Journals / Journal of Health Sciences and Medicine / 2026 / Volume: 9 Issue: 6

Serum arginase and nitric oxide levels in type 2 diabetes with and without diabetic nephropathy: associations and diagnostic performance

Selman Gencer(Aksaray Eğitim ve Araştırma Hastanesi)0000-0003-3936-4146
Hasan Şimşek(AKSARAY UNIVERSITY, SCHOOL OF MEDICINE)0000-0001-5573-4923
Pages
—
Publication Date
2026-10-25
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion: Serum arginase may be modestly associated with DN, but neither arginase nor NO appears suitable as a stand-alone diagnostic biomarker.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Aims: This study aimed to compare serum arginase and nitric oxide (NO) levels in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy (DN), evaluate their associations with renal function, and assess their diagnostic performance for DN.
📊
Key Findings & Data:Methods: This retrospective case-control study included 89 patients with T2DM, comprising 45 patients with DN and 44 without nephropathy.
💡
Conclusion & Impact:Conclusion: Serum arginase may be modestly associated with DN, but neither arginase nor NO appears suitable as a stand-alone diagnostic biomarker.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Diabetic nephropathy · arginase · nitric oxide

Abstract

Aims: This study aimed to compare serum arginase and nitric oxide (NO) levels in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy (DN), evaluate their associations with renal function, and assess their diagnostic performance for DN. Methods: This retrospective case-control study included 89 patients with T2DM, comprising 45 patients with DN and 44 without nephropathy. Serum arginase and NO concentrations were measured using ELISA. Group comparisons were performed according to data distribution, and Benjamini-Hochberg false discovery rate correction was applied to secondary laboratory variables. Associations with creatinine, eGFR, and microalbuminuria were evaluated using age- and gender-adjusted partial Spearman correlations. Multivariable linear and logistic regression analyses were performed, and diagnostic performance was assessed using receiver operating characteristic analysis. Results: Serum arginase levels were higher in patients with DN than in those without nephropathy (49.92±14.28 vs. 43.67±12.35 pg/ml; p=0.030), whereas NO levels did not differ significantly [0.757 (0.670-0.952) vs. 0.741 (0.584-0.906) µmol/L; p=0.433]. After adjustment for age and gender, the between-group difference in arginase was attenuated (β=6.25, 95% CI: -0.13-12.64; p=0.055). Arginase remained modestly associated with DN in logistic regression (OR=1.049, 95% CI: 1.002-1.098; p=0.040). Neither biomarker showed significant adjusted correlations with renal parameters. Diagnostic discrimination was limited for arginase (AUC=0.610) and NO (AUC=0.548). Conclusion: Serum arginase may be modestly associated with DN, but neither arginase nor NO appears suitable as a stand-alone diagnostic biomarker.

🔖

Cite This Article

Gencer, S., Şimşek, H. (2026). Serum arginase and nitric oxide levels in type 2 diabetes with and without diabetic nephropathy: associations and diagnostic performance. Journal of Health Sciences and Medicine, Volume: 9 Issue: 6. https://ajindex.com/articles/1668034

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (29)

