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Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease

  • Nephrology - Original Paper
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Abstract

Purpose

Adiponectin may be beneficial in incipient chronic kidney disease by antagonizing oxidative stress. We evaluated adiponectin, malondialdehyde (MDA), and superoxide dismutase (SOD), in type 2 diabetes mellitus patients (T2DP) with and without incipient nephropathy.

Methods

T2DP with glomerular filtration rate (GFR) >30 ml/min were compared with 20 healthy controls. Clinical and laboratory evaluations, levels of MDA (fluorimetric thiobarbituric test), SOD (cytochrome reduction method) and adiponectin (ELISA) were obtained.

Results

Sixty-four patients (GFR 91.44 ± 38.50 ml/min, urinary albumin-to-creatinine ratio [UACR] 20.81 [4.64–72.88 mg/g]) were included. MDA was higher in T2DP than in controls: 3.97 (2.43–4.59) versus 1.35 (1.16–1.81) nmol/ml, p < 0.0001. MDA correlated with glycated hemoglobin (r = 0.40, p = 0.001), adiponectin (r = −0.28, p = 0.03), systolic blood pressure (r = −0.28, p = 0.03) and SOD (r = −0.35, p = 0.005); adiponectin (p = 0.01) and glycated hemoglobin (p = 0.02) remained significant predictors of MDA in multiple regression analysis. SOD was negatively correlated with glycemia (r = −0.71, p < 0.0001) and glycated hemoglobin (r = −0.5, p < 0.0001). When patients were divided according to a ROC-derived adiponectin cutoff of 8.9 µg/ml, patients with higher adiponectin had lower MDA, [2.55 (2.35–3.60) vs. 4.10 (2.89–5.31) nmol/ml, p = 0.005] but similar SOD levels. In T2DP with nephropathy (GFR < 60 ml/min or UACR > 30 mg/g), the correlation of adiponectin with MDA was stronger, (r = −0.51, p = 0.004) confirmed in multiple regression analysis (p = 0.03). Adiponectin was not correlated with MDA, and SOD was inversely related to MDA in patients without nephropathy.

Conclusion

Adiponectin is a significant predictor of MDA in early diabetic nephropathy, whereas SOD strongly depends only on glycemic control and is not directly related to adiponectin.

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References

  1. Li S, Shin HJ, Ding EL, van Dam RM (2009) Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 302:179–188

    Article  CAS  PubMed  Google Scholar 

  2. Chandran M, Phillips SA, Ciaraldi T, Henry RR (2003) Adiponectin: more than just another fat cell hormone? Diabetes Care 26:2442–2450

    Article  CAS  PubMed  Google Scholar 

  3. Hopkins TA, Ouchi N, Shibata R, Walsh K (2007) Adiponectin actions in the cardiovascular system. Cardiovasc Res 74:11–18

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Guebre-Egziabher F, Bernhard J, Funahashi T, Hadj-Aissa A, Fouque D (2005) Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function. Nephrol Dial Transplant 20:129–134

    Article  CAS  PubMed  Google Scholar 

  5. Komaba H, Igaki N, Goto S, Yokota K, Doi H, Takemoto t et al (2006) Increased serum high-molecular-weight complex of adiponectin in type 2 diabetic patients with impaired renal function. Am J Nephrol 26:476–482

    Article  CAS  PubMed  Google Scholar 

  6. Sweiss N, Sharma K (2014) Adiponectin effects on the kidney. Best Pract Res Clin Endocrinol Metab 28:71–79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Christou GA, Kiortsis DN (2014) The role of adiponectin in renal physiology and development of albuminuria. J Endocrinol 221:49–61

    Article  Google Scholar 

  8. Ohashi K, Iwatani H, Kihara S, Nakagawa Y, Komura N, Fujita K et al (2007) Exacerbation of albuminuria and renal fibrosis in subtotal renal ablation model of adiponectin-knockout mice. Arterioscler Thromb Vasc Biol 27:1910–1917

    Article  CAS  PubMed  Google Scholar 

  9. Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR et al (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Investig 118:1645–1656

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Lin J, Hu FB, Curhan G (2007) Serum adiponectin and renal dysfunction in men with type 2 diabetes. Diabetes Care 30:239–244

