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International Ophthalmology

, Volume 38, Issue 6, pp 2445–2450 | Cite as

Elevated serum fetuin-A levels are associated with grades of retinopathy in type 2 diabetic patients

  • Ahu YilmazEmail author
  • Tolga Yilmaz
  • Murat Gunay
Original Paper
  • 80 Downloads

Abstract

Purpose

Fetuin-A is a physiological inhibitor of insulin receptor tyrosine kinase and thus associated with insulin resistance, metabolic syndrome, and an increased risk for type 2 diabetes mellitus (T2DM). This study aims to investigate the possible relation between the serum fetuin-A levels and the stages of diabetic retinopathy (DR) in patients with T2DM.

Methods

This prospective study included 82 patients with T2DM and 19 age- and gender-matched healthy controls (HCs) (group 1). Diabetic patients were subclassified into three groups according to ocular findings: without DR (group 2; n = 26); non-proliferative DR (group 3; n = 29), and proliferative DR (group 4; n = 27). Serum fetuin-A levels were determined by a spectrophotometric technique using an immulite chemiluminescent immunometric assay. The data were analyzed using a Mann–Whitney U test, and the results were expressed as mean ± standard deviation.

Results

Mean fetuin-A values were 256.4 ± 21.3 μg/ml in group 1, 263.5 ± 24.2 μg/ml in group 2, 282.2 ± 31.1 μg/ml in group 3, and 296.3 ± 26.2 μg/ml in group 4. Group 2 had higher mean fetuin-A level compared with group 1, but the difference was not statistically significant (p > 0.05). Serum fetuin-A levels were significantly higher in groups 3 and 4 compared with HCs (both p < 0.05). Compared with group 2, both DR groups had higher fetuin-A levels with a significant difference (both p < 0.05); and patients with proliferative DR had significantly higher serum fetuin-A levels compared with non-proliferative DR (p < 0.05). The mean serum fetuin-A levels increased with the stage of DR, and the highest levels were found in patients with proliferative DR.

Conclusion

Our findings suggest an association between fetuin-A levels and DR stage. In diabetic patients, the risk of retinopathy development increases with higher fetuin-A values. Fetuin-A may play an important role in the pathophysiology and progression of DR.

Keywords

Fetuin-A Type 2 diabetes mellitus Diabetic retinopathy Insulin resistance 

Notes

Compliance with ethical standards

Conflict of interests

The authors declare that there are no conflicts of interest.

