Guixue Guan, Yifu Pu, Xiaofeng Tang, Qian Sun, Yuan Gao, Wen Yang, Conghui Han, Zuobin Zhu
Department of Gynecology, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
Department of Gynecology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu, China.
Front Endocrinol (Lausanne). 2024 Feb 5;15:1337562. doi: 10.3389/fendo.2024.1337562. eCollection 2024.
Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM.
The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome.
The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method.
We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS.
确定多囊卵巢综合征（PCOS）与妊娠期糖尿病（GDM）之间的因果关系对GDM的预防和治疗具有重要意义。尽管众多观察性研究表明PCOS与GDM之间存在关联，但这两种疾病之间是否存在明确的因果关系以及PCOS的哪些特定特征导致GDM发病率增加仍不清楚。
基于全基因组关联研究（GWAS）的公开统计数据，采用两样本孟德尔随机化研究，调查多囊卵巢综合征（PCOS）及其特征指标与妊娠期糖尿病（GDM）之间的因果关系。采用逆方差加权法作为主要分析方法，检验PCOS及其特征指标与GDM之间的关联。MR Egger截距用于评估多效性，而Q值及其相应的P值用于评估异质性。需要注意的是，本研究采用两样本MR设计，其中PCOS及其特征指标被视为暴露因素，而GDM被视为结局。
研究结果表明，PCOS与GDM之间不存在因果关系（所有方法P>0.05，OR值的95%CI通过1）。IVW OR值为1.007，95%CI为0.906至1.119，P值为0.904。此外，MR Egger Q值为8.141，P值为0.701，IVW Q值也为8.141，P值为0.774，表明无显著异质性。另外，MR Egger截距为0.0004，接近零，P值为0.988，表明无多效性。然而，该研究确实发现，基于IVW方法，睾酮、高密度脂蛋白、性激素结合球蛋白、体重指数、腰臀比、载脂蛋白A-I、子女数量、母亲、父亲和兄弟姐妹的糖尿病病史、糖化血红蛋白、空腹胰岛素、空腹血糖、受教育年限等其他因素与GDM之间存在因果关系。
我们观察到遗传预测的PCOS与GDM风险之间无关联，这意味着PCOS本身不会增加患GDM的易感性。睾酮、高密度脂蛋白和性激素结合球蛋白等其他与PCOS相关的因素可能阐明PCOS与GDM之间的联系。基于这些发现，针对PCOS患者预防GDM的努力应优先考虑具有高危特征的个体，而非涵盖所有PCOS女性。
