Department of Blood Transfusion, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Department of Blood Transfusion, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
Front Endocrinol (Lausanne). 2024 Mar 11;15:1357279. doi: 10.3389/fendo.2024.1357279. eCollection 2024.
Diabetes mellitus (DM) stands as the most prevalent endocrine abnormality affecting the physiological systems and organs and impairing the male reproductive functions. Type 2 Diabetes Mellitus (T2DM), accounting for about 90-95% of DM, is closely associated with male infertility. However, the magnitude of the causal relationships between T2DM and male infertility remains unclear. The current investigation was to explore the causal relationship between T2DM and male infertility utilizing the Mendelian Randomization (MR) analysis.
A two-sample MR (2SMR) analysis was conducted to investigate the causal relationship between T2DM and male infertility in the European population from the genome-wide association study (GWAS) summary data that was publicly accessible. GWAS for T2DM and male infertility were extracted from the IEU Open GWAS Project database, with the resulting data encompassing 680 cases and 72,799 controls as the outcome data. Five MR methods were employed for the 2SMR analyses, namely the MR-Egger, weighted median estimation (WME), weighted mode (WM), inverse-variance weighted (IVW), and simple mode. The primary analytical technique utilized in this study was the IVW method, and a multivariate MR analysis was executed to examine the potential mediating influences of T2DM on male infertility.
Following were the odds ratios (ORs) and associated 95% CIs derived from IVW (fixed effects), MR-Egger, WM, WME, and simple mode approaches: 0.824 (95% CI 0.703-0.966), 0.726 (95% CI 0.527-1.001), 0.827 (95% CI 0.596-1.150), 0.841 (95% CI 0.654-1.082), and 0.875 (95% CI 0.544-1.405), respectively. The outcomes of the heterogeneity tests were =0.378 and =0.384, respectively, implying no heterogeneity. Egger-intercept outcomes were =0.374, highlighting the absence of pleiotropy. The stability of the results was affirmed through the leave-one-out analysis. Notably, all values surpassed 10, indicating the absence of weak bias attributed to instrument variables(IVs).
This research furnishes evidence supporting a causal association between T2DM and male infertility. These insights offer a foundation for future investigations aiming to establish the association between genetically predicted T2DM and male infertility. These outcomes suggest the significance of active monitoring and proactive measures for preventing infertility in male individuals with T2DM. Furthermore, careful consideration is required for individuals of reproductive age to prevent and treat T2DM.
糖尿病（DM）是一种最常见的影响生理系统和器官的内分泌异常，会损害男性生殖功能。2 型糖尿病（T2DM）占糖尿病的 90-95%，与男性不育密切相关。然而，T2DM 与男性不育之间的因果关系的程度仍不清楚。本研究旨在利用孟德尔随机化（MR）分析探讨 T2DM 与男性不育之间的因果关系。
采用两样本 MR（2SMR）分析，从公开的全基因组关联研究（GWAS）汇总数据中研究欧洲人群中 T2DM 和男性不育之间的因果关系。从 IEU Open GWAS 项目数据库中提取 T2DM 和男性不育的 GWAS 数据，结果数据包含 680 例病例和 72799 例对照作为结局数据。采用 5 种 MR 方法进行 2SMR 分析，即 MR-Egger、加权中位数估计（WME）、加权模式（WM）、逆方差加权（IVW）和简单模式。本研究的主要分析技术是 IVW 方法，并进行了多变量 MR 分析，以检验 T2DM 对男性不育的潜在中介影响。
IVW（固定效应）、MR-Egger、WM、WME 和简单模式方法得出的优势比（OR）和相关 95%置信区间（CI）分别为：0.824（95%CI 0.703-0.966）、0.726（95%CI 0.527-1.001）、0.827（95%CI 0.596-1.150）、0.841（95%CI 0.654-1.082）和 0.875（95%CI 0.544-1.405）。异质性检验的结果分别为 =0.378 和 =0.384，表明没有异质性。Egger 截距结果分别为 =0.374，表明没有偏倚。通过逐一剔除分析证实了结果的稳定性。值得注意的是，所有值都超过了 10，表明由于工具变量（IVs）引起的弱偏倚不存在。
本研究提供了 T2DM 与男性不育之间存在因果关系的证据。这些结果为进一步研究建立遗传预测的 T2DM 与男性不育之间的关联提供了基础。这些结果表明，对于 T2DM 男性个体，积极监测和主动采取措施预防不育至关重要。此外，对于有生育能力的个体，需要谨慎考虑预防和治疗 T2DM。