  1. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. doi:10.1016/j.diabres.2021.109119
  2. Naaman SC, Bakris GL. Diabetic nephropathy: update on pillars of therapy slowing progression. Diabetes Care. 2023;46(9):1574-1586. doi:10.2337/dci23-0030
  3. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12(12):2032-2045. doi:10.2215/CJN.11491116
  4. Ren Y, Li Z, Li W, et al. Arginase: biological and therapeutic implications in diabetes mellitus and its complications. Oxid Med Cell Longev. 2022;2022:2419412. doi:10.1155/2022/2419412
  5. Daehn IS, Ekperikpe US, Stadler K. Redox regulation in diabetic kidney disease. Am J Physiol Renal Physiol. 2023;325(2):F135-F149. doi:10.1152/ajprenal.00047.2023
  6. Janaszak-Jasiecka A, Płoska A, Wierońska J, Dobrucki LW, Kalinowski L. Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets. Cell Mol Biol Lett. 2023; 28(1):21. doi:10.1186/s11658-023-00423-2
  7. Janaszak-Jasiecka A, Siekierzycka A, Płoska A, Dobrucki LW, Kalinowski L. Endothelial dysfunction driven by hypoxia-the influence of oxygen deficiency on NO bioavailability. Biomolecules. 2021;11(7):982. doi:10.3390/biom11070982
  8. Shatanawi A, Momani MS, Al-Aqtash R, Hamdan MH, Gharaibeh MN. L-Citrulline supplementation increases plasma nitric oxide levels and reduces arginase activity in patients with type 2 diabetes. Front Pharmacol. 2020;11:584669. doi:10.3389/fphar.2020.584669
  9. Morris SM Jr, Gao T, Cooper TK, Kepka-Lenhart D, Awad AS. Arginase-2 mediates diabetic renal injury. Diabetes. 2011;60(11):3015-3022. doi:10.2337/db11-0901
  10. You H, Gao T, Cooper TK, Morris SM Jr, Awad AS. Arginase inhibition mediates renal tissue protection in diabetic nephropathy by a nitric oxide synthase 3-dependent mechanism. Kidney Int. 2013;84(6):1189-1197. doi:10.1038/ki.2013.215
  11. Morris SM Jr, You H, Gao T, Vacher J, Cooper TK, Awad AS. Distinct roles of arginases 1 and 2 in diabetic nephropathy. Am J Physiol Renal Physiol. 2017;313(4):F899-F905. doi:10.1152/ajprenal.00158.2017
  12. Zhuge Z, McCann Haworth S, Nihlén C, et al. Red blood cells from endothelial nitric oxide synthase-deficient mice induce vascular dysfunction involving oxidative stress and endothelial arginase I. Redox Biol. 2023;60:102612. doi:10.1016/j.redox.2023.102612
  13. Adefegha SA, Dada FA, Oyeleye SI, Oboh G. Effect of oral berberine administration on the renal profiles of adenosine deaminase, arginase, and nitric oxide in streptozotocin-induced diabetic nephropathy of rats. Comp Clin Path. 2022;31(2):255-263. doi:10.1007/s00580-022-03329-1
  14. Sun Y, Jin D, Zhang Z, et al. Effects of antioxidants on diabetic kidney diseases: mechanistic interpretations and clinical assessment. Chin Med. 2023;18(1):3. doi:10.1186/s13020-022-00700-w
  15. Xu C, Ha X, Yang S, et al. Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms. Front Endocrinol (Lausanne). 2023;14:1232790. doi:10.3389/fendo.2023.1232790
  16. Wang Y, Jin M, Cheng CK, Li Q. Tubular injury in diabetic kidney disease: molecular mechanisms and potential therapeutic perspectives. Front Endocrinol (Lausanne). 2023;14:1238927. doi:10.3389/fendo.2023.1238927
  17. Zhang W, Zheng J, Zhang J, et al. Associations of serum amino acids related to urea cycle with risk of chronic kidney disease in Chinese with type 2 diabetes. Front Endocrinol (Lausanne). 2023;14:1117308. doi:10.3389/fendo.2023.1117308
  18. Li D, Hsu FC, Palmer ND, et al. Multiomics analyses identify AKR1A1 as a biomarker for diabetic kidney disease. Diabetes. 2024;73(7):1188-1195. doi:10.2337/db23-0540
  19. Jin Q, Lau ESH, Luk AO, et al. Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank. Diabetologia. 2024;67(5):837-849. doi:10.1007/s00125-024-06108-5
  20. Dobrijević Z, Stevanović J, Robajac D, et al. Association between nitric oxide synthase (NOS3) gene polymorphisms and diabetic nephropathy: an updated meta-analysis. Mol Cell Endocrinol. 2024;586:112197. doi:10.1016/j.mce.2024.112197
  21. Lopez-Silva C, Surapaneni A, Schmidt IM, et al. Circulating protein and metabolite correlates of histologically confirmed diabetic kidney disease. Kidney Med. 2024;6(12):100920. doi:10.1016/j.xkme.2024.100920
  22. Li X, Zhang X, Wang S, et al. Simultaneous detection of multiple urinary biomarkers in patients with early-stage diabetic kidney disease using Luminex liquid suspension chip technology. Front Endocrinol (Lausanne). 2024;15:1443573. doi:10.3389/fendo.2024.1443573
  23. American Diabetes Association Professional Practice Committee. 11. Chronic kidney disease and risk management: standards of care in diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S219-S230. doi:10.2337/dc24-S011
  24. Luo Y, Zhang W, Qin G. Metabolomics in diabetic nephropathy: unveiling novel biomarkers for diagnosis. Mol Med Rep. 2024;30(3):156. doi:10.3892/mmr.2024.13280
  25. Behnoush AH, Khalaji A, Shokri Varniab Z, et al. Urinary and circulatory netrin-1 as biomarker in diabetes and its related complications: a systematic review and meta-analysis. Endocrine. 2024;84(2):328-344. doi:10.1007/s12020-023-03598-y
  26. Wei L, Gao J, Wang L, Tao Q, Tu C. Multi-omics analysis reveals the potential pathogenesis and therapeutic targets of diabetic kidney disease. Hum Mol Genet. 2024;33(2):122-137. doi:10.1093/hmg/ddad166
  27. Tu QM, Jin HM, Yang XH. Lipid abnormality in diabetic kidney disease and potential treatment advancements. Front Endocrinol (Lausanne). 2025;16:1503711. doi:10.3389/fendo.2025.1503711
  28. Yan X, Zhang X, Li H, et al. Application of proteomics and machine learning methods to study the pathogenesis of diabetic nephropathy and screen urinary biomarkers. J Proteome Res. 2024;23(8):3612-3625. doi:10.1021/acs.jproteome.4c00267
  29. de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association and Kidney Disease: improving global outcomes (KDIGO). Diabetes Care. 2022;45(12):3075-3090. doi:10.2337/dci22-0027