绝经过渡期女性血清内源性性激素介导体质量指数与糖尿病的关联：一项纵向队列研究。
Association between Body Mass Index and Diabetes Mellitus Are Mediated through Endogenous Serum Sex Hormones among Menopause Transition Women: A Longitudinal Cohort Study.
机构信息
Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Institute for Medical Dataology, Shandong University, Jinan 250002, China.
出版信息
Int J Environ Res Public Health. 2023 Jan 19;20(3):1831. doi: 10.3390/ijerph20031831.
OBJECTIVE
To explore whether and to what extent endogenous sex hormones mediate the association between overweight and diabetes risk in menopausal transition women.
METHODS
Premenopausal women were from the Study of Women's Health Across the Nation, with measurements of serum sex hormone including sex hormone binding globulin (SHBG), testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and dehydroepiandrosterone sulfate (DHAS) in first postmenopausal follow-up. At the last postmenopausal follow-up, hyperglycemia status was confirmed. The partial least squares (PLS) regression method was used to extract hormonal signals associated with body mass index (BMI). Hyperglycemia was defined as individuals with prediabetes or diabetes; overweight was defined as BMI ≥ 25 kg/m. Causal mediation analysis was used to examine the mediation effect on the association between perimenopause overweight and post-menopause hyperglycemia through PLS score and individual sex hormones.
RESULTS
The longitudinal study included 1438 normal glucose women with a baseline mean age (SD) of 46.5 (2.6) years and a mean follow-up period of 9.9 years. During the follow-up period, 145 (10.1) cases of hyperglycemia occurred. Compared with normal-weight participants, overweight women were associated with a higher hyperglycemia risk during the transition period (OR = 4.06, 95% CI: 2.52 to 6.80). Overweight women had higher T, E2, and lower SHBG, FSH, and DAHS concentrations (β = 0.26, 0.38, -0.52, -0.52, and -0.13, < 0.05 for all). After adjusting for overweight and covariates, lower SHBG and FSH levels were associated with higher hyperglycemia risk (OR = 0.70 and 0.69, all < 0.05). As a linear combination of sex hormones, the PLS score was positively associated with T, E2, and negatively with SHBG, FSH, and DHAS. PLS score interpreted 36.50% ( < 0.001) of the overweight-hyperglycemia association. Considering single-sex hormones, the mediation proportion of SHBG and FSH were 21.38% ( < 0.001) and 24.08% ( < 0.001).
CONCLUSIONS
Sex hormones mediated the association of overweight and diabetes risk in menopause transition women. SHBG and FSH have the dominant mediation effect.
目的
探讨内源性性激素是否以及在何种程度上介导了绝经过渡期女性超重与糖尿病风险之间的关联。
方法
本研究纳入了来自全国妇女健康研究的绝经前女性，在首次绝经后随访时测量了包括性激素结合球蛋白 (SHBG)、睾酮 (T)、雌二醇 (E2)、卵泡刺激素 (FSH) 和硫酸脱氢表雄酮 (DHAS) 在内的血清性激素水平。在最后一次绝经后随访时，确定了高血糖状态。采用偏最小二乘 (PLS) 回归方法提取与体重指数 (BMI) 相关的激素信号。将高血糖定义为患有糖尿病前期或糖尿病的个体；超重定义为 BMI≥25kg/m。采用因果中介分析方法，通过 PLS 评分和个体性激素，检验绝经前超重与绝经后高血糖之间关联的中介效应。
结果
本纵向研究纳入了 1438 名血糖正常的女性，基线平均年龄（标准差）为 46.5（2.6）岁，平均随访时间为 9.9 年。在随访期间，有 145 例（10.1%）发生高血糖。与体重正常的参与者相比，超重女性在过渡期间发生高血糖的风险更高（OR=4.06，95%CI：2.52 至 6.80）。超重女性的 T、E2 浓度较高，SHBG、FSH 和 DAHS 浓度较低（β=0.26、0.38、-0.52、-0.52 和-0.13，均 <0.05）。在调整了超重和混杂因素后，较低的 SHBG 和 FSH 水平与较高的高血糖风险相关（OR=0.70 和 0.69，均 <0.05）。作为性激素的线性组合，PLS 评分与 T、E2 呈正相关，与 SHBG、FSH 和 DHAS 呈负相关。PLS 评分解释了超重与高血糖关联的 36.50%（<0.001）。考虑到单个性激素，SHBG 和 FSH 的中介比例分别为 21.38%（<0.001）和 24.08%（<0.001）。
结论
性激素介导了绝经过渡期女性超重与糖尿病风险之间的关联。SHBG 和 FSH 具有主要的中介作用。
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