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Aims/hypothesis: Islet transplantation has been studied in small cohorts of recipients with type 1 diabetes complicated by severe hypoglycaemic events (SHEs). We determined factors associated with favourable outcomes in a large cohort of recipients reported to the Collaborative Islet Transplant Registry (CITR). Methods: In 398 non-uraemic islet transplant alone (ITA) recipients with type 1 diabetes and SHEs, transplanted between 1999 and 2015 and with at least 1 year follow-up, we analysed specified favourable outcomes against each of all available characteristics of pancreas donors, islet grafts, recipients and immunosuppressive regimens, as well as immunosuppression and procedure-related serious adverse events (SAEs). Results: Four factors were associated with the highest rates of favourable outcomes: recipient age ≥35 years; total infused islets ≥325,000 islet equivalents; induction immunosuppression with T cell depletion and/or TNF-α inhibition; and maintenance with both mechanistic target of rapamycin (mTOR) and calcineurin inhibitors. At 5 years after the last islet infusion, of the recipients meeting these four common favourable factors (4CFF; N=126), 95% were free of SHEs, 76% had HbA1c <53 mmol/mol (7.0%), 73% had HbA1c <53 mmol/mol (7.0%) and absence of SHEs, and 53% were insulin independent, significantly higher rates than in the remaining recipients (<4CFF; N=272). The incidence of procedural and immunosuppression-related SAEs per recipient that resulted in sequelae, disability or death was low in both the 4CFF (0.056 per person) and <4CFF (0.074 per person) groups. Conclusions/interpretation: In recipients with type 1 diabetes complicated by SHEs, islet transplantation meeting 4CFF protected 95% from SHEs at 5 years after the last islet infusion and exerted a large and significant benefit on glycaemic control, with an acceptable safety profile for this subgroup of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Recently, initiatives have been undertaken to establish an islet transplantation program in Athens, Greece. A major hurdle is the high cost associated with the establishment and maintenance of a clinical-grade islet manufacturing center. A collaboration was established with the University Hospitals of Geneva, Switzerland, to enable remote islet cell manufacturing with an established and validated fully operational team. However, remote islet manufacturing requires shipment of the pancreas from the procurement to the islet manufacturing site (in this case from anywhere in Greece to Geneva) and then shipment of the islets from the manufacturing site to the transplant site (from Geneva to Athens). To address challenges related to cold ischemia time of the pancreas and shipment time of islets, a collaboration was initiated with the University of Arizona, Tucson, USA. An international workshop was held in Athens, December 2011, to mark the start of this collaborative project. Experts in the field presented in three main sessions: (i) islet transplantation: state-of-the-art and the 'network approach'; (ii) technical aspects of clinical islet transplantation and outcomes; and (iii) islet manufacturing - from the donated pancreas to the islet product. This manuscript presents a summary of the workshop. [ABSTRACT FROM AUTHOR]

Clinical islet transplantation has transitioned from curiosity to realistic therapy over the past decade. An estimated 750 patients have undergone intraportal islet-alone transplantation over this period, and a smaller subset received combined islet-kidney transplants. The primary benefit of successful islet transplantation has been to eliminate severe, recurrent hypoglycemia, a problem that has been hard to eliminate by other means in 15% of those with type 1 diabetes. The secondary benefit of independence from insulin has attracted patients, but has had limited sustainability previously, especially with a single-donor graft, but recent results from four independent centers suggest marked improvement in long-term outcome, with 5-year results now approximating solitary pancreas transplantation. Emerging data confirm that islet transplantation can stabilize and reverse several secondary diabetic complications similar to whole pancreas transplantation, but larger, head-to-head trials are needed to compare islet transplantation with best medical therapies. Current goals are to extend durability, and to make islet transplantation more widely available for patients in need. Governmental and health insurance providers in several countries now reimburse islet transplantation as part of clinical care. As the safety of the procedure and of adjunctive immunosuppressive therapies improve, and benefit accrues over potential risk, islet transplantation will be offered earlier in the course of the disease, including newly diagnosed children. The role of islet transplantation in type 2 diabetes has yet to be defined. We review the current status of islet transplantation, and discuss current and future immunosuppressive protocols that will pave the way to more broad application of cellular replacement in diabetes. [ABSTRACT FROM AUTHOR]