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Raeisi-Dehkordi, H.* ; Thorand, B. ; Beigrezaei, S.* ; Peters, A. ; Rathman, W.* ; Adamski, J. ; Chatelan, A.* ; van der Schouw, Y.T.* ; Franco, O.H.* ; Muka, T.* ; Nano, J.

The mediatory role of androgens on sex differences in glucose homeostasis and incidence of type 2 diabetes: The KORA study.

Cardiovasc. Diabetol. 23:411 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Sex differences exist in type 2 diabetes (T2D), and androgens have been implicated in the etiology of T2D in a sex-specific manner. We therefore aimed to investigate whether androgens play a role in explaining sex differences in glucose homeostasis and incidence of T2D. METHODS: We used observational data from the German population-based KORA F4 study (n = 1975, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1412). T2D was determined through self-reporting and confirmed by contacting the physicians and/or reviewing the medical charts. Multivariable linear and logistic regression models were employed to explore associations. Mediation analyses were performed to assess direct effects (DE) and indirect effects (IE), and the mediating role of androgens (total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAs)) in the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). RESULTS: After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower levels of TT, DHEAs, fasting glucose levels, fasting insulin levels, 2 h-glucose levels and HOMA-IR, compared to men. An inverse association was observed for TT and glucose- and insulin-related traits in men, while a positive association was observed for TT and fasting glucose levels in women. We found a mediatory role of TT on the association of sex with fasting glucose levels (IE: β = 3.08, 95% CI: 2.04, 4.30), fasting insulin levels (IE: β = 0.39, 95% CI:0.30, 0.47), 2 h-glucose levels (IE: β = 12.77, 95% CI: 9.01, 16.03) and HOMA-IR (IE: β = 0.41, 95% CI: 0.33, 0.50). Also, the inconsistent mediatory role of TT was seen on the association of sex with incidence of T2D (DE: 0.12, 95% CI: 0.06, 0.20 and IE: OR = 7.60, 95% CI: 3.43, 24.54). The opposing DE and IE estimates suggest that the association between sex and either glucose homeostasis or the incidence of T2D may differ when TT is considered as a potential mediator, with higher TT levels being beneficial for glucose metabolism or incidence of T2D in men, while in women, detrimental. No mediatory role was observed for either DHEA or DHEAs on glucose homeostasis or the incidence of T2D. CONCLUSIONS: The dimorphic mediatory role of TT highlights its complex role in metabolic health, contributing differently to the glucose dysregulation and risk of T2D in men and women.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Androgens ; Glycemic Control ; Mediation Analysis. ; Sex Differences ; Sex Hormones ; Type 2 Diabetes; Serum Dehydroepiandrosterone-sulfate; Hormone-binding Globulin; Necrosis-factor-alpha; Insulin-resistance; Testosterone Replacement; Older Men; Inflammatory Cytokines; Gender-differences; Risk; Women
ISSN (print) / ISBN 1475-2840
e-ISSN 1475-2840
Quellenangaben Band: 23, Heft: 1, Seiten: , Artikelnummer: 411 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen Swiss National Science Foundation
University Hospital of Augsburg
State of Bavaria. Data collection in the KORA
Helmholtz Zentrum Muenchen- German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)