    Article  CAS  PubMed  Google Scholar 

  11. Kacso IM, Bondor CI, Kacso G (2012) Plasma adiponectin is related to the progression of kidney disease in type 2 diabetes patients. Scand J Clin Lab Investig 72:333–339

    Article  CAS  Google Scholar 

  12. Sharma K (2011) Obesity, oxidative stress, and fibrosis in chronic kidney disease. Kidney Int Suppl 4:113–117

    Article  Google Scholar 

  13. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y et al (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig 114:1752–1761

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Cui R, Gao M, Qu S, Liu D (2014) Overexpression of superoxide dismutase 3 gene blocks high-fat diet-induced obesity, fatty liver and insulin resistance. Gene Ther 21:840–848

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Tavafi M (2013) Diabetic nephropathy and antioxidants. J Nephropathol 2:20–27

    Article  PubMed Central  PubMed  Google Scholar 

  16. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  17. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 16:461–470

    Article  Google Scholar 

  18. Pippenger CE, Browne RW, Armstrong D (1993) Regulatory antioxidant enzymes. In: Armstrong D (ed) Methods in molecular biology, vol 108: free radicals and antioxidant protocols, 1st edn. Humana Press, Totowa, pp 299–311

    Google Scholar 

  19. Diaconu R, Macarie A, Orasan R (2014) Analysis of oxidative stress in sun-exposed and unexposed skin. Int J Bioflux Soc 6:153–157

    CAS  Google Scholar 

  20. Sankhla M, Sharma TK, Mathur K, Rathor JS, Butolia V, Gadhok AK et al (2012) Relationship of oxidative stress with obesity and its role in obesity induced metabolic syndrome. Clin Lab 58:385–392

    CAS  PubMed  Google Scholar 

  21. El-Mesallamy HO, Hamdy NM, Salman TM, Mahmoud S (2011) Adiponectin and E-selectin concentrations in relation to inflammation in obese type 2 diabetic patients with coronary heart disease(s). Minerva Endocrinol 36:163–170

    CAS  PubMed  Google Scholar 

  22. Vatansever E, Surmen-Gur E, Ursavas A, Karadag M (2011) Obstructive sleep apnea causes oxidative damage to plasma lipids and proteins and decreases adiponectin levels. Sleep Breath 15:275–282

    Article  PubMed  Google Scholar 

  23. Takahashi R, Imamura A, Yoshikane M, Suzuki M, Cheng XW, Numaguchi Y et al (2009) Circulating malondialdehyde-modified low-density lipoprotein is strongly associated with very small low-density lipoprotein cholesterol concentrations in healthy men. Clin Chim Acta 399:74–78

    Article  CAS  PubMed  Google Scholar 

  24. Wang X, Pu H, Ma C, Jiang T, Wei Q, Zhang C et al (2014) Adiponectin abates atherosclerosis by reducing oxidative stress. Med Sci Monit 20:1792–1800

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Song W, Huo T, Guo F, Wang H, Wei H, Yang Q et al (2013) Globular adiponectin elicits neuroprotection by inhibiting NADPH oxidase-mediated oxidative damage in ischemic stroke. Neuroscience 248:136–144

    Article  CAS  PubMed  Google Scholar 

  26. Yao R, Zhou Y, He Y, Jiang Y, Liu P, Ye L et al (2015) Adiponectin protects against paraquat-induced lung injury by attenuating oxidative/nitrative stress. Exp Ther Med 9:131–136

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Hou N, Huang N, Han F, Zhao J, Liu X, Sun X (2014) Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in early streptozotocin-induced type 2 diabetic rats. Int Urol Nephrol 46:2045–2051

    Article  CAS  PubMed  Google Scholar 

  28. Choi R, Kim BH, Naowaboot J, Lee MY, Hyun MR, Cho EJ et al (2011) Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes. Exp Mol Med 43(676–6):83

    Google Scholar 

  29. Kim HJ, Vaziri ND, Norris K, An WS, Quiroz Y, Rodriguez-Iturbe B (2010) High-calorie diet with moderate protein restriction prevents cachexia and ameliorates oxidative stress, inflammation and proteinuria in experimental chronic kidney disease. Clin Exp Nephrol 14:536–547

