Acta Diabetologica

, Volume 45, Issue 1, pp 41–46

Oxidative stress in non-insulin-dependent diabetes mellitus (NIDDM) patients

Original Article

Abstract

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Proteins and lipids are among the prime targets for oxidative stress. In the present study, the oxidative stress was evaluated in 55 diabetic patients and 40 healthy subjects by measuring the levels of protein oxidation, lipid peroxidation and some enzymatic and nonenzymatic antioxidants. The oxidative products of protein (PCG) and lipid peroxidation (MDA) and nitric oxide levels in plasma of NIDDM patients were significantly increased. However, the levels of enzymatic (GPx, SOD, catalase in RBC) and nonenzymatic (β-carotene, retinol, vitamin C & E and uric acid) antioxidants of RBC showed a significant decrease in NIDDM patients compared to normal subjects. Serum protein analysis by polyacrylamide gel electrophoresis (PAGE) showed the significant difference in the ceruloplasmin, transferrin, albumin, retinal binding protein, etc. in diabetic patients compared to healthy controls. In conclusion, the results suggest that increased protein oxidation, lipid peroxidation and NO levels, decreases the levels of enzymatic and nonenzymatic antioxidants and playing a major role in diabetic complications.

Keywords

Diabetes Non-insulin-dependent diabetes mellitus (NIDDM) Protein oxidation Lipid oxidation Antioxidant status Oxidative stress 