References

  1. 1.
    Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053CrossRefGoogle Scholar
  2. 2.
    Rodrigues TC, Pecis M, Azevedo MJ, Gross JL (2005) Blood pressure homeostasis and microvascular complications in diabetic patients. Arq Bras Endocrinol Metabol 49:882–890CrossRefGoogle Scholar
  3. 3.
    Fong DS, Aiello LP, Ferris FL, Klein R (2004) Diabetic retinopathy. Diabetes Care 27:2540–2553CrossRefGoogle Scholar
  4. 4.
    El-Asrar AM (2012) Role of inflammation in the pathogenesis of diabetic retinopathy. Middle East Afr J Ophthalmol 19:70–74CrossRefGoogle Scholar
  5. 5.
    El-Asrar AM, Siddiquei MM, Nawaz MI, Hertogh GD, Mohammad G, Alam K et al (2016) Coexpression of heparanase activity, cathepsin L, tissue factor, tissue factor pathway inhibitor, and MMP-9 in proliferative diabetic retinopathy. Mol Vis 30:424–435Google Scholar
  6. 6.
    Abu El-Asrar AM, Nawaz MI, De Hertogh G, Alam K, Siddiquei MM, Van den Eynde K et al (2014) S100A4 is upregulated in proliferative diabetic retinopathy and correlates with markers of angiogenesis and fibrogenesis. Mol Vis 10:1209–1224Google Scholar
  7. 7.
    El-Asrar AM, Nawaz MI, Kangave D, Siddiquei MM, Geboes K (2013) Angiogenic and vasculogenic factors in the vitreous from patients with proliferative diabetic retinopathy. J Diabetes Res 10:1155–1164Google Scholar
  8. 8.
    Młyńczak JO, Mroczek JA (2008) Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes—srole of the inflammatory–immune process in the pathogenesis of proliferative diabetic retinopathy. Graefe’s Arch Clin Exp Ophthalmol 246:1665–1670CrossRefGoogle Scholar
  9. 9.
    Denecke B, Graber S, Schafer C, Heiss A, Woltje M, Jahnen-Dechent W (2003) Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J 376:135–145CrossRefGoogle Scholar
  10. 10.
    Mathews ST, Chellam N, Srinivas PR, Cintron VJ, Leon MA, Goustin AS et al (2000) α2-HSG, a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Mol Cell Endocrinol 164:87–98CrossRefGoogle Scholar
  11. 11.
    Lorant DP, Hoellerl F, Grujicic M, Brix JM, Hoellerl F, Schernthaner G et al (2011) Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes Care 34:156–161CrossRefGoogle Scholar
  12. 12.
    Ix JH, Sharma K (2010) Mechanism linking obesity, chronic kidney disease and fatty liver disease: the roles of fetuin-A, adiponectin and AMPK. J Am Soc Nephrol 21:406–412CrossRefGoogle Scholar
  13. 13.
    Kalabay L, Jakab L, Prohászka Z, Fust G, Benko Z, Telegdy L et al (2002) Human fetuin/α2HS-glycoprotein level as a novel indicator of liver cell function and short term mortality in patients with liver cirrhosis and liver cancer. Eur J Gastroenterol Hepatolol 14:389–394CrossRefGoogle Scholar
  14. 14.
    Kalabay L, Szalay F, Nemesanszky E, Telegdy L, Jakab L, Romies L (1997) Decreased serum α2-HS-glycoprotein concentration in patients with primary biliary cirrhosis. J Hepatol 26:1426–1427CrossRefGoogle Scholar
  15. 15.
    Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Krober SM et al (2006) α2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 29:853–857CrossRefGoogle Scholar
  16. 16.
    Jung CH, Kim BY, Kim CH, Kang SK, Jung SH, Mok JO (2013) Associations of serum fetuin-A levels with insulin resistance and vascular complications in patients with type 2 diabetes. Diabetes Vasc Dis Res 10:459–467CrossRefGoogle Scholar
  17. 17.
    Zhao ZW, Lin CG, Wu LZ, Luo YK, Fan L, Dong XF et al (2013) Serum fetuin-A levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes. Biomarkers 18:160–164CrossRefGoogle Scholar
  18. 18.
    Wilkinson CP, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M et al (2003) Global Diabetic Retinopathy Project Group: proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 110:1677–1682CrossRefGoogle Scholar
  19. 19.
    Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS et al (2002) Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 51:2450–2458CrossRefGoogle Scholar
  20. 20.
    Stefan N, Fritsche A, Weikert C, Boeing H, Joost HG, Häring HU et al (2008) Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 57:2762–2767CrossRefGoogle Scholar
  21. 21.
    Ix JH, Wassel CL, Kanaya AM, Vittinghoff E, Johnson KC, Koster A et al (2008) Fetuin-A and incident type 2 diabetes mellitus in older persons. JAMA 300:182–188CrossRefGoogle Scholar
  22. 22.
    Zhou Z, Ju H, Sun M, Chen H, Ji H, Jiang D et al (2015) Serum fetuin-A concentrations are positively associated with serum VEGF levels in patients with newly diagnosed type 2 diabetes. Endocr J 62:879–885CrossRefGoogle Scholar
  23. 23.
    Zhao C, Hou J, Wang S, Jiang R (2015) Relation of serum and vitreus concentrations of fetuin-A with diabetic retinopathy. Med Sci Monit 25:1839–1842Google Scholar
  24. 24.
    Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H et al (2006) Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care 29:468CrossRefGoogle Scholar
  25. 25.
    Ostenson CG (2001) The pathophysiology of type 2 diabetes mellitus: an overview. Acta Physiol Scand 171:241–247CrossRefGoogle Scholar
  26. 26.
    Joussen AM, Fauser S, Krohne TU, Lemmen KD, Lang GE, Kirchhof B (2003) Diabetic retinopathy: pathophysiology and therapy of hypoxia-induced inflammation. Ophthalmologe 100:363–370CrossRefGoogle Scholar
  27. 27.
    Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Haring HU et al (2008) Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS ONE 12:1765CrossRefGoogle Scholar
  28. 28.
    Siegel-Axel DI, Ullrich S, Stefan N, Rittig K, Gerst F, Klingler C et al (2014) Fetuin-A influences vascular cell growth and production of proinflammatory and angiogenic proteins by human perivascular fat cells. Diabetologia 57:1057–1066CrossRefGoogle Scholar
  29. 29.
    Bento CF, Fernandes R, Matafome P, Sena C, Seica R, Pereira P (2010) Methylglyoxal-induced imbalance in the ratio of vascular endothelial growth factor to angiopoietin 2 secreted by retinal pigment epithelial cells leads to endothelial dysfunction. Exp Physiol 95:955–970CrossRefGoogle Scholar
  30. 30.
    Roos M, Oikonomou D, von Eynatten M, Luppa PB, Heemann U, Lutz J et al (2010) Associations of fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy. Cardiovasc Diabetol 7:48–55CrossRefGoogle Scholar
  31. 31.
    Emoto M, Mori K, Lee E, Kawano N, Yamazaki Y, Tsuchikura S et al (2010) Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus. Metabolism 59:873–878CrossRefGoogle Scholar
  32. 32.
    Bilgir O, Kebapcilar L, Bilgir F, Bozkaya G, Yildiz Y, Pinar P et al (2010) Decreased serum fetuin-A levels are associated with coronary artery diseases. Intern Med 49:1281–1285CrossRefGoogle Scholar
  33. 33.
    Miettinen H, Haffner SM, Lehto S, Rönnemaa T, Pyörälà K, Laakso M (1996) Retinopathy predicts coronary heart disease events in NIDDM patients. Diabetes Care 19:1445–1448CrossRefGoogle Scholar
  34. 34.
    Targher G, Bertolini L, Zenari L, Lippi G, Pichiri I, Zoppini G et al (2008) Diabetic retinopathy is associated with an increased incidence of cardiovascular events in Type 2 diabetic patients. Diabetes Med 25:45–50CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  1. 1.Department of OphthalmologyBagcilar Education and Research HospitalIstanbulTurkey
  2. 2.Department of OphthalmologyBeyoglu Eye Education and Research HospitalIstanbulTurkey
  3. 3.Department of BiochemistryMengucek Gazi Education and Research HospitalErzincanTurkey

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