higher frequency of circulating nTregs, as compared to healthy age matched controls [71]. Similarly, IL-10 production by total PBMC isolated from islet transplanted patients who were insulin-independent was significantly higher, as compared to that produced by transplanted and insulin-dependent subjects [62].…”