References

  1. 1.
    American Diabetic Association (2006) Guidelines. Standards of medical care in Diabetes. Diabetes Care 28:S4–S36CrossRefGoogle Scholar
  2. 2.
    Ashour M, Salem S, Hassaneen H, EL-Gadban H, Elwan N, Awad A, TK Basu (1999) Antioxidant status and insulin dependent diabetes mellitus (IDDM). J Clin Biochem Nutr 26:99–107Google Scholar
  3. 3.
    Atamer Y, Kocyigit Y, Atamer A, Mete N, Canoruc N, Toprak G (1998) Alterations of erythrocyte and plasma lipid peroxides as well as antioxidant mechanism in patients with type II diabetes mellitus (NIDDM). Tr J Med Sci 28:143–148Google Scholar
  4. 4.
    Beutler E (1984). Red cell metabolism. A manual of biochemical methods, 3 edn. Grune and Stratton, New YorkGoogle Scholar
  5. 5.
    Bulger EM, Maier VR (2001) Antioxidants in critical illness. Arch Surg 136:1201–1206PubMedCrossRefGoogle Scholar
  6. 6.
    Bucala R, Cerami A (1992) Advanced glycosylation: chemistry, biology and implications for diabetes and aging. Adv Pharm 23:1–4Google Scholar
  7. 7.
    Condell RA, Tappel Al (1983) Evidence for suitability of glutathione peroxidase as protective enzyme: studies of oxidative damage, resoration and proteolysis. Arch Biochem Biophys 223:407–416PubMedCrossRefGoogle Scholar
  8. 8.
    Cigremis Y, Kose M, Ozgurlu F, Turkoz Y, Egri M (2003) The investigation of erythrocyte SOD, Cat and GPX antioxidant enzyme level in pateints with type 2 diabetes mellitus. GU J Sci 16:239–244Google Scholar
  9. 9.
    Dominguez C, Ruiz E, Gussinye M, Carrascisa A (1998) Oxidative stress at onset and in early stages of type I diabetes in children and adolescents. Diabetes Care 21:1736–1742PubMedCrossRefGoogle Scholar
  10. 10.
    Doumas BT, Watson WA, Biggs HG (1971) Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chem Acta 31:87CrossRefGoogle Scholar
  11. 11.
    Diamon M, Susa S, Yamatani K, Manaka H, Hama K, Kimura M, Ohnuma H, Kato T (1997) Hyperglycemia is a factor for an increase in serum ceruloplasmin in type II diabetes. Diabetes Care 21(9):1525–1528CrossRefGoogle Scholar
  12. 12.
    Elliott TG, Cockcroft JR, Groop PH, Viberti GC, Ritter JM (1993) Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria. Clin Sci 85:687–693PubMedGoogle Scholar
  13. 13.
    Faure P, Benhamou PY, Perard A, Halimi S, Roussel AM (1995) Lipid peroxidationin insulin dependent diabetic patients with early retina degenerative lesions: Effects of an oral zinc supplementation. Eur J Clin Nutr 49:282–288PubMedGoogle Scholar
  14. 14.
    Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121PubMedCrossRefGoogle Scholar
  15. 15.
    Frei B (1994) Reactive oxygen species and antioxidant vitamins mechanisms of action. Am J Med 97:5S–13SPubMedCrossRefGoogle Scholar
  16. 16.
    Forbes JM, Yee LT, Thallas V, Lassila M, Candido R, Jandeleit-Dahm KA, Thomas MC, Burns WC, Deemer EK, Thorpe SM, Cooper ME, Allen TJ (2004) Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes 53: 1813–1823PubMedCrossRefGoogle Scholar
  17. 17.
    Garibaldi S, Aragno I, Odetti P, Marianari UM (1994) Relationships between protein carbonyls, retinol, and tocopherols levels in human plasma. Biochem Mol Biol Int 34:729–736PubMedGoogle Scholar
  18. 18.
    Halliwell B (1997) Antioxidants and human disease: a general introduction. Nutr Rev 55:S44–S52PubMedCrossRefGoogle Scholar
  19. 19.
    Hirano K, Tohru O, Hiromi O, Mayo H, Masashi H, Hiroshi T (2005) Identification of apo- and holo-forms of ceruloplasmin in patients with Wilson’s disease using native polyacrylamide gel electrophoresis. Clin Biochem 38:9–12PubMedCrossRefGoogle Scholar
  20. 20.
    Hartnett ME, Stratton RD, Browne Rw, Rosner BA, Lanham RJ, Armstrong D (2000) Serum markers of oxidative stress and severity of diabetic retinopathy. Diabetes Care 23(2):234–240PubMedCrossRefGoogle Scholar
  21. 21.
    Irshad M, Chaudhuri PS (2002) Oxidant-antioxidant system: role and significance in human body. Indian J Exp Biol 40:1233–1239PubMedGoogle Scholar
  22. 22.
    Jacob RA (1995) The integrated antioxidant system. Nutr Res 15:755–766CrossRefGoogle Scholar
  23. 23.
    Jain SK, Mc Vie R (1994) Effect of glycemic control race (white vs black) and duration of diabetes on reduced glutathion content in erythrocytes of diabetic patients. Metabolism 43:306–309PubMedCrossRefGoogle Scholar
  24. 24.
    Kalousova M, Skrha J, Zima T (2002) Advanced glycation end products and advanced oxidation protein products in-patients with diabetes mellitus. Physio Res 51:597–604Google Scholar
  25. 25.
    Kawamura N, Ookawara T, Suzuki K, Konishi K, Mino M, Taniguchi NC (1992) Increased glycated Cu, Zn superoxide dismutase levels in erythrocytes of patients with insulin dependent diabetes mellitus. J Clin Endocrinol Metab 74:1352–1354PubMedCrossRefGoogle Scholar
  26. 26.
    Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head bacteriophage T4. Nature 227:680–685PubMedCrossRefGoogle Scholar
  27. 27.
    Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadman ER (1990) Determination of carbonyl content in oxidatively modified proteins. In: Pecker L,Glazer AN (eds) Methods in enzymology, vol 186. Academic, New York, 464–478Google Scholar
  28. 28.
    Lenzen S, Drinkgem J, Tiedge M (1996) Low antioxidant enzyme gene expression in pancreatic islets compared with variouws other mouse tissues. Free Rad Bio Med 20:463–466CrossRefGoogle Scholar
  29. 29.
    Marjani A (2005) Plasma lipid peroxidation zinc and erythrocyte Cu-Zn superoxide dismutase enzyme activity in patients with type 2 diabetes mellitus in Gorgan city (south east of the Caspian Sea). Internet J Endocrinol 2(1). http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijen/vol2n1/lipid.xml
  30. 30.
