Department of Public Health and Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
Department of Epidemiology and Health Statistics, School of Public Health, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Nutrients. 2024 Aug 7;16(16):2603. doi: 10.3390/nu16162603.
Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials.
Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk.
Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR-Egger, maximum likelihood, weighted median, and weighted mode.
The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran's Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), = 0.408].
According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required.
许多研究都探讨了维生素 D 是否与妊娠糖尿病（GDM）有关。然而，由于观察性研究和随机对照试验存在诸多缺陷，确定其因果关系仍然具有挑战性。
采用双样本 Mendelian 随机化（MR）研究 25-羟维生素 D（25（OH）D）和维生素 D 结合蛋白（VDBP）与 GDM 风险之间的潜在因果关系。
使用来自独立队列的公开可用汇总数据进行双样本 MR。对于 25（OH）D，我们从英国生物库、IEU 和 EBI 获得数据，然后通过 METAL 进行荟萃分析以增强统计效力；对于 VDBP，数据来自 INTERVAL 研究；对于 GDM，数据来自 FinnGen。采用逆方差加权（IVW）法作为主要分析方法，并进行了几项敏感性分析，如 MR-Egger、最大似然、加权中位数和加权众数。
IVW 结果显示 25（OH）D 与 GDM 风险之间存在微弱的负向因果关系[比值比（95%置信区间）= 0.71（0.50，0.99），P=0.046]。然而，根据敏感性分析，因果关系不稳定，Cochran's Q 检验显示存在显著异质性。去除与 BMI 相关的 IV 后，25（OH）D 与 GDM 之间的因果关系消失[比值比（95%置信区间）= 0.76（0.55，1.06），P=0.101]。此外，我们的研究没有证据支持 VDBP 水平与 GDM 风险之间存在因果关系的假设[比值比（95%置信区间）= 0.98（0.93，1.03），P=0.408]。
根据本研究，发现 25（OH）D 与 GDM 风险之间存在微弱的负向因果关系，而我们几乎没有证据支持 VDBP 与 GDM 之间的关联。为了进一步探讨总 25（OH）D 或游离 25（OH）D 水平与 GDM 是否存在因果关系，需要关注育龄女性和其他种族群体的 GWAS 数据。
