Skip to main content
SpringerLink
Log in

Relationship of PON1 activity and hsCRP concentration with disease status in patients with type 2 diabetes mellitus with and without retinopathy

  • Original Article
  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

The purpose of this study was to determine paraoxonase-I activity (PON 1), lipid profile and hsCRP in type 2 diabetic patients with and without retinopathy who had the same duration of the disease (10 years), to determine the correlations among these parameters and to compare these values with those measured in normal control subjects. Fifty four subjects (mean age 58 ± 7 years, men / women 25/29) with type 2 diabetes (T2DM) with proliferative diabetic retinopathy (PDR) (N = 25) and without retinopathy (nonDR) (N = 29) were included in the study. Twenty four healthy subjects were selected as control group (61 ± 6 years, men / women 10/14). Paraoxonase and arylesterase activities were measured spectrophotometrically. The DM + PDR group had lower paraoxonase activity (199 ± 39 vs. 258 ± 60 U/L, P < 0.05) and higher hsCRP (5.8 ± 4.9 vs. 3.2 ± 1.1 mg/L, P < 0.05) than the healthy control group. In patients with DM, paraoxonase activity was positively associated with HDL cholesterol and negatively associated with serum glucose, total cholesterol, and LDL cholesterol. Although hsCRP was elevated and paraoxonase was decreased in type 2 diabetic patients, a link between oxidation and inflammation and the development of diabetic retinopathy remains unexplored.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. American Academy of Ophthalmology. 2003. Diabetic retinopathy preferred practice pattern. Accessed Nov 24, 2006.

  2. Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, et al. Retinopathy in diabetes. Diabetes Care. 2004;27 Suppl 1:84–7.

    Article  Google Scholar 

  3. Lyons TJ, Li W, Wells-Knecht MC, Jokl R. Toxicity of mildly modified low-density lipoproteins to cultured retinal capillary endothelial cells and pericytes. Diabetes. 1994;43:1090–5.

    Article  PubMed  CAS  Google Scholar 

  4. Garner A. Histopathology of diabetic retinopathy in man. Eye. 1993;7:250–3.

    Article  PubMed  Google Scholar 

  5. Lyons TJ, Baynes JW, Patrick JS, Colwell JA, Lopes-Virella MF. Glycosylation of low density lipoprotein in patients with type 1 (insulin-dependent) diabetes: correlations with other parameters of glycaemic control. Diabetologia. 1986;29:685–9.

    Article  PubMed  CAS  Google Scholar 

  6. Pennathur S, Heinecke JW. Mechanisms for oxidative stress in diabetic cardiovascular disease. Antioxid Redox Signal. 2007;9:955–69.

    Article  PubMed  CAS  Google Scholar 

  7. Ravandi A, Kuksis A, Shaikh NA. Glucosylated glycerophosphoethanolamines are the major LDL glycation products and increase LDL susceptibility to oxidation: evidence of their presence in atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000;20:467–77.

    Article  PubMed  CAS  Google Scholar 

  8. Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low densıty lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999;26:892–904.

    Article  PubMed  CAS  Google Scholar 

  9. Durrington P, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol. 2001;21:473.

    Article  PubMed  CAS  Google Scholar 

  10. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett. 1991;286:152–4.

    Article  PubMed  CAS  Google Scholar 

  11. Aviram M. Introduction to the serial review on paraoxonases, oxidative stress, and cardiovascular diseases. Free Radic Biol Med. 2004;37:1301–3.

    Article  PubMed  CAS  Google Scholar 

  12. Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN. Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett. 1998;423:57–60.

    Article  PubMed  CAS  Google Scholar 

  13. Pennathur S, Heinecke JW. Mechanisms of oxidative stress in diabetes: implications for the pathogenesis of vascular disease and antioxidant therapy. Front Biosci. 2004;9:565–74.

    Article  PubMed  CAS  Google Scholar 

  14. Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci. 2004;107:435–47.

    Article  PubMed  CAS  Google Scholar 

  15. Hofer SE, Bennetts B, Chan AK, Holloway B, Karschimkus C, Jenkins AJ, et al. Association between PON 1 polymorphisms, PON activity and diabetes complications. J Diabetes Complications. 2006;20:322–8.

    Article  PubMed  Google Scholar 

  16. van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S. Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm. 2010;15.

  17. Pino SC, Kruger AJ, Bortell R. The role of innate immune pathways in type 1 diabetes pathogenesis. Curr Opin Endocrinol Diabetes Obes. 2010;17:126–30.

    Article  PubMed  CAS  Google Scholar 

  18. Ikeda Y, Suehiro T, Inoue M, Nakauchi Y, Morita T, Arii K, et al. Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus. Metabolism. 1998;47:598–602.

    Article  PubMed  CAS  Google Scholar 

  19. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33:S62–S69

  20. Mackness B, Durrinton P, McElduff P, Yarnell J, Azam N, Watt M, et al. Low paraoxonase activity predicts coronary events in the Caerphilly prospective Study. Circulation. 2003;107:2775–9.

    Article  PubMed  CAS  Google Scholar 

  21. Haagen L, Brock A. A new automated method for phenotyping arylesterase (E.C.3.1.1.2.) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. Eur J Clin Chem Clim Biochem. 1992;30:391–5.

    CAS  Google Scholar 

  22. Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004;18:1450–2.

    PubMed  CAS  Google Scholar 

  23. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA. 2001;286:327–34.

