Cadmium Exposure in Young Adulthood Is Associated with Risk of Nonalcoholic Fatty Liver Disease in Midlife

Background: Studies have suggested that cadmium (Cd) may be involved in the etiology of nonalcoholic fatty liver disease (NAFLD), but available data in human is sparse. Aims: We aimed to examine Cd exposure in young adulthood in relation to prevalent NAFLD in midlife among American adults. Methods: This study included 2446 participants from the Coronary Artery Risk Development in Young Adults study with toenail Cd measurement at exam year 2 (baseline) and computed tomography quantification of liver fat at exam year 25. Toenail Cd concentrations were considered as a reliable marker of long-term exposure. NAFLD was defined if liver attenuation < 51 Hounsfield units after excluding other possible causes of liver fat. Multivariable-adjusted logistic regression models were used to estimate the odds ratio of NAFLD by Cd exposure. Results: Median toenail Cd concentration was 8.2 ppb (inter-quartile range 4.3–18.6 ppb). After 23 years from baseline, 580 participants with prevalent NAFLD (24% prevalence) in midlife were identified. Compared with individuals in the lowest quartile, those in the highest quartile of toenail Cd had a significantly higher odds of NAFLD (OR: 1.43, 95% CI: 1.02, 1.99, P for trend: 0.04) after adjustment for demographics, socioeconomics, major lifestyle factors, and baseline levels of body mass index, lipids, and fasting insulin. The association was not significantly modified by race, sex, BMI, or smoking status at baseline. Conclusions: Toenail Cd concentration was associated with a higher odds of prevalent NAFLD23 years later in life in this cohort of US general population.