Title: Role of Elevated Serum Sialic Acid in the Progression of both Diabetic Retinopathy and Diabetic Nephropathy

Authors: Soher A.Mohammed Ismail, Hadeer Bakeer, Mustafa Abdel Aziz M., Iman A. Fahmy, Mohamed El Hefni, Shimaa Nabil, Safyea Mohamed Hussien, Leqaa A. Moemen, Mona A. Abdel Hamid, Margeret A. Aziz

 DOI:  http://dx.doi.org/10.18535/jmscr/v3i11.49

Abstract

Purpose: The purpose of this study was mainly to determine the relationship between total serum sialic acid and occurrence and progression of diabetic retinopathy and diabetic nephropathy in diabetic patients.

Materials and Methods: The study included 60 subjects, their ages ranged between 45-60 year;most of diabetic patients had controlled blood pressure. These subjects were divided into the following groups:

Control group: involved 15 healthy subjects. Clinical and laboratory investigation were performed for each to exclude the presence of diabetes mellitus or any associated disease.

Group (1): involved15 diabetic patients without retinopathy

Group (2): involved 15 diabetic patients with non-proliferative diabetic retinopathy (NPDR).

Group (3): involved 15 diabetic patients with proliferative diabetic retinopathy (PDR).

Urine and fasting blood samples were collected. Patients with DR were clinically examined by a specialist. The standard curve of sialic acid was drawn using Echrlich method. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c%), serum total cholesterol, serum HDL-cholesterol, serum triglycerides (STG), serum creatinine, serum urea, microalbuminuria, urine creatinine and serum c-reactive protein were estimated using LABOMED, Inc (spectro uv-vis Double Beam Pc with 8 scanning autocell uv D-3200). Serum LDL-cholesterol and urine albumin/creatinine ratiowere calculated.

Results: The study showed statistical significant increase in total serum sialic acid in all diabetic patients but the increase was more prominent in patients with proliferative DR. There were increase in fasting glucose level, glycosylated HB%, total cholesterol, triglycerides, LDL-C, serum urea, serum creatinine and urinary albumin/creatinine ratio with decrease in HDL-C in diabetic retinopathy patients ( mainly with proliferative retinopathy ), the increase was statistically significant. This increase in these parameters was parallel to this increase in total serum sialic acid but not reach to significant correlation. The statistically significant correlation was found between total serum sialic acid and both age of the patients and duration of diabetes.

Conclusion: Serum sialic acid concentrations were increased in type 2 diabetics with and without complications and this increase was strongly related to the progression of retinopathy and occurrence of nephropathy 

Keywords: sialic acid, diabetic retinopathy, diabetic nephropathy

References

1.      Yarema, K. (2006). The sialic acid pathway in human cells.Baltimore: John Hopkins University.

2.      Radhakrishnamurthy, B., Berenson, G. S., Pargaonkar, P. S., Voors, A. W., Srinivasan, S. R., Plavidal, F., Dolan, P., and DalferesJr, E. R. (1976). Serum-free and protein-bound sugars and cardiovascular complications in diabetes mellitus.Laboratory investigation; a journal of technical methods and pathology, 34(2), 159.

3.      Shvarts, L. S., and Paukman, L. I. (1971). Diabetic angiopathies and mucopolysaccharide metabolism. Problemyendokrinologii, 17(1), 37-41.

4.      Crook, M. (1993). The determination of plasma or serum sialic acid.Clinical biochemistry, 26(1), 31-38.

5.      Pickup, J. C. (2004). Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes care, 27(3), 813-823.

6.      Early Treatment Diabetic Retinopathy Study Research Group. (1991). Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. Early Treatment Diabetic Retinopathy Study Research Group report number 10. Ophthalmology, 98(5), 786-806.

7.      Sydow, G., Wittmann, W., Bender, E., and Starick, E. (1988). The sialic acid content of the serum of cattle infected with bovine leukosis virus. Archivfürexperimentelle Veterinärmedizin, 42(2), 194-197.

