{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T15:55:40Z","timestamp":1781884540835,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments examining whether selected nutrients modulate AKT phosphorylation under high-glucose conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from diabetic participants in the National Health and Nutrition Examination Survey (NHANES) 1999\u20132020 were analyzed. Based on the conceptual framework of the oxidative balance score (OBS), a panel of oxidative balance\u2013related 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.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments were conducted to explore whether selected nutrients modulated AKT phosphorylation under high-glucose conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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, \u03b2-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified significant associations between oxidative balance-related dietary components and renal impairment in diabetes and highlighted vitamin E, \u03b2-carotene, and magnesium as key antioxidant-related dietary factors. Exploratory\n                      <jats:italic>in vitro<\/jats:italic>\n                      findings suggest that these nutrients may modulate high-glucose\u2013induced AKT signaling suppression, warranting further investigation in future observational and mechanistic studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1792300","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:25:10Z","timestamp":1777868710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dietary oxidative balance and renal impairment in diabetes identified by machine learning and functional analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Renjie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xincan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luheng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zicheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.4239\/wjd.v10.i5.269","article-title":"Evolving spectrum of diabetic nephropathy","volume":"10","author":"Kopel","year":"2019","journal-title":"World J Diabetes"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1900\/RDS.2021.17.1","article-title":"Molecular mechanisms involved in Intrarenal renin-angiotensin and alternative pathways in diabetic nephropathy \u2013 a review","volume":"17","author":"Bahreini","year":"2021","journal-title":"Rev Diabet Stud"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.3390\/biomedicines10071644","article-title":"Metformin is associated with the inhibition of renal artery AT1R\/ET-1\/iNOS Axis in a rat model of diabetic nephropathy with suppression of inflammation and oxidative stress and kidney injury","volume":"10","author":"Dawood","year":"2022","journal-title":"Biomedicine"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1297484","DOI":"10.3389\/fimmu.2023.1297484","article-title":"Immune and oxidative stress disorder in ovulation-dysfunction women revealed by single-cell transcriptome","volume":"14","author":"Qi","year":"2023","journal-title":"Front Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1185317","DOI":"10.3389\/fimmu.2023.1185317","article-title":"Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols","volume":"14","author":"Jin","year":"2023","journal-title":"Front Immunol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/nri.2017.66","article-title":"Mitochondrial control of immunity: beyond ATP","volume":"17","author":"Mehta","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"300","DOI":"10.3390\/antiox11020300","article-title":"Oxidative balance scores (OBSs) integrating nutrient, food and lifestyle dimensions: development of the NutrientL-OBS and FoodL-OBS","volume":"11","author":"Hern\u00e1ndez-Ruiz","year":"2022","journal-title":"Antioxidants"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"108354","DOI":"10.1016\/j.jdiacomp.2022.108354","article-title":"Inflammation level in type 2 diabetes is associated with dietary advanced glycation end products, Mediterranean diet adherence and oxidative balance score: a pathway analysis","volume":"37","author":"Demirer","year":"2023","journal-title":"J Diabetes Complicat"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.3390\/medicina56090455","article-title":"Comparison of conventional statistical methods with machine learning in medicine: diagnosis, drug development, and treatment","volume":"56","author":"Rajula","year":"2020","journal-title":"Medicina"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e262","DOI":"10.1016\/s1470-2045(19)30149-4","article-title":"Big data and machine learning algorithms for health-care delivery","volume":"20","author":"Ngiam","year":"2019","journal-title":"Lancet Oncol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1097\/JU.0000000000001005","article-title":"The urine albumin-to-creatinine ratio and kidney function after nephrectomy","volume":"204","author":"Sun","year":"2020","journal-title":"J Urol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41580-021-00407-0","article-title":"A guide to machine learning for biologists","volume":"23","author":"Greener","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1412823","DOI":"10.3389\/fendo.2024.1412823","article-title":"Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study","volume":"15","author":"Liu","year":"2024","journal-title":"Front Endocrinol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/jdi.14390","article-title":"Oxidative balance is associated with diabetic kidney disease and mortality in adults with diabetes mellitus: insights from NHANES database and Mendelian randomization","volume":"16","author":"Jiang","year":"2025","journal-title":"J Diabetes Investig"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1499044","DOI":"10.3389\/fnut.2024.1499044","article-title":"Oxidative balance score is associated with the risk of diabetic kidney disease in patients with type 2 diabetes mellitus: evidence from NHANES 2007-2018","volume":"11","author":"Liang","year":"2024","journal-title":"Front Nutr"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"308","DOI":"10.2741\/2066","article-title":"Magnesium homeostasis in mammalian cells","volume":"12","author":"Romani","year":"2007","journal-title":"Front Biosci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1146\/annurev-nutr-071811-150656","article-title":"Hypomagnesemia and inflammation: clinical and basic aspects","volume":"32","author":"Weglicki","year":"2012","journal-title":"Annu Rev Nutr"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1258\/002367790780890086","article-title":"Diet-induced nephrocalcinosis and urinary excretion of albumin in female rats","volume":"24","author":"Van Camp","year":"1990","journal-title":"Lab Anim"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3390\/nu8040217","article-title":"Micronutrient intakes and incidence of chronic kidney disease in