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Metals, as common pollutants, are ubiquitously distributed throughout the ecosystem and have attached much attention due to their high toxicity, degradation-resistant and strong persistence. A growing number of studies reported that multiple metals were related to a higher risk of cardiovascular metabolic diseases, including obesity and diabetes (Velmurugan et al., 2018; Xu et al., 2022; Qu et al., 2023). Unlike adults, children might face a greater threat from metals exposure due to its their hand-to-mouth behavior and vulnerable system. However, prior studies mostly focused on the effect of metal exposure on childhood obesity (Zeng et al., 2019; Zhou et al., 2020; Signes-Pastor et al., 2021). The evidence available on the association of metals and fasting blood glucose (FBG) in children was quite limited.

Several cross-sectional studies explored the effects of a single metal or few heavy metals on FBG, but no consistent conclusion was reached. A US study conducted in children and adolescents aged 6–19 years found that serum copper (Cu) was associated with increased FBG, fasting insulin and glycohemoglobin (Zang et al., 2018). Another study observed the significant effect of serum magnesium, but not Cu, chromium (Cr), or selenium (Se) on reduced FBG in Iranian adolescents (Kelishadi et al., 2015). However, several studies didn’t show any significant links of blood lead (Pb) (Xu et al., 2017), mercury (Zhang et al., 2018), and cadmium (Cd) (Kelishadi et al., 2013) with FBG in children and adolescents. Also, no evidence was covered on the effects of other essential metals, such as zinc (Zn), manganese (Mn) and non-essential metals, antimony (Sb), thallium (Tl) on children’s FBG. More importantly, multiple metals usually coexisted in children, but no study considered the effect of metals mixture on FBG in children. Accordingly, all of the aforementioned studies mainly focused on common heavy metals, but ignored the relations of essential metals and other non-essential metals with FBG in children.

Furthermore, it should be noted what effective measures are warranted to take to protect children from the harmful effects of metals. A previous study reported that physical activity could improve insulin sensitivity in children (Huus et al., 2016). A cross-sectional study found that regular physical activity could attenuate the impact of Cd on the risk of cardiovascular disease in US adults (Kong et al., 2023). Nevertheless, it’s unknown whether physical activity could modify the relationships between multiple metals and FBG in children.

Environmental metals that enter the human body accumulate partly in organs and tissues, and are mainly excreted through kidneys (Peter and Viraraghavan, 2005; Jarup and Akesson, 2009; Ye et al., 2018; Palma-Lara et al., 2020). That is, urinary metals might be a better indicator to reflect internal exposure level for most metals, with the exception of elements such as Pb and Mn, and obtaining multiple repeated samples could increase the reliability of the results. Therefore, we conducted 2 longitudinal panel studies across 3 seasons to assess the associations of continuous 4-day morning urinary essential and non-essential metals, as individual or mixture, with FBG and the modification of extra-school activity among healthy children.



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