Araştırma Makalesi
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Dynamic Thiol/Disulfide Homeostasis as a Complementary Oxidative Stress Marker Across Albuminuria Stages in Type 2 Diabetes Mellitus

Yıl 2026, Cilt: 33 Sayı: 1, 71 - 77, 21.03.2026
https://doi.org/10.17343/sdutfd.1767002
https://izlik.org/JA26SP76ZF

Öz

Objective
Diabetic nephropathy (DN) remains one of the most
serious complications of type 2 diabetes mellitus
(T2DM). Traditionally, disease progression has
been evaluated through albuminuria, yet increasing
evidence highlights the role of oxidative stress and
redox imbalance in DN pathogenesis. The present
study was designed to evaluate dynamic thiol/disulfide
homeostasis across albuminuria stages and to explore
its potential role as a complementary systemic oxidative
stress marker alongside albuminuria in T2DM.

Material and Method
A total of 122 individuals were included and categorized
into four study groups: 30 healthy participants (Group
1), 31 normoalbuminuric diabetic patients (Group 2),
31 patients with microalbuminuria (Group 3), and 30
patients with macroalbuminuria (Group 4). Plasma
thiol/disulfide parameters were measured using the
automated method developed by Erel and Neselioglu,
while urinary albumin concentrations were determined
by immunoturbidimetric assay.

Results
Progressive decreases in both native and total thiol
levels were observed with advancing severity of
albuminuria (p<0.001). Disulfide concentrations
showed a downward trend in macroalbuminuric
patients (p=0.019), although disulfide-related ratios
remained largely unchanged across the groups.
Correlation analyses identified significant negative
associations between thiol concentrations and
diabetes duration, HbA1c, as well as CRP levels
(p<0.001).

Conclusion
Dynamic thiol/disulfide balance reflects systemic
oxidative stress but cannot fully substitute for
albuminuria as a marker of DN. Instead, it appears
to provide complementary insight into oxidative
mechanisms associated with DN severity in T2DM
patients.

Etik Beyan

This study was approved by the Suleyman Demirel University Clinical Research Ethics Committee (Date: 15.04.2020, No: 72867572.050.01.04). The study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent to participate and publish was obtained from all individual participants or legal guardians included in the study.

Destekleyen Kurum

This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.

Kaynakça

  • 1. Zhazykbayeva S, Pabel S, Mügge A, et al. The molecular mechanisms associated with the physiological responses to inflammation and oxidative stress in cardiovascular diseases. Biophysical Reviews 2020;12(4):947-68.
  • 2. Tan BL, Norhaizan ME, Liew WPP. Nutrients and oxidative stress: friend or foe? Oxidative medicine and cellular longevity 2018;2018(1):9719584.
  • 3. Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World Journal of Diabetes 2015;6(3):456.
  • 4. Sharifi-Rad M, Anil Kumar NV, Zucca P, et al. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Frontiers In Physiology 2020;11:552535.
  • 5. Fass D, Thorpe C. Chemistry and enzymology of disulfide cross-linking in proteins. Chemical Reviews 2018;118(3):1169-98.
  • 6. Di Meo S, Reed TT, Venditti P, et al. Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Medicine and Cellular Longevity 2016;2016(1):1245049.
  • 7. Young I, Woodside J. Antioxidants in health and disease. Journal Of Clinical Pathology 2001;54(3):176-86.
  • 8. Şener MU, Sönmez Ö, Keyf İA, et al. Evaluation of thiol/disulfide homeostasis in lung cancer. Turkish Thoracic Journal 2020;21(4):255.
  • 9. Rodrigues SD, Batista GB, Ingberman M, et al. Plasma cysteine/ cystine reduction potential correlates with plasma creatinine levels in chronic kidney disease. Blood Purification 2013;34(3-4):231-7.
  • 10. Go Y-M, Jones DP. Cysteine/cystine redox signaling in cardiovascular disease. Free Radical Biology and Medicine 2011;50(4):495-509.
  • 11. Dogru A, Balkarli A, Cetin GY, et al. Thiol/disulfide homeostasis in patients with ankylosing spondylitis. Bosnian Journal of Basic Medical Sciences 2016;16(3):187.
  • 12. Ates I, Kaplan M, Yuksel M, et al. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine 2016;51(1):47-51.
  • 13. Sonmez MG, Kozanhan B, Deniz ÇD, et al. Dynamic thiol/disulfide homeostasis as a novel indicator of oxidative stress in patients with urolithiasis. Investigative and Clinical Urology 2019;60(4):258-66.
  • 14. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clinical Biochemistry 2014;47(18):326- 32.
  • 15. Eijkelkamp WB, Zhang Z, Brenner BM, et al. Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies. Journal of Hypertension 2007;25(4):871-6.
  • 16. Lee ET, Howard BV, Wang W, et al. Prediction of coronary heart disease in a population with high prevalence of diabetes and albuminuria: the Strong Heart Study. Circulation 2006;113(25):2897-905.
  • 17. Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules 2010;15(12):8890-903.
  • 18. Yazıcı AE, Paşaoğlu H, Yücel D, et al. Tip II Diabetes Mellituslu Hastalarda Plazma Total Tiyol ve Eritrosit Redükte Glutatyon Düzeyleri. Turkiye Klinikleri Journal of Medical Sciences 2002;22(5):487-92.
  • 19. Karacan G, Ercan N, Bostanci I, et al. A novel oxidative stress marker of atopic dermatitis in infants: Thiol–disulfide balance. Archives Of Dermatological Research 2020;312(10):697-703.
  • 20. Rana R, Kamath SU, Shastri BA, et al. Evaluation of thiol/disulfide homeostasis and ischemia-modified albumin in metabolic syndrome patients. Advances In Redox Research 2025;14:100116.
  • 21. Ertop ZŞT, Aslan N, Neşelioğlu S, et al. Thiol/Disulfide Homeostasis: A New Oxidative Marker in Heart Failure Patients with Preserved Ejection Fraction. Anatolian Journal of Cardiology 2024;28(8):406.
  • 22. Awanti SM, Baruah PS, Prakash M. Serum and urine protein thiols in type 2 diabetes mellitus patients. Indian journal of physiology and pharmacology 2009;53(2):185-8.
  • 23. Prakash M, Shetty J, Rao L, et al. Serum paraoxonase activity and protein thiols in chronic renal failure patients. Indian Journal of Nephrology 2008;18(1):13-6.
  • 24. Singh DK, Winocour P, Summerhayes B, et al. Prevalence and progression of peripheral vascular calcification in type 2 diabetes subjects with preserved kidney function. Diabetes Research and Clinical Practice 2012;97(1):158-65.
  • 25. Ates I, Kaplan M, Inan B, et al. How does thiol/disulfide homeostasis change in prediabetic patients? Diabetes research and clinical practice 2015;110(2):166-71.

