Journals / Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi / 2026 / Cilt: 57 Sayı: 1

ASSOCIATION OF SERUM HEME OXYGENASE-1 (HO-1) ENZYME WITH GLYCEMIC CONTROL IN DIABETIC WOMEN

DİYABETİK KADINLARDA SERUM HEM OKSİJENAZ-1 (HO-1) ENZİMİNİN GLİSEMİK KONTROL İLE İLİŞKİSİ

Osman Sağlam(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, KAYSERİ ŞEHİR SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ)0000-0003-0779-992X
Neşe Ersöz Gülçelik(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, GÜLHANE TIP FAKÜLTESİ, GÜLHANE TIP PR. (ANKARA))0000-0001-8212-5752
Tülay Omma(Ankara Eğitim ve Araştırma Hastanesi)0000-0002-2557-9499
Gül Gürsoy(Ankara Eğitim ve Araştırma Hastanesi)0000-0003-2647-694X
Pages
20–24
Publication Date
2024-04-30
🏛️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)

This suggests that the relationship between serum ferritin and glycemic parameters may not be directly associated with the breakdown of heme molecules by heme oxygenase-1.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Aim: The rapidly increasing prevalence of diabetes has made it a significant global health issue.
📊
Key Findings & Data:The heme molecule broken down by heme oxygenase-1 produces CO, bilirubin, and Fe/ferritin.
💡
Conclusion & Impact:This suggests that the relationship between serum ferritin and glycemic parameters may not be directly associated with the breakdown of heme molecules by heme oxygenase-1.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:hem oksijenaz-1 · diabetes mellitus · ferritin

Abstract

Aim: The rapidly increasing prevalence of diabetes has made it a significant global health issue. While there are existing treatment options, there is a need for innovative approaches to treatment. The heme molecule broken down by heme oxygenase-1 produces CO, bilirubin, and Fe/ferritin. Animal experiments have shown that products resulting from heme oxygenase-1 induction attenuate inflammation, oxidative stress and apoptosis and reduce hyperglycemia. We aimed to investigate whether serum heme oxygenase-1 has an effect on glycemic status in women with diabetes. Material and methods: Sixty-three female patients (31 diabetic and 32 control) who applied to the outpatient clinic were included in the study. The study excluded patients with acute and chronic renal failure, patients with acute or chronic liver disease, patients with acute infection, patients with a body mass index (BMI) of ≤18 kg/m2 or ≥35 kg/m2, and patients younger than 18 years and older than 65 years. Results: Serum ferritin was significantly higher in the patient group compared to the control group (p = 0.028). Serum total bilirubin and serum heme oxygenase-1 were similar in the two groups (p = 0.260, p = 0.426, respectively). Conclusion: In our study, serum ferritin were significantly higher in the diabetes group than controls, supporting a possible role for ferritin in diabetes pathogenesis. Nevertheless, no considerable differences were observed in serum total bilirubin and serum heme oxygenase-1 between the groups. This suggests that the relationship between serum ferritin and glycemic parameters may not be directly associated with the breakdown of heme molecules by heme oxygenase-1.

Özet

Amaç: Diyabetin hızla artan prevalansı, onu önemli bir küresel sağlık sorunu haline getirmiştir. Mevcut tedavi seçenekleri olsa da, tedavide yenilikçi yaklaşımlara ihtiyaç vardır. Hem molekülünün hem oksijenaz-1 ile parçalanması sonucu CO, bilirubin ve Fe/Ferritin ortaya çıkar. Yapılan hayvan deneyleri, hem oksijenaz-1 indüksiyonu sonucu ortaya çıkan ürünlerin inflamasyon, oksidatif stres ve apoptozu hafiflettiği ve hiperglisemiyi azalttığı gösterilmiştir. Bizde, diyabetli kadınlarda glisemik durum üzerine serum hem oksijenaz-1'in etkisinin olup olmadığını incelemeyi amaçladık. Gereç ve yöntem: Polikliniğe başvuran 63 kadın hasta (31'i diyabetik, 32'si kontrol) çalışmaya dahil edilmiştir. Çalışmaya akut ve kronik böbrek yetmezliği olan hastalar, akut veya kronik karaciğer hastalığı olan hastalar, akut enfeksiyonu olan hastalar, vücut kitle indeksi (VKİ) ≤18 kg/m2 veya ≥35 kg/m2 olan hastalar ve 18 yaşından küçük ve 65 yaşından büyük hastalar dahil edilmemiştir. Bulgular: Serum ferritin hasta grubunda kontrol grubuna kıyasla anlamlı olarak daha yüksekti (p = 0.028). Serum total bilirubin ve serum hem oksijenaz-1 iki grupta benzerdi (sırasıyla p = 0.260, p = 0.426). Sonuç: Çalışmamızda diyabet grubundaki serum ferritin düzeyinin kontrol grubuna göre anlamlı ölçüde daha yüksek olması ferritinin diyabet patogenezindeki olası rolünü desteklemektedir. Bununla birlikte, serum total bilirubin düzeyleri ve serum hem oksijenaz-1 düzeylerinde gruplar arasında önemli bir fark gözlenmemiştir. Bu durum, serum ferritin ile glisemik parametreler arasındaki ilişkinin doğrudan hem moleküllerinin hem oksijenaz-1 tarafından parçalanması ile ilişkili olmayabileceğini düşündürmektedir.

