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Diagnostic value of nitric oxide, lipoprotein(a), and malondialdehyde levels in the peripheral venous and cavernous blood of diabetics with erectile dysfunction

International Journal of Impotence Research volume 18, pages 544–549 (2006)Cite this article

Abstract

Diabetes mellitus (DM) is the single most common cause of erectile dysfunction (ED) seen in clinical practice. Evaluation of penile arterial insufficiency in diabetic patients currently entails expensive and invasive testing. We assessed the diagnostic value of certain peripheral and cavernous blood markers as predictors of penile arterial insufficiency in diabetic men with ED. This study was conducted on a total of 51 subjects in three groups: 26 impotent diabetics, 15 psychogenic impotent men and 10 normal age matched control males. All subjects underwent standard ED evaluation including estimation of postprandial blood sugar and serum lipid profile. Peripheral venous levels of nitric oxide (NO), lipoprotein(a) (LP(a)), malondialdehyde (MDA) and glycosylated hemoglobin (HbA1c) were obtained in all subjects. Patients in the two impotent groups underwent additional measurement of NO, LP(a) and MDA levels in cavernous blood. They also underwent intracavernosal injection (ICI) of a trimix (papaverine, prostaglandin E1 and phentolamine mixture) and pharmaco-penile duplex ultrasonography (PPDU). Compared to patients in the psychogenic group, diabetic men had significantly lower erectile response to ICI (P<0.001), lower peak systolic velocity (PSV) (P<0.001), and smaller increase in cavernosal artery diameter (CAD) (P<0.001). Peripheral and cavernous levels of both LP(a) and MDA were higher in the diabetic group as compared to the psychogenic ED group (P<0.001), while the values of peripheral venous and cavernous NO were lower (P<0.001) in the diabetic men. Comparison of biochemical marker assays with the PPDU results showed a significant negative correlation between both venous and cavernous LP(a) and MDA levels on the one hand, and PSV, and the percentage of CAD increase on the other. At the same time, peripheral and cavernous NO levels had a significant positive correlation with the same parameters. Lipoprotein(a), MDA and NO levels were better predictors of low PSV than HbA1c, cholesterol or triglyceride levels. The finding of high levels of LP(a) and MDA with low levels of NO in the peripheral and cavernous venous blood of diabetic men with ED correlates strongly with severity of ED as measured by PPDU. This provides a rationale for further studies of biochemical markers as a surrogate for traditional invasive testing in the diagnosis of penile arterial insufficiency.

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References

  1. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB . Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151 (1): 54–61.

    Article  CAS  PubMed  Google Scholar 

  2. Rosen RC, Wing R, Schneider S, Gendrano 3rd N . Epidemiology of erectile dysfunction: the role of medical comorbidities and lifestyle factors. Urol Clin North Am 2005; 32: 403–417.

    Article  PubMed  Google Scholar 

  3. Brown JS, Wessells H, Chancellor MB, Howards SS, Stamm WE, Stapleton AE et al. Urologic complications of diabetes. Diab Care 2005; 28: 177–185.

    Article  Google Scholar 

  4. Minhas S, Earley I . Diabetic impotence. In: Culley CC, Roger SK, Irwin G (eds). Textbook of Erectile Dysfunction, 1st edn. Isis Medical Media Ltd: New York, London, Barcelona, 1999, Chapter 47, pp. 541–544.

    Google Scholar 

  5. Solomon H, Man JW, Jackson G . Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator. Heart 2003; 89: 251–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G . Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987; 84: 9265–9269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lue TF . Erectile dysfunction. N Engl J Med 2000; 342: 1802–1813.

    Article  CAS  PubMed  Google Scholar 

  8. Bivalacqua TJ, Hellstrom WJ, Kadowitz PJ, Champion HC . Increased expression of arginase II in human diabetic corpus cavernosum: in diabetic-associated erectile dysfunction. Biochem Biophys Res Commun 2001; 283: 923–927.

    Article  CAS  PubMed  Google Scholar 

  9. Andersson KE, Hedlund P, Alm P . Sympathetic pathways and adrenergic innervation of the penis. Int J Impot Res 2000; 12 (Suppl 1): S5–S12.

    Article  CAS  PubMed  Google Scholar 

  10. Danesh J, Collins R, Peto R . Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 2000; 102: 1082–1085.

    Article  CAS  PubMed  Google Scholar 

  11. De Young L, Yu D, Bateman RM, Brock GB . Oxidative stress and antioxidant therapy: their impact in diabetes-associated erectile dysfunction. J Androl 2004; 25: 830–836.

    Article  PubMed  Google Scholar 

  12. Agarwal A, Nandipati KC, Sharma RK, Zippe CD, Raina R . Role of oxidative stress in pathophysiology of erectile dysfunction. J Androl 2005; [E-pub ahead of print].

  13. Piconi L, Quagliaro L, Ceriello A . Oxidative stress in diabetes. Clin Chem Lab Med 2003; 41: 1144–1149.

    Article  CAS  PubMed  Google Scholar 

  14. Griesmacher A, Kindhauser M, Andert SE, Schreiner W, Toma C, Knoebl P et al. Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus. Am J Med 1995; 98: 469–475.

