Through multiple different pathways, the environmental multiple metals make their ways to the human bodies, where they induce different levels of the oxidative stress response. This study further investigated the impact of multiple-metal exposure on the risk of developing proliferative diabetic retinopathy (PDR). We designed a case-control study with type 2 diabetic patients (T2D), in which the case group was the proliferative diabetic retinopathy group (PDR group), while the control group was the non-diabetic retinopathy group (NDR group). Graphite furnace atomic absorption spectrometry (GFAAS) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to detect the metal levels in our participants' urine samples. The least absolute shrinkage and selection operator (LASSO) regression approach was used to include these representative trace elements in a multiple exposure model. Following that, logistic regression models and Bayesian kernel machine regression (BKMR) models were used to describe the effect of different elements and also analyze their combined effect. In the single-element model, we discovered that lithium (Li), cadmium (Cd), and strontium (Sr) were all positively related to PDR. The multiple-exposure model revealed a positive relationship between Li and PDR risk, with a maximum quartile OR of 2.80 (95% CI: 1.10-7.16). The BKMR model also revealed that selenium (Se) might act as a protective agent, whereas magnesium (Mg), Li, and Cd may raise the risk of PDR. In conclusion, our study not only revealed an association between exposure to multiple metals and PDR risk but it also implied that urine samples might be a useful tool to assess PDR risk.
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