Dietary oxidative balance and renal impairment in diabetes identified by machine learning and functional analysis.

BACKGROUND

Oxidative stress has been implicated in albuminuria-related renal abnormalities in diabetes; however, the combined associations of pro-oxidant and antioxidant dietary components with UACR-defined renal impairment remain unclear. This study aimed to investigate the association between dietary oxidative balance and renal impairment in patients with diabetes and to conduct exploratory in vitro experiments examining whether selected nutrients modulate AKT phosphorylation under high-glucose conditions.

METHODS

Data from diabetic participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2020 were analyzed. Based on the conceptual framework of the oxidative balance score (OBS), a panel of oxidative balance-related dietary components, including antioxidant and pro-oxidant factors, was selected for analysis. Multiple machine learning models were applied to assess associations between these dietary factors and renal impairment assessed by UACR, with model interpretability analyses identifying key contributors. In vitro experiments were conducted to explore whether selected nutrients modulated AKT phosphorylation under high-glucose conditions.

RESULTS

A total of 9,764 participants with diabetes were included. Among all models, the random forest algorithm achieved the best predictive performance. Feature importance analysis identified vitamin E, β-carotene, and magnesium as the most influential dietary factors associated with renal impairment in diabetes. In HK-2 cells, these nutrients partially restored AKT phosphorylation that was suppressed by high-glucose conditions, suggesting possible pathway-level relevance under high-glucose conditions.

CONCLUSION

This study identified significant associations between oxidative balance-related dietary components and renal impairment in diabetes and highlighted vitamin E, β-carotene, and magnesium as key antioxidant-related dietary factors. Exploratory in vitro findings suggest that these nutrients may modulate high-glucose-induced AKT signaling suppression, warranting further investigation in future observational and mechanistic studies.