Xing Wenguo, Lv Quanjun, Li Yuqian, Wang Chongjian, Mao Zhenxing, Li Yan, Li Jia, Yang Tianyu, Li Linlin
Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Department of Nutrition, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Nutr Metab Cardiovasc Dis. 2023 Apr;33(4):873-882. doi: 10.1016/j.numecd.2023.01.011. Epub 2023 Jan 29.
The relationship between reproductive factors and type 2 diabetes (T2D) is controversial; therefore, we explored the causal relationship of age at menarche (AAM), age at natural menopause (ANM), with the risk of T2D and glycemic traits using two-sample Mendelian randomization.
We used publicly available data at the summary level of genome-wide association studies, where AAM (N = 329,345), ANM (N = 69,360), T2D (N = 464,389). The inverse variance weighting (IVW) method was employed as the primary method. To demonstrate the robustness of the results, we also conducted various sensitivity analysis methods including the MR-Egger regression, the weighted median (WM) and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. After excluding IVs associated with confounders, we found a causal association between later AAM and reduced risk of T2D (OR 0.81 [95% CI 0.75, 0.87]; P = 2.20 × 10), lower levels of FI (β -0.04 [95% CI -0.06, -0.01]; P = 2.19 × 10), FPG (β -0.03 [95% CI -0.05, -0.007]; P = 9.67 × 10) and HOMA-IR (β -0.04 [95% CI -0.06, -0.01]; P = 4,95 × 10). As for ANM, we only found a causal effect with HOMA-IR (β -0.01 [95% CI -0.02, -0.005]; P = 1.77 × 10), but not with T2D.
Our MR study showed a causal relationship between later AAM and lower risk of developing T2D, lower FI, FPG and HOMA-IR levels. This may provide new insights into the prevention of T2D in women.
生殖因素与2型糖尿病（T2D）之间的关系存在争议；因此，我们使用两样本孟德尔随机化方法探讨了初潮年龄（AAM）、自然绝经年龄（ANM）与T2D风险及血糖特征之间的因果关系。
我们使用了全基因组关联研究汇总水平的公开可用数据，其中AAM（N = 329,345）、ANM（N = 69,360）、T2D（N = 464,389）。采用逆方差加权（IVW）方法作为主要方法。为了证明结果的稳健性，我们还进行了各种敏感性分析方法，包括MR-Egger回归、加权中位数（WM）和MR多效性残差和异常值（MR-PRESSO）检验。在排除与混杂因素相关的IVs后，我们发现AAM较晚与T2D风险降低之间存在因果关系（OR 0.81 [95% CI 0.75, 0.87]；P = 2.20×10），空腹胰岛素（FI）水平较低（β -0.04 [95% CI -0.06, -0.01]；P = 2.19×10），空腹血糖（FPG）较低（β -0.03 [95% CI -0.05, -0.007]；P = 9.67×10）和稳态模型评估胰岛素抵抗（HOMA-IR）较低（β -0.04 [95% CI -0.06, -0.01]；P = 4.95×10）。至于ANM，我们仅发现与HOMA-IR存在因果效应（β -0.01 [95% CI -0.02, -0.005]；P = 1.77×10），但与T2D不存在因果关系。
我们的孟德尔随机化研究表明，AAM较晚与发生T2D的风险较低、FI、FPG和HOMA-IR水平较低之间存在因果关系。这可能为女性T2D的预防提供新的见解。