adults: Tehran lipid and glucose study","volume":"8","author":"Farhadnejad","year":"2016","journal-title":"Nutrients"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"8199","DOI":"10.3390\/nu7095388","article-title":"Magnesium in prevention and therapy","volume":"7","author":"Gr\u00f6ber","year":"2015","journal-title":"Nutrients"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1111\/dme.12250","article-title":"Magnesium intake decreases type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama study","volume":"30","author":"Hata","year":"2013","journal-title":"Diabet Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e57720","DOI":"10.1371\/journal.pone.0057720","article-title":"Magnesium and the risk of cardiovascular events: a meta-analysis of prospective cohort studies","volume":"8","author":"Qu","year":"2013","journal-title":"PLoS One"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1136\/jim-2018-000966","article-title":"Low serum magnesium is associated with faster decline in kidney function: the Dallas heart study experience","volume":"67","author":"Ferr\u00e8","year":"2019","journal-title":"J Investig Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.2337\/dc12-0226","article-title":"Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease","volume":"35","author":"Sakaguchi","year":"2012","journal-title":"Diabetes Care"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1159\/000450861","article-title":"Dietary magnesium and kidney function decline: the healthy aging in neighborhoods of diversity across the life span study","volume":"44","author":"Rebholz","year":"2016","journal-title":"Am J Nephrol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2147\/VHRM.S242685","article-title":"Vascular calcification: an important understanding in nephrology","volume":"16","author":"Zununi Vahed","year":"2020","journal-title":"Vasc Health Risk Manag"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1080\/0886022X.2020.1758722","article-title":"Genome-wide identification of lncRNAs and mRNAs differentially expressed in human vascular smooth muscle cells stimulated by high phosphorus","volume":"42","author":"Bao","year":"2020","journal-title":"Ren Fail"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s13340-020-00483-1","article-title":"Retrospective study of factors associated with progression and remission\/regression of diabetic kidney disease-hypomagnesemia was associated with progression and elevated serum alanine aminotransferase levels were associated with remission or regression","volume":"12","author":"Yanagawa","year":"2021","journal-title":"Diabetol Int"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.dsx.2018.03.013","article-title":"The effect of vitamin C and\/or E supplementations on type 2 diabetic adult males under metformin treatment: a single-blinded randomized controlled clinical trial","volume":"12","author":"El-Aal","year":"2018","journal-title":"Diabetes Metab Syndr"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e95008","DOI":"10.1371\/journal.pone.0095008","article-title":"Influence of vitamin E supplementation on glycaemic control: a meta-analysis of randomised controlled trials","volume":"9","author":"Xu","year":"2014","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e0178699","DOI":"10.1371\/journal.pone.0178699","article-title":"Antioxidant agents for delaying diabetic kidney disease progression: a systematic review and meta-analysis","volume":"12","author":"Bolignano","year":"2017","journal-title":"PLoS One"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1681\/asn.2010010010","article-title":"Pathologic classification of diabetic nephropathy","volume":"21","author":"Tervaert","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1177\/1535370216661780","article-title":"\u0393-Carboxyethyl hydroxychroman, a metabolite of \u03b3-tocopherol, preserves nitric oxide bioavailability in endothelial cells challenged with high glucose","volume":"241","author":"Li","year":"2016","journal-title":"Exp Biol Med (Maywood)"},{"key":"ref34","volume-title":"Vitamin E Induces Regular Structure and Stability of Human Insulin, More Intense Than Vitamin D3 \u2013 PubMed","author":"Soleymani","year":""},{"key":"ref35","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1046\/j.0742-3071.2001.00574.x","article-title":"Double-blind, randomised study of the effect of combined treatment with vitamin C and E on albuminuria in type 2 diabetic patients","volume":"18","author":"Gaede","year":"2001","journal-title":"Diabet Med"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"S194","DOI":"10.1002\/mnfr.200800053","article-title":"Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans","volume":"53","author":"Maiani Maiani","year":"2009","journal-title":"Mol Nutr Food Res"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.plipres.2018.04.004","article-title":"A global perspective on carotenoids: metabolism, biotechnology, and benefits for nutrition and health","volume":"70","author":"Rodriguez-Concepcion","year":"2018","journal-title":"Prog Lipid Res"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1053\/j.jrn.2018.05.008","article-title":"The association of serum carotenoids, tocopherols, and ascorbic acid with rapid kidney function decline: the coronary artery risk development in young adults (CARDIA) study","volume":"29","author":"Hirahatake","year":"2019","journal-title":"J Ren Nutr"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.2337\/dc21-2371","article-title":"Associations of serum carotenoids with risk of cardiovascular mortality among individuals with type 2 diabetes: results from NHANES","volume":"45","author":"Qiu","year":"2022","journal-title":"Diabetes Care"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3390\/medsci7040056","article-title":"Magnesium: the forgotten electrolyte-a review on hypomagnesemia","volume":"7","author":"Ahmed","year":"2019","journal-title":"Med Sci Basel"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/ki.2014.331","article-title":"Results from the atherosclerosis risk in communities study suggest that low serum magnesium is associated with incident kidney disease","volume":"87","author":"Tin","year":"2015","journal-title":"Kidney Int"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"429","DOI":"10.5414\/cnp63429","article-title":"Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2","volume":"63","author":"Pham","year":"2005","journal-title":"Clin Nephrol"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1792300\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T15:19:13Z","timestamp":1781882353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1792300\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,4]]},"references-count":42,"alternative-id":["10.3389\/fnut.2026.1792300"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1792300","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,4]]},"article-number":"1792300"}}