Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W168th Street, New York, NY, 10032, USA.
Curr Diab Rep. 2019 Nov 22;19(12):147. doi: 10.1007/s11892-019-1272-9.
In utero influences, including nutrition and environmental chemicals, may induce long-term metabolic changes and increase diabetes risk in adulthood. This review evaluates the experimental and epidemiological evidence on the association of early-life arsenic exposure on diabetes and diabetes-related outcomes, as well as the influence of maternal nutritional status on arsenic-related metabolic effects.
Five studies in rodents have evaluated the role of in utero arsenic exposure with diabetes in the offspring. In four of the studies, elevated post-natal fasting glucose was observed when comparing in utero arsenic exposure with no exposure. Rodent offspring exposed to arsenic in utero also showed elevated insulin resistance in the 4 studies evaluating it as well as microRNA changes related to glycemic control in 2 studies. Birth cohorts of arsenic-exposed pregnant mothers in New Hampshire, Mexico, and Taiwan have shown that increased prenatal arsenic exposure is related to altered cord blood gene expression, microRNA, and DNA methylation profiles in diabetes-related pathways. Thus far, no epidemiologic studies have evaluated early-life arsenic exposure with diabetes risk. Supplementation trials have shown B vitamins can reduce blood arsenic levels in highly exposed, undernourished populations. Animal evidence supports that adequate B vitamin status can rescue early-life arsenic-induced diabetes risk, although human data is lacking. Experimental animal studies and human evidence on the association of in utero arsenic exposure with alterations in gene expression pathways related to diabetes in newborns, support the potential role of early-life arsenic exposure in diabetes development, possibly through increased insulin resistance. Given pervasive arsenic exposure and the challenges to eliminate arsenic from the environment, research is needed to evaluate prevention interventions, including the possibility of low-cost, low-risk nutritional interventions that can modify arsenic-related disease risk.
目的综述：子宫内的影响因素，包括营养和环境化学物质，可能导致长期代谢变化，并增加成年后患糖尿病的风险。这篇综述评估了早期砷暴露与糖尿病及相关结局之间的关系的实验和流行病学证据，以及母体营养状况对砷相关代谢影响的影响。
最新发现：已有 5 项关于啮齿动物的研究评估了子宫内砷暴露与后代糖尿病之间的关系。在其中 4 项研究中，与无暴露相比，子宫内砷暴露的后代在出生后会出现空腹血糖升高。在 4 项评估胰岛素抵抗的研究中，暴露于子宫内砷的啮齿动物后代也表现出胰岛素抵抗，在 2 项研究中还观察到与血糖控制相关的 microRNA 变化。新罕布什尔州、墨西哥和台湾的砷暴露孕妇出生队列研究表明，产前砷暴露增加与糖尿病相关途径的脐带血基因表达、microRNA 和 DNA 甲基化谱的改变有关。迄今为止，没有流行病学研究评估早期砷暴露与糖尿病风险之间的关系。补充试验表明，B 族维生素可以降低高度暴露、营养不足人群的血液砷水平。动物证据支持充足的 B 族维生素状态可以降低早期生活中砷引起的糖尿病风险，尽管缺乏人类数据。动物实验研究和人类证据表明，子宫内砷暴露与新生儿与糖尿病相关的基因表达途径的改变有关，这支持了早期砷暴露在糖尿病发展中的潜在作用，可能是通过增加胰岛素抵抗。鉴于普遍存在的砷暴露以及从环境中消除砷的挑战，需要进行研究以评估预防干预措施，包括可能的低成本、低风险的营养干预措施，这些干预措施可以改变与砷相关的疾病风险。
