Arsenic exposure is associated with obesity- or excess adiposity-related disorders, including cardiometabolic diseases. Previously, many human studies attempted to establish the association of arsenic exposure with obesity, mainly through body mass index (BMI) but failed to provide any concrete evidence. Our study aimed to investigate the arsenic-related adiposity and its relationship with cardiometabolic diseases. Of the 524 participants, 126 and 398, respectively, were chosen from low- and high-arsenic exposure areas in Bangladesh. Obesity or body fat (adiposity) of the participants was measured by anthropometric measures [BMI, waist circumference (WC), and triceps skinfold thickness (TSFT)] and a serum biomarker, leptin. Sarcopenic characteristics were assessed by lean body mass (LBM) and serum creatinine levels. Insulin resistance, as measured by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), hypertension, and hyperglycemia, were considered as the risk factors for cardiometabolic diseases. There were significant positive associations between drinking water, hair, and nail arsenic concentrations and the levels of WC and TSFT after adjusting for potential confounders. However, there were no significant associations with BMI. Increased arsenic exposure levels were associated with increased leptin levels [(Regression coefficient (β) = 1.00, 95% confidence interval (CI): 0.53, 1.46) for water, (β = 1.44, 95% CI: 0.42, 2.46) for hair, and (β = 1.47, 95% CI: 0.32, 2.61) for nail arsenic]. Notably, leptin levels had inverse associations with LBM (β = -7.87, 95% CI: -13.30, -2.45) and creatinine levels (β = -15.65, 95% CI: -21.50, -9.81). Furthermore, the elevated leptin levels associated with arsenic exposure were connected to higher HOMA-IR levels (β = 0.19, 95% CI: 0.14, 0.24), higher odds of hypertension [Odds ratio (OR) = 1.31, 95% CI: 1.12, 1.53], and hyperglycemia (OR = 1.30, 95% CI: 1.13, 1.47). Taken together, the results of this study demonstrated a unique association between arsenic exposure and adiposity, which could promote arsenic-induced cardiometabolic disorders by mirroring the distinctive characteristics of age-associated sarcopenic obesity.

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