*

A complete list of the TransplantLines Investigators can be found in the appendix.

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.

Clinical trial reg. no. NCT02811835, clinicaltrials.gov

This article contains supplementary material online at https://doi.org/10.2337/figshare.16566963.

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