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

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posted on 05.10.2021, 16:23 by Suzanne P. Stam, Sara Sokooti, Michele F. Eisenga, Anna van der Veen, Antonio W. Gomes-Neto, Peter R. van Dijk, Jelmer J. van Zanden, Michel J. Vos, Ido P. Kema, André P. van Beek, Stephan J. Bakker, TransplantLines Investigators
Objective. 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.

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 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.

Results. 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 HbA1c (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.

Funding

The TransplantLines Food and Nutrition Biobank and Cohort Study (clinical trial reg. no. NCT02811835, ClinicalTrials.gov) was established using funds by the Top Institute Food and Nutrition. Additionally, this study was (partly) funded by “The European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement 754425

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