Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2017, vol. 26, nr 8, November, p. 1237–1243

doi: 10.17219/acem/68988

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Influence of glycemic control on some real-time biomarkers of free radical formation in type 2 diabetic patients: An EPR study

Veselina Georgieva Gadjeva1,A,D,F, Petia Goycheva2,A,B,C,D,E, Galina Nikolova3,B,C,D, Antoaneta Zheleva3,D,E

1 Medical Faculty, Trakia University, Stara Zagora, Bulgaria

2 Department of Propedeutics of Internal Diseases, Medical Faculty, Trakia University Hospital, Stara Zagora, Bulgaria

3 Department of Chemistry and Biochemistry, Medical Faculty, Trakia University, Stara Zagora, Bulgaria


Background. The pathology of diabetes is associated with several mechanisms, one of which is oxidative stress (OS). The relationship between OS and diabetic complications has been extensively investigated. OS has been suggested to be involved in the genesis of both macroand microangiopathy. In contrast, the relationship between OS and insulin action is a neglected research area.
Objectives. The aim of this study is to elucidate the effect of glycemic control in type 2 diabetic patients by following the serum levels of some real-time oxidative stress biomarkers.
Material and Methods. The study group consisted of 53 type 2 diabetic patients (31 with poor glycemic control and 22 with good glycemic control) and 24 healthy control subjects. The oxidative stress biomarkers (ROS, Asc• and •NO) were measured by using electron paramagnetic resonance spectroscopy (EPR) methods and compared with clinical parameters.
Results. The statistically significantly higher levels of ROS products and •NO in type 2 diabetic patients in both groups compared to controls mean that the oxidation processes take place at the time the survey is performed. Free radical overproduction persists after the normalization of the glucose levels, and oxidative stress may be involved in the “metabolic memory” effect. This is confirmed by the positive correlation between ROS levels/•NO and average blood glucose levels, triglycerides, and total cholesterol. Furthermore, the low level of the ascorbate radical in both diabetes groups compared to controls confirmed an increase in oxidation processes.
Conclusion. Higher levels of real-time biomarkers show that intensive insulin treatment does not lead to the expected decrease in oxidative processes involving ROS and •NO, probably due to “metabolic memory”.

Key words

diabetes, oxidative stress, free radicals

References (38)

