Abstract and Introduction
The goal of this review is to highlight the significant improvements, over the past four decades, in outcomes after a pancreas transplant alone (PTA) in patients with brittle diabetes and recurrent episodes of hypoglycemia and/or hypoglycemic unawareness. A successful PTA—in contrast to intensive insulin regimens and insulin pumps—restores normoglycemia without the risk of hypoglycemia and prevents, halts, or reverses the development or progression of secondary diabetes complications. In this International Pancreas Transplant Registry (IPTR) analysis, we reviewed the records of 1,929 PTA recipients from December 1966 to December 2011. We computed graft survival rates according to the Kaplan-Meier method and used uni- and multivariate analyses. In the most recent era (January 2007–December 2011), patient survival rates were >95% at 1 year posttransplant and >90% at 5 years. Graft survival rates with tacrolimus-based maintenance therapy were 86% at 1 year and 69% at 3 years and with sirolimus, 94 and 84%. Graft survival rates have significantly improved owing to marked decreases in technical and immunologic graft failure rates (P < 0.05). As a result, the need for a subsequent kidney transplant has significantly decreased, over time, to only 6% at 5 years. With patient survival rates of almost 100% and graft survival rates of up to 94% at 1 year, a PTA is now a highly successful long-term option. It should be considered in nonuremic patients with brittle diabetes in order to achieve normoglycemia, to avoid hypoglycemia, and to prevent the development or progression of secondary diabetes complications.
The Diabetes Control and Complications Trial (DCCT) demonstrated, in patients with type 1 diabetes mellitus (T1DM), that intensive insulin therapy may slow the rate of secondary complications of diabetes at the expense of causing (life-threatening) iatrogenic hypoglycemia.[1,2] The definitive treatment for these patients, a successful pancreas transplant, restores normal glucose homeostasis without exposing recipients to the risks of severe hypoglycemia and prevents, halts, or reverses the development or progression of secondary diabetes complications.[3–5]
Pancreas transplants are performed in patients who require insulin administration because of T1DM, T2DM, or total pancreatectomy. Since the first pancreas transplant in December 1966, performed by Drs. William Kelly and Richard Lillehei, the majority (almost 80%) of pancreas transplants have been performed simultaneously with a kidney (SPK) in diabetic and uremic patients.[6,7] An additional 15% of pancreas transplants have been performed after a kidney transplant (PAK) in diabetic and posturemic patients. Only ~8% of all pancreas transplants have been a pancreas transplant alone (PTA), performed in nonuremic patients with brittle (or labile) diabetes (including recurrent episodes of hypoglycemia and/or hypoglycemic unawareness).
The reason that SPK transplants are most common is that SPK recipients are already obligated to immunosuppressive therapy by the kidney graft, so they incur only the added surgical risk of the pancreas transplant. A PTA is less commonly performed because only a relatively small percentage of insulin-dependent patients truly have brittle diabetes that cannot be controlled despite their own best efforts and the help of diabetologists, endocrinologists, and other health professionals. In general, PTA candidates have not yet developed advanced secondary complications of diabetes; yet, halting the development or progression of such complications significantly improves both quality of life and life expectancy (more so for PTA recipients than for SPK or PAK recipients).
PTA recipients, in addition to the surgical risk of the pancreas transplant procedure itself, also incur the risk of immunosuppressive therapy (in the absence of a transplanted kidney graft). Immunosuppression in PTA recipients is required to prevent rejection (in order to establish insulin independence), to avoid hypoglycemic episodes, and to prevent the progression of secondary diabetes complications. Because of the required immunosuppressive therapy and its side effects—in the absence of advanced diabetic nephropathy—the PTA option has not been widely accepted. Moreover, in the first two decades after the first PTA was performed in 1968, its surgical risk was high, with considerable technical morbidity and poor outcomes. Only after the introduction of calcineurin inhibitors (and, specifically, tacrolimus) did the immunologic graft failure rates significantly decrease in PTA recipients. Despite improvements in exogenous insulin therapy, including the use of devices such as insulin pumps, the risk of hypoglycemic episodes (and their detrimental side effects) remains substantial in patients with brittle diabetes.
We present herein the significantly improved PTA results as reported to the International Pancreas Transplant Registry (IPTR) over a 43-year period.
Diabetes Care. 2013;36(8):2440-2447. © 2013 American Diabetes Association, Inc.