Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis

Open access

Abstract

Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls.

Materials and methods. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here.

Results. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA).

Conclusions. Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

1. STROM JL, EGEDE LE. The impact of social support on outcomes in adult patients with type 2 diabetes: a systematic review. Curr Diab Rep. 2012 Dec; 12(6):769-81.

2. ZIMMET P, ALBERTI KG, SHAW J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414:782-787.

3. HOSSAIN P, KAWAR B, ELNAHAS M. Obesity and diabetes in the developing world - A growing challenge. N Engl J Med. 2007; 3 56:213-215.

4. ANGULO P. Nonalcoholic fatty liver disease. N Engl J Med. 2002; 346:1221-1231.

5. YKI-JARVINEN H. Non-alcoholic fatty liver as a cause and cosequence of the metabolic syndrome. Lancet Diabetes Endocrinol. 2014; 2:901-910.

6. DAOUSSI C, CASSON IF, GILL GV, MACFARLANE IA, WIELDING JPH, PINKNEI JH. Prevalence of obesity in type 2 diabetes in secondary care: Association with cardiovascular risk factors. Postgrad Med J. 2006; 82:280-284.

7. STIUSO P, SCOGNAMIGLIO I, MUROLO M, FERRANTI P, DE SIMONE C, RIZZO MR, TUCCILLO C, CARAGLIA M, LOGUERCIO C, FEDERICO A. Serum oxidative stress markers and lipidomic profile to detect NASH patients responsive to an antioxidant treatment: a pilot study. Oxid Med Cell Longev. 2014; 2014:169216, 8 pages (1-8).

8. RUST C, GORES GJ. Apoptosis and liver disease. Am J Med. 2000; 108:567-574.

9. HALLIWELL B. Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans. Free Radic Res. 1996; 25:57-74.

10. ALBERTI KG, ECKEL RH, GRUNDY SM, ZIMMET PZ, CLEEMAN JI, DONATO KA, FRUCHART JC, JAMES WP, LORIA CM, SMITH SC JR; INTERNATIONAL DIABETES FEDERATION TASK FORCE ON EPIDEMIOLOGY AND PREVENTION; NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; AMERICAN HEART ASSOCIATION; WORLD HEART FEDERATION; INTERNATIONAL ATHEROSCLEROSIS SOCIETY; INTERNATIONAL ASSOCIATION FOR THE STUDY OF OBESITY. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation task force on epidemiology and prevention. Circulation. 2009; 120:1640-1645.

11. UKPDS ENGINE. Available at: http://www.dtu.ox.ac.uk/riskengine.

12. AMERICAN DIABETES ASSOCIATION. Screening for Diabetes (Position Statement). Diabetes Care. 2010; 25 (Suppl. 1):S21-S24.

13. AMERICAN DIABETES ASSOCIATION. Standards of Medical Care in Diabetes-2014 (Position Statement). Diabetes Care. January 2014; 37(Suppl. 1):S14-S80.

14. JENTZSCH A. M., BACHMANN H, Improved analysis of malondialdehyde in human body fluids. Free Radic Biol Med. 1996; 20(2):251-256.

15. FESTI D, SCHIUMERINI R, MARZI L, DI BIASE AR, MANDOLESI D, MONTRONE L, SCAIOLI E, BONATO G, MARCHESINI-REGGIANI G, COLECHIA A. Review article: the diagnosis of non-alcoholic fatty liver disease - availability and accuracy of non-invasive methods. Aliment Pharmacol Ther. 2013 Feb; 37(4):392-400.

16. YOUNOSSI ZM, JARRAR M, NUGENT C, et al. A novel diagnostic biomarker panel for obesity-related non-alcoholic steatohepatitis (NASH). Obes Surg. 2008; 18:1430-1437.

17. GRIGORESCU M, CRISAN D, RADU C, GRIGORESCU MD, SPARCHEZ Z, SERBAN A. A novel pathophysiological-based panel of biomarkers for the diagnosis of non-alcoholic steatohepatitis. J of Physiol and Pharm. 2012; 63(4):347-353.

18. KHOV N, SHARMA A and RILEY TR. Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014 Jun 14; 20(22):6821-6825.

19. DALLE-DONNE I, ROSSI R, GIUSTARINI D, MILZANI A, COLOMBO R. Protein carbonyl groups as biomarkers of oxidative stress. Clinica Chimica Acta. 2003; 329(1-2):23-38.

20. ECHOUFFO-TCHEUGUI JB, SARGEANT LA, PREVOST AT, WILLIAMS KM, BARLING RS, BUTLER R, FANSHAWE T, KINMONTH AL, WAREHAM NJ, GRIFFIN SJ. How much might cardiovascular disease risk be reduced by intensive therapy in people with screen-detected diabetes? Diabet Med. 2008; 25(12):1433-1439.

21. WU YT, CHIEN CL, WANG SY, YANG WS, WU YW. Gender differences in myocardial perfusion defect in asymptomatic postmenopausal women and men with and without diabetes mellitus. J Women Health. 2013; 22(5):439-444.

22. GAMBINO R, MUSSO G, CASSADER M. Redox balance in the pathogenesis of nonalcoholic fatty liver disease: mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2011; 15(5):1325-1365.

23. ROMBOUTS K, MARRA F. Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis. Dig Dis. 2010; 28:229-235.

Journal Information

Cited By

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 171 171 22
PDF Downloads 88 88 7