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

Abstract

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. 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. 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 (<i>P</i> = 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 (hazard ratio [HR] 0.31 [95% CI 0.16-0.59], <i>P</i> < 0.001; and HR 0.32 [95% CI 0.15-0.68], <i>P</i> = 0.003, respectively). Our results suggest that low androgen levels are a novel potential modifiable risk factor for the development of PTDM in male KTR.