Clustering environmental pollutants associated with increased risk of metabolic disease: a hierarchical analysis

Metabolic syndrome (MetS), which affects one-third of the population of the United States, is a risk factor for chronic diseases such as cardiovascular diseases, stroke, and type 2 diabetes mellitus. Heavy metals (HM) and volatile organic compounds (VOC) are environmental factors typically occurring as mixtures. Although exposures to these substances have been studied separately, the impact of combined HM and VOC exposure on humans and their subsequent risk of developing MetS has not been explored. This study investigates whether combined exposure to HMs and VOCs affects the risk of developing MetS.

The National Health and Nutrition Examination Survey database from 2011 to 2020 was used to determine exposure to HMs and VOCs detected in urine samples from individuals with MetS. Multiple Chi-squared and t-tests were performed to identify variables significantly associated with MetS. Logistic regression analysis was performed on unmatched and age-matched 1:1 case-control data to evaluate whether an association exists among HMs, VOCs, and demographic factors and MetS. A hierarchical cluster analysis was performed to identify combinations of HMs and VOCs linked with an increased risk of MetS.

Logistic regression analysis on unmatched and matched data showed that increasing age and female sex were significantly associated (p < 0.05) with MetS. Among the HMs and VOCs, only N-acetyl-S-(2-cyanoethyl)-l-cysteine and N-acetyl-S-(2-hydroxyethyl)-l-cysteine were found to be significantly associated with MetS. Cluster analysis showed that Cluster 3 was significantly associated with MetS (p < 0.05; OR = 1.49), suggesting that exposure to barium, cadmium, cesium, lead, and VOCs may increase the risk of MetS. After adjusting for covariates, none of the clusters showed a significant association (p > 0.05). In contrast, age (OR = 1.07) and monthly poverty level index ≤ 1.3 (OR = 1.16) were significantly associated with MetS (p < 0.05).

This study revealed that age, lower socioeconomic status, and multiple exposures to combined HM and VOC may have a greater impact with an increased risk of MetS. Cluster analysis highlighted the potential combination of the exposures linked to MetS and the likelihood that demographic factors affect MetS more than exposure to HMs and VOCs. However, further research is needed.

The online version contains supplementary material available at 10.1007/s13755-025-00375-1.