🔖

Cite This Article

Sağlam, O., Gülçelik, N. E., Omma, T., Karaca, A., Aral, Y., Gürsoy, G. (2024). ASSOCIATION OF SERUM HEME OXYGENASE-1 (HO-1) ENZYME WITH GLYCEMIC CONTROL IN DIABETIC WOMEN. Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi, Cilt: 57 Sayı: 1, 20–24. https://doi.org/10.20492/aeahtd.1377001

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (41)

  1. Bonnefont-Rousselot D, Beaudeux JL, Thérond P, Peynet J, Legrand A, Delattre J. Diabetes mellitus, oxidative stress and advanced glycation endproducts. Ann Pharm Fr. 2004;62(3):147-157.
  2. Darenskaya MA, Kolesnikova LI, Kolesnikov SI. Oxidative Stress: Pathogenetic Role in Diabetes Mellitus and Its Complications and Therapeutic Approaches to Correction. Bull Exp Biol Med. 2021;171(2):179-189. https://doi:10.1007/s10517-021-05191-7
  3. Tiwari S, Ndisang J. The Heme Oxygenase System and Type-1 Diabetes. Curr Pharm Des. 2014;20(9):1328-1337. https://do i:10.2174/13816128113199990552
  4. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. https://doi:10.1016/j.diabres.2019.107843
  5. Shah N, Abdalla MA, Deshmukh H, Sathyapalan T. Therapeutics for type-2 diabetes mellitus: a glance at the recent inclusions and novel agents under development for use in clinical practice. Ther Adv Endocrinol Metab. 2021;12:20420188211042145. https:// doi:10.1177/20420188211042145
  6. Yoshida T, Kikuchi G. Reaction of the microsomal heme oxygenase with cobaltic protoporphyrin IX, an extremely poor substrate. Journal of Biological Chemistry. 1978;253(23):8479-8482. https:// doi:10.1016/s0021-9258(17)34316-8
  7. Campbell NK, Fitzgerald HK, Dunne A. Regulation of inflammation by the antioxidant haem oxygenase 1. Nat Rev Immunol. 2021;21(7):411-425. https://doi:10.1038/s41577-020-00491-x
  8. Chen QY, Wang GG, Li W, Jiang YX, Lu XH, Zhou PP. Heme oxygenase-1 promotes delayed wound healing in diabetic rats. J Diabetes Res. 2016;2016:9726503. https:// doi:10.1155/2016/9726503
  9. Abraham NG, Drummond GS, Lutton JD, Kappas A. The biological significance and physiological role of heme oxygenase. Cellular Physiology and Biochemistry. 1996;6(3):129-168. https:// doi:10.1159/000154819
  10. Kikuchi G, Yoshida T, Noguchi M. Heme oxygenase and heme degradation. Biochem Biophys Res Commun. 2005;338(1):558-567. https://doi:10.1016/j.bbrc.2005.08.020
  11. Milani M, Pesce A, Nardini M, et al. Structural bases for heme binding and diatomic ligand recognition in truncated hemoglobins. J Inorg Biochem. 2005;99(1):97-109. https://doi:10.1016/j. jinorgbio.2004.10.035
  12. Vile GF, Basu-Modak S, Waltner C, Tyrrell RM. Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts. Proc Natl Acad Sci U S A. 1994;91(7):2607- 2610. https://doi:10.1073/pnas.91.7.2607
  13. Nocentini A, Bonardi A, Pratesi S, Gratteri P, Dani C, Supuran CT. Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin. J Enzyme Inhib Med Chem. 2022;37(1):487-501. https://doi:10.108 0/14756366.2021.2020773
  14. Mishra M, Ndisang J. A Critical and Comprehensive Insight on Heme Oxygenase and Related Products Including Carbon Monoxide, Bilirubin, Biliverdin and Ferritin in Type-1 and Type-2 Diabetes. Curr Pharm Des. 2014;20(9):1370-1391. https://doi:10.217 4/13816128113199990559
