Testosterone levels and the development of posttransplantation diabetes mellitus in male renal transplant recipients

S.P. Stam, M.F. Eisenga, A. van der Veen, J.J. van Zanden, S.J.L. Bakker, I.P. Kema, A.P. van Beek

Thursday 5 march 2020

14:50 - 15:00h at Leo Franssen zaal

Parallel session: Parallel sessie XIV– Klinische abstracts

Background: Despite major improvements in outcomes, male renal transplant recipients (RTR) remain predisposed to numerous mortality risk factors, including low levels of testosterone and development of Posttransplantion Diabetes Mellitus (PTDM). These latter two risk factors have recently been linked in male mice models, uncovering that sufficient testosterone levels are required for adequate insulin secretion and bèta cell health. This raises the question whether a similar relationship can be observed in RTR. Hence, we hypothesized that low levels of testosterone are associated with the development of PTDM in male RTR.

Methods: We conducted a single-center prospective cohort study including adult male RTR with a function graft ≥ 1 year post-transplantation. Androgen levels were assessed by liquid chromatography tandem mass spectrometry. The development of PTDM was defined according to the American Diabetes Association’s diagnostic criteria for diabetes. Cox proportional hazard regression analyses models were utilized to assess the association between testosterone and development of PTDM.

Results: We included 257 male RTR (age 51±14 years), with median [interquartile range] levels of testosterone of 12.0 [9.4–15.7] nmol/L. During 5.3 [3.7–5.8] years of follow-up, 32 RTR developed PTDM. In univariable Cox regression analyses, we found an inverse association between testosterone as continuous variable and the risk for development of PTDM (HR 0.45; 95%CI 0.31–0.66; P<0.001). In multivariable analyses, the association remained, independent of adjustment for age, eGFR, glucose levels, and HbA1c (HR 0.49; 95%CI0.29–0.83; P=0.008). In Cox regression analyses according to tertiles of the distribution of testosterone, we obtained similar results, with RTR in the lowest tertile, with testosterone levels of 8.4 [7.2–9.4] nmol/L, having an independently increased risk for the development of PTDM (HR 4.16; 95%CI 1.15–14.98; P=0.03), as compared to RTR in the highest tertile, with testosterone levels of 17.3 [15.7–20.7] nmol/L.

Conclusions: Our results demonstrate that low post-transplantation testosterone levels in males are independently associated with an increased risk for development of PTDM. This finding offers new insights to strategies to prevent late development of PTDM in male RTR.