What question did this study set out to answer?

To explore the association between dietary oxidative balance and renal impairment in diabetes and assess nutrient effects on AKT phosphorylation.

May 8, 2026Open Access

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

Key Points

To explore the association between dietary oxidative balance and renal impairment in diabetes and assess nutrient effects on AKT phosphorylation.
Analyzed data from 9,764 diabetic participants in NHANES 1999–2020.
Applied multiple machine learning models to evaluate dietary factors influencing renal impairment using UACR.
Conducted in vitro experiments on HK-2 cells to assess nutrient modulation of AKT phosphorylation.
Random forest algorithm showed the best predictive performance for dietary factors and renal impairment.
Vitamin E, β-carotene, and magnesium were identified as significant dietary contributors to renal impairment.
Nutrients partially restored AKT phosphorylation suppressed by high glucose, indicating potential pathway relevance.

Abstract

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.

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