  1. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: How should you do it and what do the results mean? Br J Pharmacol. 2004;142:231–255.
  2. Gadjeva V. Oxidative stress, cancer and chemotherapy. Ac Publ Tr Univer St. Zagora. 2007.
  3. Shin CS, Moon BS, Park KS, et al. Serum 8-hydroxy-guanine levels are increased in diabetic patients. Diabetes. 2001;24:733–737.
  4. Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S. Reduced β-cell mass and expression of oxidative stress related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia. 2002;45:85–96.
  5. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 5th ed. New York, NY: Oxford University Press; 2015.
  6. Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015;5:194–222.
  7. Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: Implications for vascular and other complications. IJMS. 2013;14:21525–21550.
  8. Gruden G, Barutta F, Kunos G, Pacher P. Role of the endocannabinoid system in diabetes and diabetic complications. Br J Pharmacol. 2016;173(7):1116–1127.
  9. Ido Y. Diabetic complications within the context of ageing: NADH/ NAD+ redox, insulin C‐peptide, SIRT1‐LKB1‐AMPK positive feedback and FOXO3. J Diabetes Investig. 2016;7(4):448–458.
  10. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circulation research. 2010,107:1058–1070.
  11. Zheleva A. Electron paramagnetic resonance-oxidative status and antioxidant activity. Ac Publ Tr Univer St. Zagora. 2012:44–55.
  12. Bailey DM. Ascorbate, blood-brain barrier function and acute mountain sickness: A radical hypothesis. Wilderness & environmental medicine. 2004;15:231–233.
  13. Shi H, Sui Y, Wang X, Luo Yi, Ji L. Hydroxyl radical production and oxidative damage induced by cadmium and naphthalene in liver of Carassius auratus. Comp Biochem Physiol Part C Toxicol Pharmcol. 2005;140:115–121.
  14. Yoshioka T, Iwamoto N, Ito K. An application of electron paramagnetic resonance to evaluate nitric oxide and its quenchers. J Am Soc Nephrol. 1996;7:961–965.
  15. Yokoyama K, Hashiba K, Wakabayashi H, et al. Inhibition of LPS-stimulated NO production in mouse macrophage-like cells by Tropolones.Anticancer Research. 2004;24:3917–3922.
  16. Robertson RP, Harmon J, Tran PO, Poitout V. β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004;53:119–124.
  17. Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 2005;54:1615–1625.
  18. Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Physical Therapy. 2008;88:1322–1335.
  19. Ceriello A. The hyperglycemia-induced metabolic memory: The new challenge for the prevention of CVD in diabetes. Revista Española de Cardiología. 2008;8(Suppl C):11–17.
  20. Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 2005;54(6):1615–1625.
  21. Piwowar A, Knapik-Kordecka M, Warwas M. AOPP and its relations with selected markers of oxidative/antioxidative system in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2007,77(2):188–192.
  22. Mason RP, Hanna PM, Burkitt MJ, Kadiiska MB. Detection of oxygen-derived radicals in biological systems using electron spin resonance. Environ Health Perspect. 1994;102:33.
  23. Luo Y, Roth GS. The roles of dopamine oxidative stress and dopamine receptor signaling in aging and age-related neurodegeneration. ARS. 2000;2:449–460.
  24. Aschner PJ, Ruiz AJ. Metabolic memory for vascular disease in diabetes. Diabetes Technol Ther. 2012;14(Suppl 1):68–74.
  25. Takeshita K, Fujii K, Anzai K, Ozawa T. In vivo monitoring of hydroxyl radical generation caused by X-ray irradiation of rats using the spin trapping/EPR technique. Free Rad Biol Med. 2004;36:1134–1143.
  26. Armstrong D. Oxidative Stress Biomarkers and Antioxidant Protocols. Totowa, NJ: Humana Press; 2002:186.
  27. Buettner GR, Jurkiewicz BA. Ascorbate free radical as a marker of oxidative stress: An EPR study. Free Rad Biol and Med. 1993;14:49–55.
  28. Nakagawa K, Kanno H, Miura Y. Detection and analyses of ascorbyl radical in cerebrospinal fluid and serum of acute lymphoblastic leukemia. Anal Biochem. 1997;254:31–35.
  29. Chen Q, Espey MG, Sun AY, et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA. 2007;104:8749–8754.
  30. Buettner GR. Workshop: Rigorous Detection and Identification of Free Radicals in Biology and Medicine. SFRBM 2015, November.
  31. Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress: A concise review. Saudi Pharm J. 2016;24(5):547–553.
  32. Vinish M, Anand A, Prabhakar S. Altered oxidative stress levels in Indian Parkinson’s disease patients with PARK2 mutations. Acta Biochim Pol. 2011;58:165–169.
  33. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107:1058–1070.
  34. Chang Yi-Ch, Chuang Lee-M. The role of oxidative stress in the pathogenesis of type 2 diabetes: From molecular mechanism to clinical implication. Am J Transl Res. 2010;2:316–331.
  35. Henry Y, Guissani A. Contribution of spin-trapping EPR techniques for the measurement of NO production in biological systems. Analusis. 2000;28:445–454.
  36. Gradinaru D, Borsa C, Ionescu C, Margina D. Advanced oxidative and glycoxidative protein damage markers in the elderly with type 2 diabetes. Journal of Proteomics. 2013;92:313–322.
  37. Gradinaru D, Borsa C, Ionescu C, Prada GI. Oxidized LDL and NO synthesis – biomarkers of endothelial dysfunction and ageing. Mech Ageing Dev. 2015;151:101–113.
  38. Monnier L, Colette C, Michel F, Cristol JP, Owens DR. Insulin therapy has a complex relationship with measure of oxidative stress in type 2 diabetes: A case for further study. Diab Metab Res Rev. 2011;27:348–353.