  15. Andrews M, Leiva E, Arredondo-Olguín M. Short repeats in the heme oxygenase 1 gene promoter is associated with increased levels of inflammation, ferritin and higher risk of type-2 diabetes mellitus. Journal of Trace Elements in Medicine and Biology. 2016;37:25-30. https://doi:10.1016/j.jtemb.2016.06.001
  16. Bao W, Song F, Li X, et al. Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes mellitus: A HuGE review and meta-analysis. Am J Epidemiol. 2010;172(6):631-636. https://doi:10.1093/aje/kwq162
  17. Chen YH, Chau LY, Chen JW, Lin SJ. Serum bilirubin and ferritin levels link heme oxygenase-1 gene promoter polymorphism and susceptibility to coronary artery disease in diabetic patients. Diabetes Care. 2008;31(8):1615-1620. https://doi:10.2337/dc07- 2126
  18. Lee EY, Lee YH, Kim SH, et al. Association between heme oxygenase-1 promoter polymorphisms and the development of albuminuria in type 2 diabetes: A case-control study. Medicine (United States). 2015;94(43):e1825. https://doi:10.1097/ MD.0000000000001825
  19. Wu R, Zhu Z, Zhou D. VEGF, apelin and HO-1 in diabetic patients with retinopathy: A correlation analysis. BMC Ophthalmol. 2020;20(1):1-6. https://doi:10.1186/s12886-020-01593-9
  20. Hong J, Kim YH. Fatty Liver/Adipose Tissue Dual-Targeting Nanoparticles with Heme Oxygenase-1 Inducer for Amelioration of Obesity, Obesity-Induced Type 2 Diabetes, and Steatohepatitis. Advanced Science. 2022;9(33):2203286. https:// doi:10.1002/advs.202203286
  21. Fan J, Xu G, Jiang T, Qin Y. Pharmacologic induction of heme oxygenase-1 plays a protective role in diabetic retinopathy in rats. Invest Ophthalmol Vis Sci. 2012;53(10):6541-6556. https:// doi:10.1167/iovs.11-9241
  22. Negi G, Nakkina V, Kamble P, Sharma SS. Heme oxygenase- 1, a novel target for the treatment of diabetic complications: Focus on diabetic peripheral neuropathy. Pharmacol Res. 2015;102:158-167. https://doi:10.1016/j.phrs.2015.09.014
  23. Li M, Kim DH, Tsenovoy PL, et al. Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance. Diabetes. 2008;57(6):1526-1535. https://doi:10.2337/db07-1764
  24. Castilho ÁF, Aveleira CA, Leal EC, et al. Heme oxygenase- 1 protects retinal endothelial cells against high glucose- and oxidative/nitrosative stress-induced toxicity. PLoS One. 2012;7(8):e42428. https://doi:10.1371/journal.pone.0042428
  25. Thorand B, Löwel H, Schneider A, et al. C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: Results from the MONICA Augsburg Cohort Study, 1984- 1998. Arch Intern Med. 2003;163(1):93-99. https://doi:10.1001/ archinte.163.1.93
  26. Soinio M, Marniemi J, Laakso M, Lehto S, R̈onnemaa T. High-sensitivity C-reactive protein and coronary heart disease mortality in patients with type 2 diabetes: A 7-year follow-up study. Diabetes Care. 2006;29(2):329-333. https://doi:10.2337/ diacare.29.02.06.dc05-1700
  27. Liu Q, Jiang CY, Chen BX, Zhao W, Meng D. The association between high-sensitivity C-reactive protein concentration and diabetic nephropathy: A meta-analysis. Eur Rev Med Pharmacol Sci. 2015;19(23):4558-4568.
  28. Hayashino Y, Mashitani T, Tsujii S, Ishii H. Serum high- sensitivity C-reactive protein levels are associated with high risk of development, not progression, of diabetic nephropathy among Japanese type 2 diabetic patients: A prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT7]). Diabetes Care. 2014;37(11):2947-2952. https://doi:10.2337/dc14- 1357
