The Impact of New Onset Post-Transplant Diabetes on Outcomes after Heart Transplantation

Purpose Diabetes mellitus (DM) is common amongst heart transplant (HT) recipients and may occur either pre-HT or as new onset DM post-HT. We sought to define the incidence of pre-HT and post-HT DM in the contemporary era, evaluate predictors of post-HT DM, and assess the impact of post-HT DM on major clinical outcomes. Methods This is an ISHLT Transplant Registry study of adult primary HT-alone recipients between Jan 1995 and June 2012 without missing pre- or post-HT DM status, who survived to 1 year post-HT. DM status was characterized as (1) No DM pre- or post-HT; (2) Pre-HT DM; or (3) Post-HT DM (onset within 5 years of HT). Kaplan-Meier curves were constructed for post-HT DM onset. Multivariable Cox proportional hazards models were constructed to assess risk factors for post-HT DM onset, as well as risk factors for development of subsequent severe renal dysfunction and death/re-transplantation. Results Of 26,263 eligible subjects, 57% had no DM pre- or post-HT, 22% had pre-HT DM, and 21% had new onset post-HT DM. Most cases of new-onset DM occurred during the first year post-HT, with equivalent incidence between eras in the unadjusted analysis (Figure). In adjusted analyses, onset of post-HT DM was associated with tacrolimus (vs cyclosporine), as well as with female sex, ischemic cardiomyopathy, pre-HT dialysis and steroids; subjects with pre-HT MCS had a lower hazard of post-HT DM. In patients without pre-HT DM, post-HT DM within 5 years was associated with an increased risk of subsequent severe renal dysfunction and death/re-transplantation, compared to patients without post-HT DM (HR 1.89; 1.77- 2.01 and HR 1.39; 1.32-1.45, respectively). Conclusion Pre- and post-HT DM are both common in the contemporary era. Post-HT DM is associated with increased risk of severe renal dysfunction and death or re-transplantation. Sodium-glucose cotransporter (SGLT)-2 inhibitors, a DM medication class that reduces renal dysfunction and cardiovascular events, should be tested as a novel strategy to improve survival in HT recipients.