Hyperglycemia following pancreas transplantation: Rethinking graft function and metabolic control.

Pancreas transplantation (PTX) is the single most effective therapeutic option to restore sustained euglycemia and insulin independence in patients with insulin-requiring diabetes mellitus; however, recurrence of hyperglycemia and diabetes mellitus after PTX may occur. In this personal viewpoint, we propose a practical diagnostic and management framework for posttransplant diabetes mellitus (PTDM) and its distinction from pancreas graft failure (PGF) and other causes of hyperglycemia after PTX. PTDM after PTX is a distinct clinical entity from PGF, defined as persistent hyperglycemia in recipients with a functioning pancreas graft in the absence of rejection, infection, or technical complication. Diagnosis should be made after stabilization of immunosuppressive therapy and excludes transient posttransplant hyperglycemia. Risk factors for PTDM include older donor age, recipient obesity, high pretransplant insulin usage, posttransplant weight gain, and use of immunosuppressive agents such as tacrolimus and glucocorticoids. PTDM can mimic PGF and may be associated with adverse outcomes. Pharmacologic management includes metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, or insulin. Multidisciplinary care, including endocrinology support, is essential. Weight management strategies, including bariatric surgery in some cases, may benefit select patients.