  29. Ma H, Lin H, Hu Y, et al. Serum ferritin levels are associated with insulin resistance in Chinese men and post-menopausal women: The Shanghai Changfeng study. British Journal of Nutrition. 2018;120(8):863-871. https://doi:10.1017/S0007114518002167
  30. Chen L, Li Y, Zhang F, Zhang S, Zhou X, Ji L. Association of serum ferritin levels with metabolic syndrome and insulin resistance in a Chinese population. J Diabetes Complications. 2017;31(2):364-368. https://doi:10.1016/j.jdiacomp.2016.06.018
  31. Forouhi NG, Harding AH, Allison M, et al. Elevated serum ferritin levels predict new-onset type 2 diabetes: Results from the EPIC-Norfolk prospective study. Diabetologia. 2007;50(5):949- 956. https://doi:10.1007/s00125-007-0604-5
  32. Arredondo M, Fuentes M, Jorquera D, et al. Cross-talk between body iron stores and diabetes: Iron stores are associated with activity and microsatellite polymorphism of the heme oxygenase and type 2 diabetes. Biol Trace Elem Res. 2011;143(2):625- 636. https://doi:10.1007/s12011-010-8895-7
  33. Wei Y, Liu C, Lai F, et al. Associations between serum total bilirubin, obesity and type 2 diabetes. Diabetol Metab Syndr. 2021;13(1):1-7. https://doi:10.1186/s13098-021-00762-0
  34. Oda E. Cross-Sectional and Longitudinal Associations between Serum Bilirubin and Prediabetes in a Health Screening Population. Can J Diabetes. 2016;40(3):270-275. https://doi: 10.1016/j.jcjd.2016.01.001
  35. Wang J, Li Y, Han X, et al. Serum bilirubin levels and risk of type 2 diabetes: Results from two independent cohorts in middle-aged and elderly Chinese. Sci Rep. 2017;7:41338. https:// doi:10.1038/srep41338
  36. Choi SW, Lee YH, Kweon SS, et al. Association between total bilirubin and hemoglobin A1c in Korean type 2 diabetic 24 patients. J Korean Med Sci. 2012;27(10):1196. https://doi:10.3346/ jkms.2012.27.10.1196
  37. Kawamoto R, Ninomiya D, Senzaki K, Kumagi T. Mildly elevated serum total bilirubin is negatively associated with hemoglobin A1c independently of confounding factors among community-dwelling middle-aged and elderly persons. J Circ Biomark. 2017;6:1849454417726609. https:// doi:10.1177/1849454417726609
  38. Huang SS, Chan WL, Leu HB, Huang PH, Lin SJ, Chen JW. Serum bilirubin levels predict future development of metabolic syndrome in healthy middle-aged nonsmoking men. American Journal of Medicine. 2015;128(10):1138-e35. https://doi:10.1016/j.amjmed. 2015.04.019
  39. Jo J, Yun JE, Lee H, Kimm H, Jee SH. Total, direct, and indirect serum bilirubin concentrations and metabolic syndrome among the Korean population. Endocrine. 2011;39(2):182-189. https:// doi:10.1007/s12020-010-9417-2
  40. Oda E, Aizawa Y. Total bilirubin is inversely associated with metabolic syndrome but not a risk factor for metabolic syndrome in Japanese men and women. Acta Diabetol. 2013;50(3):417-422. https:// doi:10.1007/s00592-012-0447-5
  41. Wu Y, Li M, Xu M, et al. Low serum total bilirubin concentrations are associated with increased prevalence of metabolic syndrome in Chinese. J Diabetes. 2011;3(3):217-224. https://doi:10.1111/ j.1753-0407.2011.00138.x