Association of Cumulative Exposure to Heavy Metal Mixtures with Obesity and Its Comorbidities among U.S. Adults in NHANES 2003-2014

摘要

Background: Some heavy metals have been associated with obesity and obesity comorbidities. The associations have typically been examined for individual metals. Objectives: We update our Environmental Risk Score (ERS), a summary measure to examine the risk of exposure to multi-pollutants in epidemiologic research, to evaluate the associations of cumulative exposure to a mixture of correlated heavy metals with obesity and its comorbidities including hypertension (HTN), and type-2 diabetes mellitus (T2DM) while accounting for high degree correlations and potential interactions among metal mixtures components. Methods: We examined blood and urinary measurements of 18 heavy metals among 9,537 adults in NHANES 2003-2014. We randomly split data into a training set for the construction of ERS (n=6,675) and a testing set for validation (n=2,862). ERS of heavy metal mixtures were computed for obesity using adaptive elastic-net (AENET) with 189 predictors including 18 main effects, 18 square terms, and 153 pairwise interactions of heavy metals. Regression analyses with complex survey designs were performed to assess the association of ERS with obesity and its comorbidities. Results: 8 main effects (BPb, BCd, BHg, UDMA, UMMA, UBa, UHg and UTI), 3 square terms (BCd, UCd and USb), and 7 pairwise interactions (BPb&UCd, BPb&UMMA, BPb&UU, UCd&UMMA, UDMA&UW, UPb&USb and UMMA&UCo) of heavy metals have been selected by AENET for construction of ERS of obesity-related heavy metal mixtures. The ERS was positively associated with waist circumference, body mass index, skinfold thickness and total body fat, independent of age, sex, race/ethnicity, education, smoking, physical activity and NHANES cycle (Ps < 0.05). Positive associations of ERS with both HTN and T2DM have also been observed (Ps < 0.05). Conclusions: Our study suggests the potential role of exposure to heavy metals mixtures as a contributing factor to obesity and its related chronic conditions such as hypertension and T2DM.