Introduction: Islet transplantation is an effective treatment option for patients with type 1 diabetes (T1D) suffering from severe hypoglycemia. While high-quality prospective clinical trials have demonstrated its efficacy, reports on clinical outcomes in Asia, particularly Japan, remain scarce. Considering the noted variations in islet function between Japanese and Western patients in genetic analysis studies, validating islet transplantation outcomes in Japanese patients is imperative. To confirm the efficacy and safety of the procedure, a clinical trial of islet transplantation was conducted in Japan, and the results were published.
Methods: This multicenter, single-arm study aimed to assess the clinical efficacy and safety of immunosuppressive therapy for islet transplantation. The immunosuppressive regimen included antithymocyte globulin, etanercept, a calcineurin inhibitor, and mycophenolate mofetil. Two groups were defined based on tacrolimus target trough levels: Group 1 targeted 3–6 ng/mL 3 months after transplantation, while Group 2 targeted 10–12 ng/mL. The primary endpoint was achieving an HbA1c level <7.4% on day 365 without experiencing severe hypoglycemic events (SHEs) from 1 month to 1 year post-transplantation.
Results: The study included eight recipients with a median IQR age of 48.0 (43.2–56.0) years at the time of their first islet transplant. The median IQR age of donors in cases that resulted in transplantation was 43 (39–46) years, with 3 donors following cardiac death and 13 following brain death. The primary endpoint was achieved 6 recipients (75%) and 4 subjects (57.1%) also achieved the primary endpoint criteria evaluated at day 730. Median HbA1c levels decreased from 7.3% at baseline to 6.3% on day 365 and 6.1% on day 730 (P = 0.02). Insulin independence was achieved by 0% of subjects on day 365 and 28.6% on day 730. Graft survival rates were 87.5% and 75% on days 365 and 730, respectively. A comparison between Group 1 and 2 revealed that all subjects in Group 2 maintained functional grafts until day 730, while in Group 1, graft survival rates were 66% on day 365 and 33% on day 730 (P = 0.004). No complications from intraportal transplantation, such as intraperitoneal hemorrhage or portal vein embolism, were observed. Additionally, there were no infectious complications among the recipients.
Conclusion: Islet transplantation improves glycemic control and protects against SHEs in Japanese patients with T1D. Future research is needed to determine optimal calcineurin inhibitor trough levels and confirm the possibility of long-term graft survival.