Stratifying Post-Transplant Diabetes: Prognostic Impact of Insulin Dependence and Treatment Duration

Abstract

Background Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after kidney transplantation. However, its long-term prognostic impact may vary depending on the persistence and intensity of treatment. This study aimed to evaluate whether insulin-dependent PTDM persisting beyond 12 months is associated with adverse outcomes and whether stratifying PTDM phenotypes is clinically meaningful.

Methods We conducted a retrospective cohort study of adult kidney transplant recipients (2010–2021) with systematic follow-up through 2023. PTDM was classified into four phenotypes: Early post-transplant hyperglycemia (PTH), transient (<12 months), persistent oral-treated, and persistent insulin-treated (>12 months). Primary outcomes were patient and death-censored graft survival; secondary outcomes included cardiovascular events and diabetes-related complications. Multivariable logistic regression was used to identify independent predictors of mortality.

Results A total of 346 kidney transplant recipients were included, with a median follow-up of 8.9 years. Persistent insulin-treated PTDM was present in 33.8% of patients and was independently associated with increased mortality [odds ratio (OR) = 2.12; 95% confidence interval (95% CI): 1.02–4.40; p = 0.043], and age. Patient survival at 10 years was significantly lower in this group (74.0%) compared to Early PTH (85.5%, p = 0.021), while graft survival remained similar across groups. No significant associations were found between PTDM phenotypes and retinopathy, cerebrovascular events, or diabetic nephropathy. Definitive steroid withdrawal was associated with reduced mortality (OR = 0.37; p = 0.012). Although SGLT2 inhibitor use did not reach statistical significance in adjusted models, none of the treated patients died during follow-up, compared to 19.8% mortality in non-users (p = 0.013, in univariate analysis).

Conclusion Persistent insulin-treated PTDM is independently associated with poorer survival. Stratifying PTDM by phenotype helps identify high-risk patients who may benefit from closer follow-up and cardiometabolic optimization.