Serum Nitric Oxide and Sialic Acid: Possible Biochemical Markers for Progression of Diabetic Nephropathy
This study was designed to investigate the role of serum nitric oxide and sialic acid in the development of diabetic nephropathy as disease marker. Total 210 diabetic patients (age and sex matched) were selected followed by informed consent and divided into four groups (70 each) as I: control; II: diabetic; III: diabetic hypertensive; IV: diabetic nephropathy. The blood samples of all subjects were collected and analyzed for serum nitric oxide, sialic acid, fasting blood glucose, serum urea, creatinine, HbA1c and GFR. The BMI, systolic and diastolic blood pressures, blood glucose, HbA1c and serum sialic acid levels were high (p<0.01) in group II as compared to control subjects. The higher levels (p<0.01) of BMI, systolic and diastolic blood pressures, blood glucose, HbA1c, serum urea, creatinine and sialic acid were observed in group III and IV as compared to controls. Significantly low levels of GFR and serum nitric oxide (p<0.01) were observed in group III and IV as compared to controls. Results indicated that serum nitric oxide and sialic acid are the major biochemical indicators for micro and macrovascular complications of diabetes such as hypertension and nephropathy. These should be taken into account during screening procedures regarding identifications of the diabetic patients to get them rid of progressive renal impairment to ESRD.
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 S. M. Shahid, and T. Mahboob. Electrolytes and Na-K-ATPase: potential risk factors for the development of diabetic nephropathy. Pak J Pharm Sci., vol. 21, pp. 172-179, 2008.
 J. Omer, J. Shan, D. R. Varma, and S. Mulay. Augmentation of diabetesassociated renal hyperfiltration and nitric oxide production by pregnancy in rats. J Endocrinol., vol. 161, pp. 15-23, 1999.
 P. E. James, D. Lang, T. Tufnell-Barret, A. B. Milsom, and M. P. Frenneaux. Vasorelaxation by red blood cells and impairment in diabetes. Circ Res., vol. 94, pp. 976, 2004.
 A. C. Pflueger, T. C. Larson, S. Hagl, and F. G. Knox. Role of nitric oxide in intrarenal hemodynamics in experimental diabetes mellitus in rats. Am J Physiol Regul Integr Comp Physiol., vol. 277, pp. R725- R733, 1999.
 J. Lockhart, S. Larson, and F. G. Knox. Perfusion pressure and volume status determine the microvascular response of the rat kidney to Nmonomethyl- L-arginine. Circ Res., vol. 75, pp. 829-835, 1994.
 R. Zats, and G. de Nucci. Effects of acute nitric oxide inhibition on rat glomerular microcirculation. Am J Physiol., vol. 30, pp. F360-F363, 1991.
 K. Ohishio, and P. K. Carmines. Superoxide dismutase restores the influence of nitric oxide on renal arterioles in diabetes mellitus. J Am Soc Nephrol., vol. 5, pp. 1559-1566, 1995.
 C. Walder, and C. Thiemermann, and J. Vane. The involvement of endothelium-derived relaxing factor in the regulation of renal cortical blood flow in the rat. Br J Pharmacol., vol. 102, pp. 967-973, 1991.
 M. A. Crook, J. C. Pickup, P. J. Lumb, F. Georgino, D. J. Webb, and J. H. Fuller. Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes. Diabetes Care, vol. 24, pp. 316-322, 2001.
 M. Sriharan, A. J. Reichelt, M. R. Opperman, B. B. Duncan, S. S. Mengue, M. A. Crook, and M. I. Schmidt. Total sialic acid and associated elements of the metabolic syndrome in women with and without previous gestational diabetes. Diabetes Care, vol. 25, pp. 1331- 1335, 2002.
 M. Gavella, V. Lipovac, A. Car, M. Vucic, L. Sokolic, and R. Rakos. Serum sialic acid in subjects with impaired glucose tolerance and in newly diagnosed type 2 diabetic patients. Acta Diabetol., vol. 40, pp. 95- 100, 2003.
