The relationship between carotenoids and diabetic nephropathy: insights from NHANES

Diabetic nephropathy (DN) poses significant health risks and imposes a substantial global disease burden. The association between carotenoid intake and DN remains unclear. Utilizing data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES), this study investigates the relationship between multiple carotenoid subtypes and DN, aiming to inform exploratory insights for potential preventive strategies.

This cross-sectional analysis utilized NHANES 2007-2018 data with a multistage stratified sampling design. After a four-stage screening process, baseline participants were selected by excluding individuals with lacking diabetes-related data, pregnant women, and those with incomplete carotenoid intake or DN diagnostic records. Model 1 included 25,483 participants, while Model 2 comprised retained 13,271 participants after further adjustment for covariates (demographic characteristics, lifestyle factors, clinical indicators, and socioeconomic parameters). Dietary intake of six carotenoid subtypes (α-carotene, β-carotene, β-cryptoxanthin, Lycopene, Lutein, Zeaxanthin) was calculated using as the mean of two standardized 24-h dietary recalls. Type 2 diabetes mellitus (T2DM) was diagnosed based on fasting plasma glucose (≥126 mg/dL), HbA1c (≥6.5%), hypoglycemic medication use, or clinical diagnosis. DN was defined as a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² in T2DM patients. Statistical analyses employed weighted multivariable logistic regression using the R survey package, adjusting for sampling design and covariates. Associations were quantified as odds ratios (ORs per 10 μg/d carotenoid intake) with Benjamini-Hochberg correction for multiple comparisons. The significance threshold was set at α = 0.05.

This NHANES-based study revealed nonlinear associations between dietary carotenoids and diabetic nephropathy (DN) risk, with notable gender-and ethnicity-specific gender/ethnicity-specific effects. Univariate analysis demonstrated elevated DN risk with higher β-cryptoxanthin intake (OR = 1.413, 95% CI), though significance was attenuated dissipated after multivariable adjustment, suggesting confounding mediation by obesity and hypertension. Multivariable models identified threshold effects: the low α-carotene intake group exhibited a 75% reduced risk (OR = 0.25, 95% CI), while the high-intake group showed a paradoxical risk elevation (OR = 2.24, 95% CI). β-Carotene displayed gender-divergent effects, with the highest tertile significantly reducing risk in males by 43% (OR = 0.57, 95% CI). Interaction models highlighted intensified α-carotene protection in males and Non-Hispanic White (OR = 0.27-0.29), whereas lycopene correlated with a fivefold increased DN risk in Non-Hispanic Black (OR = 4.99, 95% CI). Cardinal risk factors included advanced age (OR = 1.06/year), obesity (OR = 1.07/BMI unit), male sex (OR = 3.05), and hypertension (OR = 4.7), while higher education (OR = 0.72) and moderate alcohol consumption exerted inversely associated effects. These findings underscore the necessity of integrating nutrient thresholds (e.g., α-carotene optimization) and social determinants into DN prevention, though racial subgroup analyses warrant validation through prospective cohorts due to sample size constraints.

Clinicians managing DN should: Prioritize Consider α-carotene's biphasic dose-response relationship, prioritizing intake within the optimal dosage window; Utilize Leverage β-carotene's gender-specific benefits for male patients; Exercise caution in consider exploringing lycopene-rich dietary interventions diets for African American populations. Public health initiatives should incorporate nutrient-gender-ethnicity triadic assessments into DN education programs to advance precision nutrition guidelines.