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Johnson DW, Armstrong K, Campbell SB, Mudge DW, Hawley CM, Coombes JS et al (2007) Metabolic syndrome in severe chronic kidney disease: prevalence, predictors, prognostic significance and effects of risk factor modification. Nephrology 12:391–398

    Article  CAS  PubMed  Google Scholar 

  31. Lim PS, Chen SL, Wu MY, Hu CY, Wu TK (2007) Association of plasma adiponectin levels with oxidative stress in hemodialysis patients. Blood Purif 25:362–369

    Article  CAS  PubMed  Google Scholar 

  32. Adachi T, Inoue M, Hara H, Maehata E, Suzuki S (2004) Relationship of plasma extracellular-superoxide dismutase level with insulin resistance in type 2 diabetic patients. J Endocrinol 181:413–417

    Article  CAS  PubMed  Google Scholar 

  33. Li X, Li MR, Guo ZX (2012) Effects of adiponectin on oxidative stress and apoptosis in human cardiac myocytes cultured with high glucose. Chin Med J 125:4209–4213

    CAS  PubMed  Google Scholar 

  34. Fukushima J, Kamada Y, Matsumoto H, Yoshida Y, Ezaki H, Takemura T et al (2009) Adiponectin prevents progression of steatohepatitis in mice by regulating oxidative stress and Kupffer cell phenotype polarization. Hepatol Res 39:724–738

    Article  CAS  PubMed  Google Scholar 

  35. Chetboun M, Abitbol G, Rozenberg K, Rozenfeld H, Deutsch A, Sampson SR et al (2012) Maintenance of redox state and pancreatic beta-cell function: role of leptin and adiponectin. J Cell Biochem 113:1966–1976

    Article  CAS  PubMed  Google Scholar 

  36. Krautbauer S, Eisinger K, Lupke M, Wanninger J, Ruemmele P, Hader Y et al (2013) Manganese superoxide dismutase is reduced in the liver of male but not female humans and rodents with non-alcoholic fatty liver disease. Exp Mol Pathol 95:330–335

    Article  CAS  PubMed  Google Scholar 

  37. Bauer S, Wanninger J, Neumeier M, Wurm S, Weigert J, Kopp A et al (2011) Elevated free fatty acids and impaired adiponectin bioactivity contribute to reduced SOD2 protein in monocytes of type 2 diabetes patients. Exp Mol Pathol 90:101–106

    Article  CAS  PubMed  Google Scholar 

  38. Zeng L, Tang WJ, Yin JJ, Zhou BJ (2014) Signal transductions and nonalcoholic fatty liver: a mini-review. Int J Clin Exp Med 7:1624–1631

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by a Grant, CNCSIS- Capacitati – Modul III 750/2014. Cosmina-Ioana Bondor is a fellow of POSDRU Grant No. 159/1.5/S/138776, grant with title: “Model colaborativ institutional pentru translatarea cercetarii stiintifice biomedicale in practica clinica – TRANSCENT.”

Conflict of interest

None.

Ethical standard

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Authors and Affiliations

  1. Department of Informatics and Biostatistics, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 6 Pasteur Street, 400349, Cluj-Napoca, Romania

    Cosmina Ioana Bondor & Crina Claudia Rusu

  2. Department of Nephrology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania

    Alina Ramona Potra, Diana Moldovan, Mariana Ciorba Pop, Dan Stefan Vladutiu & Ina Maria Kacso

  3. Department of Physiology, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj, 3-5 Clinicilor Street, 400006, Cluj-Napoca, Romania

    Adriana Muresan

Authors
  1. Cosmina Ioana Bondor
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  2. Alina Ramona Potra
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  3. Diana Moldovan
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  4. Crina Claudia Rusu
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  7. Dan Stefan Vladutiu
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  8. Ina Maria Kacso
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Correspondence to Ina Maria Kacso.

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Bondor, C.I., Potra, A.R., Moldovan, D. et al. Relationship of adiponectin to markers of oxidative stress in type 2 diabetic patients: influence of incipient diabetes-associated kidney disease. Int Urol Nephrol 47, 1173–1180 (2015). https://doi.org/10.1007/s11255-015-1004-2

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  • DOI: https://doi.org/10.1007/s11255-015-1004-2

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