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.
[1] 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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] 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.
[8] 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.
[9] 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.
[10] 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.
[11] 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.
[12] 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.
[13] 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.
[14] World Health Organization (WHO). Prevalence of diabetes mellitus:
report of a WHO study group; 1994 (WHO Technical Report Series No.
884) Geneva.
[15] 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.
[16] 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.
[17] M. Crook. The determination of serum or plasma sialic acid. Clin
Biochem., vol. 26, pp. 31-37, 1997.
[18] 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.
[19] 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.
[20] 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.
[21] T. Michel, and O. Feron. Nitric oxide synthases: which, where, how and
why? J Clin Invest., vol. 100, pp. 2146-2152, 1997.
[22] 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.
[23] 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.
[24] 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.
[25] 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.
[26] H. Boumann, and J. Gauldie. The acute phase response. Immunol Today,
vol. 15, pp. 74-80, 1994.
[27] 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.
[28] 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.
[29] 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.
[1] 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.
[2] 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.
[3] 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.
[4] 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.
[5] 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.
[6] 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.
[7] 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.
[8] 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.
[9] 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.
[10] 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.
[11] 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.
[12] 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.
[13] 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.
[14] World Health Organization (WHO). Prevalence of diabetes mellitus:
report of a WHO study group; 1994 (WHO Technical Report Series No.
884) Geneva.
[15] 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.
[16] 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.
[17] M. Crook. The determination of serum or plasma sialic acid. Clin
Biochem., vol. 26, pp. 31-37, 1997.
[18] 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.
[19] 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.
[20] 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.
[21] T. Michel, and O. Feron. Nitric oxide synthases: which, where, how and
why? J Clin Invest., vol. 100, pp. 2146-2152, 1997.
[22] 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.
[23] 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.
[24] 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.
[25] 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.
[26] H. Boumann, and J. Gauldie. The acute phase response. Immunol Today,
vol. 15, pp. 74-80, 1994.
[27] 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.
[28] 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.
[29] 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.
@article{"International Journal of Biological, Life and Agricultural Sciences:61173", author = "Syed M. Shahid and Rozeena Shaikh and Syeda N. Nawab and Shah A. Qader and Abid Azhar and Tabassum Mahboob", title = "Serum Nitric Oxide and Sialic Acid: Possible Biochemical Markers for Progression of Diabetic Nephropathy", abstract = "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", keywords = "Diabetic nephropathy, hypertension, nitric oxide, sialic acid.", volume = "4", number = "10", pages = "756-4", }
