Inverse association between circulating carotenoids and type 2 diabetes in adults: a mediation analysis of serum biomarkers and anthropometric parameters

Given inconsistent evidence on the inverse link between serum carotenoids and type 2 diabetes (T2D) risk, this study investigated these associations and potential mediating pathways using nationally representative longitudinal data. We analyzed 7601 non-pregnant adults (≥20 years) from NHANES 2001–2018, examining six serum carotenoids, eight biomarkers, two anthropometric measures, and T2D history. Restricted cubic spline analysis revealed significant non-linear inverse associations between total serum carotenoids, α-carotene, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin concentrations and the risk of T2D. Following multivariable adjustment, quartile-based analyses demonstrated that higher concentrations of total serum carotenoids and most individual carotenoids were significantly inversely associated with T2D risk, relative to the lowest quartile. Mediation analysis showed that 9 of 10 markers significantly mediated these associations, with effects ranging from 3.94% (C-reactive protein) to 45.81% (fasting glucose). These findings support a protective role of carotenoids against T2D and highlight the mediating roles of serum biomarkers and anthropometric parameters.