    Article  PubMed  CAS  Google Scholar 

  24. Chase HP, Cooper S, Osberg I, Stene LC, Barriga K, Norris J, et al. Elevated C-reactive protein levels in the development of type 1 diabetes. Diabetes. 2004;53:2569–73.

    Article  PubMed  CAS  Google Scholar 

  25. Ford ES. Body mass index, diabetes, and C-reactive protein among U.S. adults. Diabetes Care. 1999;22:1971–7.

    Article  PubMed  CAS  Google Scholar 

  26. van Hecke MV, Dekker JM, Nijpels G, Moll AC, Heine RJ, Bouter LM, et al. Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study. Diabetologia. 2005;48:1300–6.

    Article  PubMed  CAS  Google Scholar 

  27. Mackness B, McElduff P, Mackness MI. The paraoxonase-2-310 polymorphism is associated with microvascular complications in diabetes mellitus. J Intern Med. 2005;258:363–8.

    Article  PubMed  CAS  Google Scholar 

  28. Koch M, Hering S, Barth C, Ehren M, Enderle MD, Pfohl M. Paraoxonase 1 192 Gln/Arg gene polymorphism and cerebrovascular disease interaction with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2001;109:141–5.

    Article  PubMed  CAS  Google Scholar 

  29. Deakin SP, James RW. Genetic and environmental factors for modulating serum concentrations and activities of the antioxidant enzyme paraoxonase. Clin Sci. 2004;107:435–7.

    Article  PubMed  CAS  Google Scholar 

  30. Lee CT, Rowley K, Jenkins AJ, O’Dea K, Itsiopoulos C, Stoney RM, et al. Paraoxonase activity in Greek migrants and Anglo-Celtic persons in the Melbourne collaborative cohort survey: relationship to dietary markers. Eur J Nutr. 2005;44:223–30.

    Article  PubMed  CAS  Google Scholar 

  31. Agachan B, Yilmaz H, Karaali Z, Isbir T. Paraoxonase 55 and 192 polymorphisms and its relationship to serum paraoxonase activity and serum lipids in Turkish patients with non-insulin-dependent diabetes. Cell Biochem Funct. 2004;22:163–8.

    Article  PubMed  CAS  Google Scholar 

  32. Sozmen B, Delen Y, Girgin FK, Sozmen EY. Catalase and paraoxonase in hypertensive subjects with Type 2 diabetes mellitus: correlation with glycaemic control. Clin Biochem. 1999;32:423–7.

    Article  PubMed  CAS  Google Scholar 

  33. Kopprasch S, Pietzsch J, Kuhlisch E, Graessler J. Lack of association between serum paraoxonase-1 activities and increased oxidised low density lipoprotein levels in impaired glucose tolerance and newly diagnosed diabetes. J Clin Endocrinol Metab. 2003;288:1711–6.

    Article  Google Scholar 

  34. Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P. Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr. 2002;75:767–72.

    PubMed  CAS  Google Scholar 

  35. Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Insulin as an anti-inflammatory and antiatherogenic modulator. J Am Coll Cardiol. 2009;3:S14–20.

    Article  Google Scholar 

  36. Kalogerakis G, Baker AM, Christov S, Rowley KG, Dwyer K, Winterbourn C, et al. Oxidative stress and high-density lipoprotein function in Type I diabetes and end-stage renal disease. Clin Sci. 2005;108:497–506.

    Article  PubMed  CAS  Google Scholar 

  37. Baynes JW. Chemical modification of proteins by lipids in diabetes. Clin Chem Lab Med. 2003;41:1159–65.

    Article  PubMed  CAS  Google Scholar 

  38. Hedrick CC, Thorpe SR, Fu MX, Harper CM, Yoo J, Kim SM, et al. Glycation impairs high-density lipoprotein function. Diabetologia. 2000;43:312–20.

    Article  PubMed  CAS  Google Scholar 

  39. Nevin DN, Zambon A, Furlong CE, Richter RJ, Humbert R, Hokanson JE, et al. Paraoxonase genotypes, lipoprotein lipase activity and HDL. Arterioscler Thromb Vasc Biol. 1996;16:1243–9.

    Article  PubMed  CAS  Google Scholar 

  40. Sozmen EY, Sozmen B, Delen Y, Onat T. Catalase/superoxide dismutase (SOD) and catalase/paraoxonase (PON) ratios may implicate poor glycemic control. Arch Med Res. 2001;32:283–7.

    Article  PubMed  CAS  Google Scholar 

  41. Abbott CA, Mackness MI, Kumar S, Boulton AJ, Durrington PN. Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol. 1995;15:1812–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflicting interests.

Author information

Authors and Affiliations

  1. Clinical Laboratory Section, Sevket Yilmaz Education and Research Hospital, Bursa, 16330, Turkey

    Yasemin Ustündag Budak

  2. Ophthalmology Section, Sevket Yilmaz Education and Research Hospital, Bursa, 16330, Turkey

    Müberra Akdogan

  3. Clinical Laboratory Section, Bursa Yuksek Ihtisas Education and Research Hospital, Bursa, 16330, Turkey

    Kagan Huysal

Authors
  1. Yasemin Ustündag Budak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Müberra Akdogan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kagan Huysal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasemin Ustündag Budak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Budak, Y.U., Akdogan, M. & Huysal, K. Relationship of PON1 activity and hsCRP concentration with disease status in patients with type 2 diabetes mellitus with and without retinopathy. Int J Diabetes Dev Ctries 33, 40–45 (2013). https://doi.org/10.1007/s13410-012-0103-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-012-0103-1

Keywords

Search

Navigation