Islet Autotransplant Outcomes After Total Pancreatectomy: A Contrast to Islet Allograft Outcomes

TLDR

Islet allografts initially achieve high insulin independence, but rates drop sharply after one year, likely due to donor brain death, prolonged cold ischemia, immunosuppression, and immune responses. This study compares islet autotransplantation (IAT) outcomes to allografts, aiming to demonstrate IAT’s durable function despite lower beta‑cell mass. IAT function was classified as full, partial, or failed based on insulin use and C‑peptide positivity, and Kaplan‑Meier analysis linked function and insulin independence to islet yield in 173 patients. IATs showed 32% insulin independence at one year, with 85% of initially functioning grafts and 74% of insulin‑independent patients remaining so at two years, and 47% insulin independence at five years—outperforming allografts whose two‑year insulin‑independence rate was 45%.

Abstract

Islet allografts are currently associated with a high rate of early insulin independence, but after 1 year insulin-independence rates rapidly decline for unclear reasons. In contrast, as shown here, islet autotransplants (IATs) show durable function and extended insulin-independence rates, despite a lower beta-cell mass.IAT function was determined in 173 patients after total pancreatectomy at our center. Islet function was considered full in insulin-independent patients, partial when euglycemic on once-daily long-acting insulin (all tested were C-peptide positive), and failed if on a standard diabetic regimen. Outcomes for autoislet recipients by Kaplan-Meier survival analysis were compared with those of alloislet recipients in the Collaborative Islet Transplant Registry.IAT function (full/partial combined) and insulin independence correlated with islet yield. Overall only 65% functioned within the first year, and only 32% were insulin independent, but of IATs that functioned initially (n=112), 85% remained so 2-years later, in contrast to 66% of allografts (n=262). Of IAT recipients who became insulin independent (n=55), 74% remained so 2-years later versus 45% of initially insulin-independent allograft recipients (n=154). Of IATs that functioned or induced insulin independence, the rates at 5 years were 69% and 47%, respectively.Islet function is more resilient in autografts than allografts. Indeed, the 5-year insulin-independence persistence rate for IATs is similar to the 2-year rate for allografts. Several factors unique to allocases are likely responsible for the differences, including donor brain death, longer cold ischemia time, diabetogenic immunosuppression, and auto- and alloimmunity. IAT outcomes provide a minimum theoretical standard to work toward in allotransplantation.