Mixture effects of trace element levels on cardiovascular diseases and type 2 diabetes risk in adults using G-computation analysis

There is an increasing concern about the health effects of exposure to a mixture of pollutants. This study aimed to evaluate the associations between serum levels of heavy/essential metals ([Arsenic (As), Cadmium (Cd), Mercury (Hg), Lead (Pb), Nickel (Ni), Chromium (Cr), Copper (Cu), Iron (Fe), and Zinc (Zn)]) and the risk of developing cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D). Data were collected from 450 participants (150 with CVDs, 150 with T2D, and 150 healthy subjects) randomly selected from the Ravansar Non-Communicable Disease (RaNCD) cohort in Western Iran, covering the years 2018-2023. Trace element levels in the serum samples were assayed using ICP-MS. Logistic regression was performed to estimate the adjusted risk of exposure to single and multi-metals and CVD/T2D. Odds ratios were adjusted for age, sex, education, residential areas, hypertension, and BMI. The mixture effect of exposure to multi-metals and CVD/T2D was obtained using Quantile G-computation (QGC). In the logistic regression model, chromium, nickel, and zinc levels were associated with CVD, and significant trends were observed for these chemical quartiles (P < 0.001). Arsenic, chromium, and copper levels were also associated with T2D. The weight quartile sum (WQS) index was significantly associated with both CVD (OR 4.17, 95% CI 2.16-7.69) and T2D (OR 11.96, 95% CI 5.65-18.26). Cd, Pb, and Ni were the most heavily weighed chemicals in these models.The Cd had the highest weight among the metals in the CVD model (weighted at 0.78), followed by Hg weighted at 0.197. For T2D, the serum Pb (weighted at 0.32), Ni (weighted at 0.19), Cr (weighted at 0.17), and Cd (weighted at 0.14) were the most weighted in the G-computation model. The results showed the significant role of toxic and essential elements in CVDs and T2D risk. This association may be driven primarily by cadmium and mercury for CVDs and Pb, Ni, Cr, and Cd for T2D, respectively. Prospective studies with higher sample sizes are necessary to confirm or refute our preliminary results as well as to determine other important elements.