Long-Term Protection from Severe Hypoglycemia Following Pancreas Transplantation: A Single-Center Cohort Study

Background: Patients with type 1 diabetes complicated by severe hypoglycemia and impaired awareness remain at high risk of mortality despite advances in diabetes treatment. Pancreas transplantation offers definitive β-cell replacement; however, contemporary real-world data on hypoglycemia outcomes are limited. Methods: We performed a retrospective single-center cohort study of adult patients undergoing pancreas transplantation at The Mount Sinai Hospital between 1 January 2010 and 31 December 2024. Transplant types included simultaneous pancreas–kidney (SPK), pancreas after kidney (PAK), and pancreas transplant alone (PTA). The primary outcome was the incidence of severe hypoglycemia following transplantation, with secondary outcomes including graft survival, patient survival, biopsy-proven rejection, and infectious complications. Post-transplant HbA1c and continuous glucose monitoring data were not systematically captured and could not be analyzed. Results: A total of 100 pancreas transplants were performed (SPK 73%, PAK 26%, PTA 1%), over a median follow-up of 8.5 years (IQR 4.5–13.7). Pretransplant hypoglycemia or hypoglycemia unawareness was present in 63% of recipients. Documented impaired awareness specifically was recorded in a smaller subset (9%). No episodes of severe hypoglycemia occurred following transplantation, and hypoglycemia unawareness resolved in all patients with available follow-up. Two patients (2%) had a hypoglycemic episode recorded post-transplant; in one, the episode occurred after graft failure while on insulin, and neither was a severe (third-party-assisted) event in a functioning graft. Death-censored graft survival was 94.0% at 1 year, 91.6% at 3 years, 83.0% at 5 years, and 80.5% at 10 years, while patient survival was 95.0%, 89.5%, 88.2%, and 84.2% at the same time points. Rejection occurred in 21%, and infectious complications in 31% of recipients. Conclusions: Pancreas transplantation provided complete and durable protection from clinically documented severe hypoglycemia, with excellent long-term graft and patient survival. In the absence of systematic post-transplant HbA1c and continuous glucose monitoring data, these findings should be read as freedom from clinically recognized severe hypoglycemic events rather than as documented normoglycemia, supporting its role as the most definitive β-cell replacement strategy in appropriately selected patients.