Dynamic Thiol/Disulfide Homeostasis as a Complementary Oxidative Stress Marker Across Albuminuria Stages in Type 2 Diabetes Mellitus

Yıl 2026, Cilt: 33 Sayı: 1, 71 - 77, 21.03.2026
https://doi.org/10.17343/sdutfd.1767002
https://izlik.org/JA26SP76ZF

Öz

Objective
Diabetic nephropathy (DN) remains one of the most
serious complications of type 2 diabetes mellitus
(T2DM). Traditionally, disease progression has
been evaluated through albuminuria, yet increasing
evidence highlights the role of oxidative stress and
redox imbalance in DN pathogenesis. The present
study was designed to evaluate dynamic thiol/disulfide
homeostasis across albuminuria stages and to explore
its potential role as a complementary systemic oxidative
stress marker alongside albuminuria in T2DM.

Material and Method
A total of 122 individuals were included and categorized
into four study groups: 30 healthy participants (Group
1), 31 normoalbuminuric diabetic patients (Group 2),
31 patients with microalbuminuria (Group 3), and 30
patients with macroalbuminuria (Group 4). Plasma
thiol/disulfide parameters were measured using the
automated method developed by Erel and Neselioglu,
while urinary albumin concentrations were determined
by immunoturbidimetric assay.

Results
Progressive decreases in both native and total thiol
levels were observed with advancing severity of
albuminuria (p<0.001). Disulfide concentrations
showed a downward trend in macroalbuminuric
patients (p=0.019), although disulfide-related ratios
remained largely unchanged across the groups.
Correlation analyses identified significant negative
associations between thiol concentrations and
diabetes duration, HbA1c, as well as CRP levels
(p<0.001).

Conclusion
Dynamic thiol/disulfide balance reflects systemic
oxidative stress but cannot fully substitute for
albuminuria as a marker of DN. Instead, it appears
to provide complementary insight into oxidative
mechanisms associated with DN severity in T2DM
patients.

Etik Beyan

This study was approved by the Suleyman Demirel University Clinical Research Ethics Committee (Date: 15.04.2020, No: 72867572.050.01.04). The study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent to participate and publish was obtained from all individual participants or legal guardians included in the study.

Destekleyen Kurum

This research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors.

