State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Department of Maternal, Child and Adolescent Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Environ Health. 2024 Oct 12;23(1):84. doi: 10.1186/s12940-024-01128-5.
Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce.
The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways.
As parameterized in tertiles, titanium showed positive dose-response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk.
In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk.
最近的几项研究报告了钛暴露对非孕妇群葡萄糖稳态的潜在不良影响，但钛暴露与妊娠期糖尿病（GDM）的关联还很缺乏。
本研究纳入了 1449 名孕妇，这些孕妇来自中国江苏出生队列（JBC）研究。在妊娠早期采集尿液样本，并测量尿钛浓度和非靶向代谢组学。泊松回归估计妊娠早期的钛暴露与随后发生 GDM 的风险之间的关联。多元线性回归筛选与钛相关的尿代谢物。中介分析评估候选代谢物和途径的中介作用。
按照 tertiles 参数化，钛与 GDM 风险呈正剂量反应关系（趋势 P 值=0.008），与暴露于第一 tertile 水平的女性相比，暴露于最高 tertile 水平的女性 GDM 风险增加 30%（相对风险 [RR] = 1.30 [95%CI：1.06，1.61]）。同时，我们确定了涉及四个氨基酸代谢途径的钛相关代谢物。值得注意的是，氨基酸酰基-tRNA 生物合成和丙氨酸、天冬氨酸和谷氨酸代谢的扰动分别介导了 27.1%和 31.0%的钛暴露对 GDM 的相对效应。具体而言，三种与钛相关的代谢物，胆碱、肌酸和 L-丙氨酸，对钛暴露与 GDM 风险之间的关联表现出主要的中介作用。
在这项前瞻性研究中，我们首次发现妊娠早期钛暴露与 GDM 风险增加之间存在相关性。我们揭示了氨基酸代谢紊乱如何介导钛暴露与 GDM 之间联系的新见解。值得注意的是，胆碱、肌酸和 L-丙氨酸是影响这种关联的关键介质。我们的研究结果表明，妊娠早期钛暴露增加可导致氨基酸代谢紊乱，从而增加 GDM 的风险。