 M A. Crook, L. Goldsmith, P. Ameerally, P. Lumb, N. Singh, J. Miell, and D. Russell-Jones. Serum sialic acid, a possible cardiovascular risk factor is not increased in Fijian Melanesians with impaired glucose tolerance or impaired fasting glucose. Ann Clin Biochem., vol. 39, pp. 606-608, 2002.
 J. Spunda, M. Neumann, D. Bartaskova, and M. Kvapil. Serum levels of sialic acid in patients with diabetes mellitus in relation to the incidence of late complications. Cas Lek Cesk., vol. 135, pp. 723-725, 1996.
 World Health Organization (WHO). Prevalence of diabetes mellitus: report of a WHO study group; 1994 (WHO Technical Report Series No. 884) Geneva.
 G. L. Bakris, M. Williams, L. Dworkin, W. J. Elliot, M. Epstein, R. Toto, K. Tuttle, J. Douglas, W. Hsueh, and J. Sowers. Preserving renal function in adults with hypertension and diabetes: a consensus approach, National Kidney Foundation Hypertension and Diabetes Executive Committee Working Group. Am J Kidney Dis., vol. 36, pp. 646-661, 2000.
 A. K. Smarason, K. G. Allman, D. Young, and C. W. Redman. Elevated levels of serum nitrate, a stable end product of nitric oxide in women with preeclampsia. Br J Obstet Gynaecol., vol. 104, pp. 538-543, 1997.
 M. Crook. The determination of serum or plasma sialic acid. Clin Biochem., vol. 26, pp. 31-37, 1997.
 A. S. Levey, T. Greene, J. W. Kusek, and M. S. Group. A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol., vol. 11, A0828, 2000.
 M. S. Goligorsky, J. Chen, and S. Brodsky. Endothelial cell dysfunction leading to diabetic nephropathy: focus on nitric oxide. Hypertension, vol. 37, pp. 744-748, 2001.
 R. Komers, J. N. Lindsley, T. T. Oyama, K. M. Allison, and S. Anderson. Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes. Am J Physiol Renal Physiol., vol. 279, pp. F573-F583, 2000.
 T. Michel, and O. Feron. Nitric oxide synthases: which, where, how and why? J Clin Invest., vol. 100, pp. 2146-2152, 1997.
 S. Vallejo, J. Angulo, C. Peiro, J. Nevado, A. Sanchez-Ferrer, R. Petidier, C. F. Sanchez-Ferrer, and L. Rodriguez-Manas. Highly glycated oxyhemoglobin impairs nitric oxide relaxations in human mesenteric microvessels. Diabetologia, vol. 43, pp. 83-90, 2000.
 M. Crook, K. Cartwright, P. Lumb, and A. Worsley. Serum sialic acid in young type 1 diabetic patients. Diabetes Res Clin Pract., vol. 47, pp. 119-122, 2000.
 G. Linderberg, G. Eklund, B. Gullberg, L. Rastam, M. Plater, C. Ionescue-Tirgouiste, A. Nuber, G. Pozza, and J. D. Ward. Serum sialic acid concentration and cardiovascular mortality. BMJ, vol. 302, pp. 143- 146, 1991.
 J. C. Pickup, M. B. Mattock, G. D. Chusney, and D. Burt. NIDDM as a disease of the innate immune system: association of acute phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia, vol. 40, pp. 1286-1292, 1997.
 H. Boumann, and J. Gauldie. The acute phase response. Immunol Today, vol. 15, pp. 74-80, 1994.
 A. Mantovani, and F. Bussolino. Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today., vol. 18, pp. 231-240, 1997.
 M. L. Caramori, P. Fioretto, and M. Mauer. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes, vol. 49, pp. 1399-1408, 2000.
 H. Yokoyama, J. S. Jensen, B. Myrup, E. R. Mathiesen, B. Ronn, and T. Decken. Raised serum sialic acid concentration precedes onset of microalbuminuria in IDDM. Diabetes Care, vol. 19, pp. 435-440, 1996.