{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:40:06Z","timestamp":1770046806723,"version":"3.49.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetes mellitus is a leading cause of end-stage renal disease (ESRD), with up to 35% of patients with diabetes mellitus developing kidney disease. This study aims to monitor protein expression changes in ESRD patients with and without type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 186 ESRD patients who underwent arteriovenous fistula creation surgery were enrolled in this study. Of these, 148 patients were classified into the T2DM (n = 73) and non-T2DM (n = 75) groups. Data-independent acquisition proteomic analysis was conducted to analyze differentially expressed proteins. Enzyme-linked immunosorbent assay kits, immunohistochemical staining, Western blotting were employed to validate the differently expressed proteins within the cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Proteomic analysis identified 26 upregulated and 15 downregulated proteins in the T2DM group compared with the non-T2DM group. The serum concentrations of 4-hydroxynonenal, malondialdehyde, and glutathione were elevated in the T2DM group. The immunohistochemical staining index for GPX4 and xCT was lower, while \u03b1-SMA, IL-6, TNF-\u03b1, and TGF-\u03b2 levels were higher in the T2DM group compared with the non-T2DM group. Western blotting indicated the downregulation of SOD1 and GPX4 as well as upregulation of PTGS2 and ACLS4 in the T2DM group accompanied by increased levels of Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , total iron, and Fe\n                      <jats:sup>3+<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study underscores oxidoreductase activity-related proteins, including ferroptosis-related proteins to be differentially expressed in ESRD combined with T2DM.<\/jats:p>\n                  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