    Article  CAS  PubMed  Google Scholar 

  15. Little RR, England JD, Wiedmeyer HM, McKenzie EM, Mitra R, Erhart PM et al. Interlaboratory standardization of glycated hemoglobin determinations. Clin Chem 1986; 32: 358–360.

    CAS  PubMed  Google Scholar 

  16. Schmidt HH, Walter U . NO at work. Cell 1994; 78: 919–925.

    Article  CAS  PubMed  Google Scholar 

  17. Matsumoto M, Wakasugi H, Ibayashi H . Serum vitamin E, lipid peroxide and glutathione peroxidase in patients with chronic pancreatitis. Clin Chim Acta 1981; 110: 121–125.

    Article  CAS  PubMed  Google Scholar 

  18. Gries A, Nimpf J, Nimpf M, Wurm H, Kostner GM . Free and Apo B-associated Lpa-specific protein in human serum. Clin Chim Acta 1987; 164: 93–100.

    Article  CAS  PubMed  Google Scholar 

  19. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC . Enzymatic determination of total serum cholesterol. Clin Chem 1974; 20: 470–475.

    CAS  PubMed  Google Scholar 

  20. Warnick GR, Benderson J, Albers JJ . Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein cholesterol. Clin Chem 1982; 28: 1379–1388.

    CAS  PubMed  Google Scholar 

  21. Wahlefeld AW . Triglycerides determination after enzymatic hydrolysis.In: Bergmyere HW (ed). Methods of enzymatic analysis. Academic Press: New York, 1974, p. 18.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  23. Atahan O, Kayigil O, Hizel N, Metin A . Is apolipoprotein-(a) an important indicator of vasculogenic erectile dysfunction? Int Urol Nephrol 1998; 30: 185–191.

    Article  CAS  PubMed  Google Scholar 

  24. Robinson LQ, Woodcock JP, Stephenson TP . Results of investigation of impotence in patients with overt or probable neuropathy. Br J Urol 1987; 60: 583–587.

    Article  CAS  PubMed  Google Scholar 

  25. Musicki B, Kramer MF, Becker RE, Burnett AL . Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction. Proc Natl Acad Sci USA 2005; 102: 11870–11875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Azadzoi KM, Kim N, Brown ML, Goldstein I, Cohen RA, Saenz de Tejada I . Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. J Urol 1992; 147: 220–225.

    Article  CAS  PubMed  Google Scholar 

  27. Hamed EA, Meki AR, Gaafar AA, Hamed SA . Role of some vasoactive mediators in patients with erectile dysfunction: their relationship with angiotensin-converting enzyme and growth hormone. Int J Impot Res 2003; 15: 418–425.

    Article  CAS  PubMed  Google Scholar 

  28. Seftel AD, Vaziri ND, Ni Z, Razmjouei K, Fogarty J, Hampel N et al. Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS. Urology 1997; 50: 1016–1026.

    Article  CAS  PubMed  Google Scholar 

  29. Cartledge JJ, Eardley I, Morrison JF . Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in ageing and diabetes. BJU Int 2001; 87: 394–401.

    Article  CAS  PubMed  Google Scholar 

  30. Sullivan ME, Mumtaz FH, Dashwood MR, Thompson CS, Naseem KM, Bruckdorfer KR et al. Enhanced relaxation of diabetic rabbit cavernosal smooth muscle in response to nitric oxide: potential relevance to erectile dysfunction. Int J Impot Res 2002; 14: 523–532.

    Article  CAS  PubMed  Google Scholar 

  31. Sozmen B, Delen Y, Girgin FK, Sozmen EY . Catalase and paraoxonase in hypertensive type 2 diabetes mellitus: correlation with glycemic control. Clin Biochem 1999; 32: 423–427.

    Article  CAS  PubMed  Google Scholar 

  32. Khan MA, Thompson CS, Jeremy JY, Mumtaz FH, Mikhailidis P, Morgan RJ . The effect of superoxide dismutase on nitric oxide-mediated and electrical field-stimulated diabetic rabbit cavernosal smooth muscle relaxation. BJU Int 2001; 87: 98–103.

    Article  CAS  PubMed  Google Scholar 

  33. De Young L, Yu D, Freeman D, Brock GB . Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model. Int J Impot Res 2003; 15: 347–354.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Biochemistry Department, Mansoura University, Mansoura, Egypt

    M A El-Latif & T E Gouda

  2. Department of Urology, University of Illinois, Chicago, IL, USA

    A A Makhlouf & C S Niederberger

  3. Andrology Department, Mansoura University, Mansoura, Egypt

    Y M Moustafa & S M Elhanbly

Authors
  1. M A El-Latif
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  2. A A Makhlouf
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  3. Y M Moustafa
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  4. T E Gouda
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  5. C S Niederberger
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  6. S M Elhanbly
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Correspondence to C S Niederberger.

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El-Latif, M., Makhlouf, A., Moustafa, Y. et al. Diagnostic value of nitric oxide, lipoprotein(a), and malondialdehyde levels in the peripheral venous and cavernous blood of diabetics with erectile dysfunction. Int J Impot Res 18, 544–549 (2006). https://doi.org/10.1038/sj.ijir.3901473

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