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

作者：Hamidreza Raeisi‐Dehkordi, Barbara Thorand, Sara Beigrezaei, Annette Peters, Wolfgang Rathman, Jerzy Adamski, Angéline Chatelan, Yvonne T. van der Schouw, Oscar H. Franco, Taulant Muka, Jana Nano · 发表于：Cardiovascular Diabetology · 年份：2024 · DOI：10.1186/s12933-024-02494-7 · 被引用次数：10 · 研究领域：Hormonal and reproductive studies、Sexual Differentiation and Disorders、Sex and Gender in Healthcare

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 ...