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

Abstract

OBJECTIVE Posttransplantation 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. RESEARCH DESIGN AND METHODS We conducted a post hoc analyses of a prospective single-center cohort study including adult male KTR with a functioning graft ≥1 year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry. Development of PTDM was defined according to the American Diabetes Association’s criteria. RESULTS We included 243 male KTR (aged 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 HbA1c (hazard ratio [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). CONCLUSIONS Our results suggest that low androgen levels are a novel potential modifiable risk factor for the development of PTDM in male KTR.