    Matteucci E, Giampietro O (2000) Oxidation stress in families of type I diabetic patients. Diabetic Care 23(8):1182–1186CrossRefGoogle Scholar
  31. 31.
    Miller NJ, Evans CR, Davies MJ, Gopinathan V, Milner A (1993) A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 8:407–412Google Scholar
  32. 32.
    Maxwell SRJ, Thompson H, Sandler D, Leguen C, Baxter MA, Thorpe GHG, Jones A, Barnett AH (1997) Antioxidant status in patients with uncomplicated insulin dependent and non-insulin dependent diabetes mellitus. Eur J Clin Invest 27:484–490PubMedCrossRefGoogle Scholar
  33. 33.
    Memisogullari R, Taysi S, Bakan E, Capoglu I (2003) Antioxidant status and lipid peroxidation in type 2 diabetes mellitus. Cell Biochem Funct 21(3):291–296PubMedCrossRefGoogle Scholar
  34. 34.
    Mooradian AD, Failla M, Hoogwerf B, Maryniuk M, Wylie-Roset J (1994) Selected vitamins and minerals in diabetes. Diabetes Care 5:464–478Google Scholar
  35. 35.
    Moshage H, Kok B, Huizenga JR, Jansen PLM (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 41(6):892–896PubMedGoogle Scholar
  36. 36.
    Matkovics A (2003) An overview of free radical research. Acta Biol Szegediensis 47(1–4):93–97Google Scholar
  37. 37.
    Mohan IK, Das UN (1997) Oxidant stress, antioxidants and nitric oxide in NIDDM. Med Sci Res 25:55–57Google Scholar
  38. 38.
    Nourooz-Zadeh J, Rahimi A, Tajaddini-Sarmadi J, Tritschler H, Rosen P, Halliwel B, Betteridge DJ (1997) Relationships between plasma measures of oxidative stress and metabolic control in NIDDM. Diabetologica 40:647–663CrossRefGoogle Scholar
  39. 39.
    Ndahimana J, Dorchy H, Vertongen EC (1996) Erythrocyte and plasma antioxidant activity in type I diabetes mellitus. Press Med 25:188–192Google Scholar
  40. 40.
    Polidori MC, Mecocci P, Stahl W, Parente B, Cecchetti R, Cherubini A, Cao P, Sies H, Senin U (2000) Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 16:15–19PubMedCrossRefGoogle Scholar
  41. 41.
    Palanduz S, Ademoglu E, Gokkusu C, Tamer S (2001) Plasma antioxidants and type 2 diabetes mellitus. Res Commun Mol Pathol Pharmacol 109:309–318PubMedGoogle Scholar
  42. 42.
    Pasaoglu H, Sancak B, Bukan N (2004) Lipid peroxidation and resistance to oxidation in patients with type 2 diabetes mellitus. Tohoku J Exp Med 203 (3):211–218PubMedCrossRefGoogle Scholar
  43. 43.
    Ramaswamy G, Rao VR, Kumaraswamy SV, Anantha N (1996) Serum vitamins status in oral leucoplakias—a preliminary study. Eur J Cancer B Oral Oncol 32:120CrossRefGoogle Scholar
  44. 44.
    Renu AK, Timothy SK, Engerman RL (1997) Abnormalities of retinol metabolism in diabetes or experimental galactosemia. Free Rad Biol Med 22(4):587–592Google Scholar
  45. 45.
    Raghuramulu N, Madhavan Nair K, Kalyanasundaram S (2003) A manual of laboratory techniques. National Institute of Nutrition, HyderabadGoogle Scholar
  46. 46.
    Seghieri G, Di Simplicio P, De Giorgio LA, Anichini R, Alberti L, Franconi F (2000) Relationship between metabolic glycaemic control and platelet contenty of glutathione and its related enzymes, in insulin-dependent diabetes mellitus. Clin Chem Acta 299(1–2):109–117CrossRefGoogle Scholar
  47. 47.
    Sinclair AJ, Lunec J, Girling AJ, Barnett AH (1992) Modulators of free radical activity in diabetes mellitus: role of ascorbic acid. EXS 62:342–352PubMedGoogle Scholar
  48. 48.
    Sharma A, Kharb S, Chugh SN, Kakkar R, Singh GP (2000) Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients. Metabolism 49:160–162PubMedCrossRefGoogle Scholar
  49. 49.
    Skrha J, Hodinar A, Kvosnicka J, Hilgertova J (1996) Relationship of oxidative stress and fibrinolysis in diabetes mellitus. Diabet Med 13:800–805PubMedCrossRefGoogle Scholar
  50. 50.
    Scheuer H, Gwinner W, Hohbach J, Grone EF, Brandes RP, Malle E, Olbricht CJ, Walli AK, Grone HJ (2000) Oxidant stress in hyperlipidemia-induced renal damage. Am J Physiol Renal Physiol 278:63–74Google Scholar
  51. 51.
    Steindl P, Ferenci P, Dienes HP (1997) Wilson’s disease in patients presenting with liver disease: a diagnostic challenge. Gastroenterolgy 113:212–218CrossRefGoogle Scholar
  52. 52.
    Sundaram RK, Bhaskar A, Vijayalingam S, Viswanathan M, Mohan R, Shanmugasundaram KR (1996) Antioxidant status and lipid peroxidation in type 2 diabetes mellitus with and without complications. Clin Sci 90:255–260PubMedGoogle Scholar
  53. 53.
    Tsai EC, Hirseh IB, Brunzell JD, Chail A (1994) Reduced plasma peroxy radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes 43:1010–1014PubMedCrossRefGoogle Scholar
  54. 54.
    Turk HM, Sevinc A, Camci C, Cigli A, Buyukberber S, Savli H, Bayraktar N (2002) Plasma lipid peroxidation products and antioxidant enzyme activities in patients with type 2 diabetes mellitus. Acta Diabetol 39:117–122PubMedCrossRefGoogle Scholar
  55. 55.
    Telci A, Cakatay U, Kayali R, Erdogan C, Orhan Y, Sivas A, Akcay T (2000) Oxidative protein damage in plasma of type 2 diabetic patients. Horm Metab Res 32(1):40–43PubMedCrossRefGoogle Scholar
  56. 56.
    Tiwari AK (2004) Antioxidants: new generation therapeutic base for treatment of polygenic disorders. Curr Sci 86(8):1092–1102Google Scholar
  57. 57.
    Tian J, Chen JH, Li Q, He Q, Lin WQ (2005) Lipid peroxidation in IgA nephropathy and the effect of lipo-prostaglandin E1. J Nephrol 18:243–248PubMedGoogle Scholar
  58. 58.
    Vanizor B, Orem A, Karahan SC et al (2001) Decreased nitric oxide end-products its relationship with high density lipoprotein and oxidative stress in people with type 2 diabetes without complications. Diabetes Res Clin Prac 54:33–39CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of BiotechnologySri Krishnadevaraya UniversityAnantapurIndia
  2. 2.Department of BiochemistryBLDEAs: Shri B M Patil Medical CollegeBijapurIndia

Personalised recommendations