Kaynakça

  • 1. Zhazykbayeva S, Pabel S, Mügge A, et al. The molecular mechanisms associated with the physiological responses to inflammation and oxidative stress in cardiovascular diseases. Biophysical Reviews 2020;12(4):947-68.
  • 2. Tan BL, Norhaizan ME, Liew WPP. Nutrients and oxidative stress: friend or foe? Oxidative medicine and cellular longevity 2018;2018(1):9719584.
  • 3. Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World Journal of Diabetes 2015;6(3):456.
  • 4. Sharifi-Rad M, Anil Kumar NV, Zucca P, et al. Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Frontiers In Physiology 2020;11:552535.
  • 5. Fass D, Thorpe C. Chemistry and enzymology of disulfide cross-linking in proteins. Chemical Reviews 2018;118(3):1169-98.
  • 6. Di Meo S, Reed TT, Venditti P, et al. Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Medicine and Cellular Longevity 2016;2016(1):1245049.
  • 7. Young I, Woodside J. Antioxidants in health and disease. Journal Of Clinical Pathology 2001;54(3):176-86.
  • 8. Şener MU, Sönmez Ö, Keyf İA, et al. Evaluation of thiol/disulfide homeostasis in lung cancer. Turkish Thoracic Journal 2020;21(4):255.
  • 9. Rodrigues SD, Batista GB, Ingberman M, et al. Plasma cysteine/ cystine reduction potential correlates with plasma creatinine levels in chronic kidney disease. Blood Purification 2013;34(3-4):231-7.
  • 10. Go Y-M, Jones DP. Cysteine/cystine redox signaling in cardiovascular disease. Free Radical Biology and Medicine 2011;50(4):495-509.
  • 11. Dogru A, Balkarli A, Cetin GY, et al. Thiol/disulfide homeostasis in patients with ankylosing spondylitis. Bosnian Journal of Basic Medical Sciences 2016;16(3):187.
  • 12. Ates I, Kaplan M, Yuksel M, et al. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine 2016;51(1):47-51.
  • 13. Sonmez MG, Kozanhan B, Deniz ÇD, et al. Dynamic thiol/disulfide homeostasis as a novel indicator of oxidative stress in patients with urolithiasis. Investigative and Clinical Urology 2019;60(4):258-66.
  • 14. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clinical Biochemistry 2014;47(18):326- 32.
  • 15. Eijkelkamp WB, Zhang Z, Brenner BM, et al. Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies. Journal of Hypertension 2007;25(4):871-6.
  • 16. Lee ET, Howard BV, Wang W, et al. Prediction of coronary heart disease in a population with high prevalence of diabetes and albuminuria: the Strong Heart Study. Circulation 2006;113(25):2897-905.
  • 17. Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules 2010;15(12):8890-903.
  • 18. Yazıcı AE, Paşaoğlu H, Yücel D, et al. Tip II Diabetes Mellituslu Hastalarda Plazma Total Tiyol ve Eritrosit Redükte Glutatyon Düzeyleri. Turkiye Klinikleri Journal of Medical Sciences 2002;22(5):487-92.
  • 19. Karacan G, Ercan N, Bostanci I, et al. A novel oxidative stress marker of atopic dermatitis in infants: Thiol–disulfide balance. Archives Of Dermatological Research 2020;312(10):697-703.
  • 20. Rana R, Kamath SU, Shastri BA, et al. Evaluation of thiol/disulfide homeostasis and ischemia-modified albumin in metabolic syndrome patients. Advances In Redox Research 2025;14:100116.
  • 21. Ertop ZŞT, Aslan N, Neşelioğlu S, et al. Thiol/Disulfide Homeostasis: A New Oxidative Marker in Heart Failure Patients with Preserved Ejection Fraction. Anatolian Journal of Cardiology 2024;28(8):406.
  • 22. Awanti SM, Baruah PS, Prakash M. Serum and urine protein thiols in type 2 diabetes mellitus patients. Indian journal of physiology and pharmacology 2009;53(2):185-8.
  • 23. Prakash M, Shetty J, Rao L, et al. Serum paraoxonase activity and protein thiols in chronic renal failure patients. Indian Journal of Nephrology 2008;18(1):13-6.
  • 24. Singh DK, Winocour P, Summerhayes B, et al. Prevalence and progression of peripheral vascular calcification in type 2 diabetes subjects with preserved kidney function. Diabetes Research and Clinical Practice 2012;97(1):158-65.
  • 25. Ates I, Kaplan M, Inan B, et al. How does thiol/disulfide homeostasis change in prediabetic patients? Diabetes research and clinical practice 2015;110(2):166-71.
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Nefroloji
Bölüm Araştırma Makalesi
Yazarlar

Atila Altuntaş 0000-0001-9196-3133

Bünyamin Aydın 0000-0003-2059-1074

Sıddıka Ersoy 0000-0001-8094-8042

Özcan Erel 0000-0002-2996-3236

Hasret Demirel 0000-0002-5548-3797

Şeniz Tutum 0009-0000-5989-7340

Gönderilme Tarihi 16 Ağustos 2025
Kabul Tarihi 13 Şubat 2026
Yayımlanma Tarihi 21 Mart 2026
DOI https://doi.org/10.17343/sdutfd.1767002
IZ https://izlik.org/JA26SP76ZF
Yayımlandığı Sayı Yıl 2026 Cilt: 33 Sayı: 1

Kaynak Göster

Vancouver 1.Atila Altuntaş, Bünyamin Aydın, Sıddıka Ersoy, Özcan Erel, Hasret Demirel, Şeniz Tutum. Dynamic Thiol/Disulfide Homeostasis as a Complementary Oxidative Stress Marker Across Albuminuria Stages in Type 2 Diabetes Mellitus. SDÜ Tıp Fak Derg. 01 Mart 2026;33(1):71-7. doi:10.17343/sdutfd.1767002

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