Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. We used observational data from the German population-based KORA F4 study (n = 1937, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1387). T2D was initially assessed by self-report and validated by contacting the physicians and/ or reviewing the medical charts. Mediation analyses were performed to assess the role of SHBG in mediating the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower fasting glucose levels compared to men (β = -4.94 (mg/dl), 95% CI: -5.77, -4.11). SHBG levels were significantly higher in women than in men (β = 0.47 (nmol/l), 95% CI:0.42, 0.51). Serum SHBG may mediate the association between sex and fasting glucose levels with a proportion mediated (PM) of 30% (CI: 22–41%). Also, a potential mediatory role of SHBG was observed for sex differences in incidence of T2D (PM = 95% and 63% in models 1 and 2, respectively). Our novel findings suggest that SHBG may partially explain sex-differences in glucose control and T2D incidence.

研究表明，性激素结合球蛋白 (SHBG) 与葡萄糖稳态相关，可能在 2 型糖尿病 (T2D) 的病因学中发挥作用。目前尚不清楚性激素结合球蛋白 (SHBG) 是否可能介导血糖控制的性别差异以及随后的 T2D 发病率。我们使用了基于德国人群的 KORA F4 研究（ n = 1937，平均年龄：54 岁，41% 女性）及其随访检查 KORA FF4（中位随访 6.5 年， n = 1387）的观察数据。 T2D 最初通过自我报告进行评估，并通过联系医生和/或查看病历进行验证。进行中介分析以评估性激素结合球蛋白 (SHBG) 在中介性别（女性与男性）、葡萄糖和胰岛素相关性状（横断面分析）以及 T2D 发病率（纵向分析）之间的关联中的作用。调整混杂因素后（模型 1：根据年龄调整；模型 2：模型 1 + 吸烟 + 饮酒 + 体力活动），与男性相比，女性的空腹血糖水平较低 (β = -4.94 (mg/dl)，95% CI：-5.77，-4.11）。女性的 SHBG 水平显着高于男性（β = 0.47 (nmol/l)，95% CI：0.42，0.51）。血清 SHBG 可能介导性别和空腹血糖水平之间的关联，介导比例 (PM) 为 30%（CI：22-41%）。此外，还观察到 SHBG 对 T2D 发病率的性别差异具有潜在的中介作用（模型 1 和模型 2 中 PM 分别为 95% 和 63%）。我们的新发现表明性激素结合球蛋白（SHBG）可以部分解释血糖控制和 T2D 发病率的性别差异。