Androgens and Development of Posttransplantation Diabetes Mellitus in Male Kidney Transplant Recipients: A Post Hoc Analysis of a Prospective Study

<u>Objective.</u><b> </b>Post-transplantation Diabetes Mellitus (PTDM) effects up to 30% of all kidney transplant recipients (KTR). Recent studies in mice found that sufficient androgen levels are necessary for β-cell health and adequate insulin secretion. This raises the question whether a similar relationship might be present in KTR. Hence, we hypothesized that dihydrotestosterone and testosterone are associated with the development of PTDM in male KTR. <p><u>Research design and Methods.</u><b> </b>We conducted a post-hoc analyses of a prospective single-center cohort study including adult male KTR with a functioning graft ≥1 year post-transplantation. Androgen levels were assessed by liquid chromatography tandem mass spectrometry. Development of PTDM was defined according to the American Diabetes Association’s criteria. </p> <p><u>Results.</u><b> </b>We included 243 male KTR (age 51 ± 14 years), with a median dihydrotestosterone 0.9 [0.7–1.3] nmol/L and testosterone of 12.1 [9.4–15.8] nmol/L. During 5.3 [3.7–5.8] years of follow-up, 28 KTR (11.5%) developed PTDM. A clear association was observed as 15 (19%), 10 (12%), and 3 (4%) male KTR developed PTDM in the respective tertiles of dihydrotestosterone (P=0.008). In Cox regression analyses, both dihydrotestosterone and testosterone as continuous variables, were inversely associated with the risk to development PTDM, independent of glucose and HbA_1c (HR 0.31; 95%CI[0.16–0.59], P<0.001 and HR 0.32; 95%CI[0.15–0.68], P=0.003 respectively). </p> <p><u>Conclusions.</u> Our results suggest that low androgen levels are a novel potential modifiable risk factor for the development of PTDM in male KTR. </p>