Post-Transplant Diabetes Mellitus Requiring Insulin Identifies High-Risk Outcomes After Solid Organ Transplantation.

Abstract

Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, but its long-term prognostic significance and the clinical implications of post-transplant antidiabetic treatment patterns remain incompletely understood. We aimed to evaluate PTDM incidence, determinants, treatment patterns, and associated long-term outcomes using large-scale real-world data. We analyzed adult solid organ transplant recipients without pre-existing diabetes within the TriNetX Global Collaborative Network (2006-2024). PTDM incidence and risk factors were assessed using time-to-event analyses. Clinical outcomes were evaluated using propensity score-matched cohorts. Antidiabetic treatment patterns were characterized using treatment pathway analyses, and outcomes were compared according to insulin versus non-insulin-based management among recipients with PTDM. Among 263,325 recipients, PTDM incidence increased over time and varied markedly by transplanted organ, transplant era, and geographic region. Older age, male sex, adiposity, baseline dysglycaemia, dyslipidaemia, reduced renal function, and immunosuppressive exposure were independently associated with PTDM. After matching, PTDM was associated with higher long-term risks of mortality, graft failure, graft rejection, cardiovascular events, infections, malignancies, and renal-metabolic complications, while early post-transplant risks were largely comparable. Antidiabetic treatment patterns were heterogeneous and organ-specific. Insulin-treated PTDM recipients experienced substantially worse graft and patient outcomes than non-insulin-treated recipients, despite similar long-term glycaemic control, indicating that insulin requirement identifies a high-risk metabolic phenotype. Findings were consistent in single organ transplant-specific sensitivity analyses. PTDM acts as a chronic modifier of long-term outcomes after solid organ transplantation. Insulin-treated PTDM identifies a subgroup at particularly high risk, underscoring the need for improved metabolic risk stratification and tailored management strategies in transplant recipients.