Khatami Farnaz, Lange Theis, Groothof Dion, Ahanchi Noushin Sadat, Quezada-Pinedo Hugo G, Raeisi-Dehkordi Hamidreza, De Borst Martin H, Vidal Pedro-Marques, Sailesh Mohan, Prabhakaran Dorairaj, Bano Arjola, Bakker Stephan J L, Muka Taulant, Eisenga Michele F
Institute of Social and Preventive Medicine (ISPM), University of Bern, 3012 Bern, Switzerland.
Graduate School for Health Sciences, University of Bern, 3012 Bern, Switzerland.
J Endocr Soc. 2024 May 16;8(7):bvae098. doi: 10.1210/jendso/bvae098. eCollection 2024 May 23.
Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain.
In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D.
We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed.
The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (β = -.01; 95% CI -0.02, -0.01) and FPI (β = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin.
Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed.
已有报道称2型糖尿病（T2D）的患病率和发病率存在性别差异，但其潜在机制尚不确定。
在本研究中，我们旨在调查铁生物标志物是否介导了生物性别与糖代谢及T2D发病率之间的关联。
我们使用了来自荷兰格罗宁根前瞻性肾脏和血管终末期疾病预防研究中纳入的普通人群的数据。我们测量了铁蛋白、转铁蛋白饱和度（TSAT）、铁调素、可溶性转铁蛋白受体（sTfR）、空腹血糖（FPG）、空腹血浆胰岛素（FPI）水平以及T2D的发病率。我们使用多变量回归和中介分析来检验我们的假设。所有铁生物标志物、FPG和FPI均进行对数转换。
5312名个体（51.3%为女性）的平均（标准差）年龄为52.2（11.6）岁。与男性相比，女性的FPG（β = -0.01；95%CI -0.02，-0.01）和FPI（β = -0.03；95%CI -0.05，-0.02）水平较低。铁蛋白、铁调素和sTfR对性别与FPG之间的关联分别显示出21%、5%和7.1%的潜在中介作用。此外，这些变量分别介导了性别与FPI之间关联的48.6%、5.7%和3.1%。另外，TSAT在性别与FPG和FPI的关联中具有抑制性中介作用。女性的T2D发病率低于男性（风险比0.58；95%CI 0.44，0.77），其中19.2%的差异由铁蛋白介导。
铁生物标志物可能部分介导了性别与葡萄糖稳态之间的关联。需要进一步的研究来探讨我们研究结果的因果关系。
