Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain; Instituto de Investigación Biosanitaria (ibs.GRANADA). Avda. de Madrid, 15. Pabellón de Consultas Externas 2, 2(a) Planta, 18012, Granada, Spain.
Universidad de Granada. Department of Preventive Medicine and Public Health, Pharmacy School. Campus de Cartuja S/n, 18071, Granada, Spain.
Environ Pollut. 2024 Jan 1;340(Pt 1):122714. doi: 10.1016/j.envpol.2023.122714. Epub 2023 Oct 14.
Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease, i.e. obesity, insulin resistance, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-c) levels and arterial hypertension. Phthalates are environmental chemicals which might influence the risk of the aforementioned disturbances, although the evidence is still controversial. The objective of this work was to synthesize the evidence on the association between human phthalate exposure and metabolic syndrome or any of its components. In this systematic review, the PRISMA guidelines were followed and the literature was search in PubMed, Web of Science and Scopus. Longitudinal and cross-sectional studies were included, the later only if a subclinical marker of disease was evaluated. The methodological quality was assessed with the Newcastle Ottawa Scale and a checklist for Analytical Cross-Sectional Studies developed in the Joanna Briggs Institute. A total of 58 articles were identified that showed high heterogenicity in the specific phthalates assessed, time-window of exposure and duration of follow-up. The quality of the studies was evaluated as high (n = 46, score >7 points) or medium (n = 12, score 4-6). The most frequently studied phthalates were DEHP-MEHP, MBzP and MEP. The evidence revealed a positive association between prenatal (in utero) exposure to most phthalates and markers of obesity in the offspring, but contradictory results when postnatal exposure and obesity were assessed. Moreover, postnatal phthalate exposure showed positive and very consistent associations with markers of diabetes and, to a lesser extent, with triglyceride levels. However, fewer evidence and contradictory results were found for HDL-c levels and markers of hypertension. The suggested mechanisms for these metabolic effects include transcription factor PPAR activation, antagonism of thyroid hormone function, antiandrogenic effects, oxidative stress and inflammation, and epigenetic changes. Nevertheless, as the inconsistency of some results could be related to differences in the study design, future research should aim to standardise the exposure assessment.
代谢综合征是一组会增加心血管疾病风险的病症，包括肥胖、胰岛素抵抗、高三酰甘油血症、低高密度脂蛋白胆固醇（HDL-c）水平和动脉高血压。邻苯二甲酸酯是一种环境化学物质，可能会影响上述紊乱的风险，尽管证据仍存在争议。这项工作的目的是综合评估人类邻苯二甲酸酯暴露与代谢综合征或其任何组成部分之间的关联。在这项系统评价中，遵循了 PRISMA 指南，并在 PubMed、Web of Science 和 Scopus 中搜索了文献。纳入了纵向和横断面研究，后者仅在评估疾病的亚临床标志物时才纳入。使用纽卡斯尔-渥太华量表和 Joanna Briggs 研究所制定的分析性横断面研究检查表评估了方法学质量。共确定了 58 篇文章，这些文章在所评估的特定邻苯二甲酸酯、暴露时间窗口和随访时间方面表现出高度异质性。研究质量评估为高（n=46，评分>7 分）或中（n=12，评分 4-6 分）。研究中最常研究的邻苯二甲酸酯是 DEHP-MEHP、MBzP 和 MEP。证据表明，大多数邻苯二甲酸酯在产前（宫内）暴露与后代肥胖标志物之间存在正相关，但在评估产后暴露与肥胖时则得出相互矛盾的结果。此外，产后邻苯二甲酸酯暴露与糖尿病标志物呈正相关且非常一致，而与甘油三酯水平的相关性则较小。然而，关于 HDL-c 水平和高血压标志物的证据较少且相互矛盾。这些代谢效应的推测机制包括转录因子 PPAR 激活、甲状腺激素功能拮抗、抗雄激素作用、氧化应激和炎症以及表观遗传变化。然而，由于一些结果的不一致性可能与研究设计的差异有关，因此未来的研究应旨在标准化暴露评估。