8.      Bolton, S., and Bon, C. (2003). Pharmaceutical Statistics: Practical and Clinical Applications, Edition Number: 4, Publisher: Taylor and Francis, Inc.

9.      Sillanaukee, P., Ponnio, M., and Jaaskelainen, I. P. (1999). Occurrence of sialic acids in healthy humans and different disorders.European journal of clinical investigation, 29(5), 413-425.

10.  Pradeepa, R., Anjana, R. M., Unnikrishnan, R., Ganesan, A., Mohan, V., and Rema, M. (2010). Risk factors for microvascular complications of diabetes among South Indian subjects with type 2 diabetes—the Chennai Urban Rural Epidemiology Study (CURES) Eye Study-5. Diabetes technology and therapeutics, 12(10), 755-761.

11.  Ford, E. S. (1999). Body mass index, diabetes, and C-reactive protein among US adults.Diabetes care, 22(12), 1971-1977.

12.  Ross, R. (1999). Atherosclerosis—an inflammatory disease.New England journal of medicine, 340(2), 115-126.

13.  Baynes, J. W., and Thorpe, S. R. (1999). Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes, 48(1), 1-9.

14.  Ola, M. S., Nawaz, M. I., Siddiquei, M. M., Al-Amro, S., and Abu El-Asrar, A. M. (2012). Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. Journal of Diabetes and its Complications, 26, 56-64.

15.  Sato, K. K., Hayashi, T., Harita, N., Yoneda, T., Nakamura, Y., Endo, G., and Kambe, H. (2009). Combined measurement of fasting plasma glucose and A1C is effective for the prediction of type 2 diabetes the Kansai Healthcare Study. Diabetes Care, 32(4), 644-646.

16.  Gillett, M. J. (2009). International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes: Diabetes Care 2009; 32 (7): 1327–1334. The Clinical Biochemist Reviews, 30(4), 197-200.

17.  Shivananda Nayak, B., and Bhaktha, G. (2005).Relationship between sialic acid and metabolic variables in Indian type 2 diabetic patients.Lipids in health and disease, 4(1), 15.

18.  Sharrett, A. R., Ballantyne, C. M., Coady, S. A., Heiss, G., Sorlie, P. D., Catellier, D., and Patsch, W. (2001). Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein (a), apolipoproteins AI and B, and HDL density subfractions the atherosclerosis risk in communities (ARIC) study. Circulation, 104(10), 1108-1113.

19.  Mendall, M. A., Patel, P., Ballam, L., Strachan, D., and Northfield, T. C. (1996). C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. British medical journal, 312(7038), 1061-1065.

20.  Erren, M., Reinecke, H., Junker, R., Fobker, M., Schulte, H., Schurek, J. O., Kropf, J., Kerber, S., Breithardt, G., Assmann, G., and Cullen, P. (1999). Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arteriosclerosis, thrombosis, and vascular biology, 19(10), 2355-2363.

21.  Fahie-Wilson, M., Mills, R., and Wilson, K. (1987). HDL cholesterol and the acute phase reaction following myocardial infarction and acute pancreatitis. Clinicachimicaacta, 167(2), 197-209.

22.  Klein, R., Klein, B. E., and Moss, S. E. (1992). Epidemiology of proliferative diabetic retinopathy.Diabetes care, 15(12), 1875-1891.

23.  El-Wakf, A. M., Abbas, M., El-Baz, A., and Mohammed, A. (2011). Role of Hypertension and Metabolic Abnormalities in the Development of Diabetic Nephropathy among Egyptian Patients with Type 2 Diabetes. Nature and Science, 9(7), 220-228.

24.  Sasso, F. C., De Nicola, L., Carbonara, O., Nasti, R., Minutolo, R., Salvatore, T., Conte, G., and Torella, R. (2006). Cardiovascular risk factors and disease management in type 2 diabetic patients with diabetic nephropathy. Diabetes Care, 29(3), 498-503.

25.  Keane, W. F., Brenner, B. M., De Zeeuw, D., Grunfeld, J. P., Mcgill, J., Mitch, W. E., Ribeiro, A. B., Shahinfar, S., Simpson, R. L., Snapinn, S. M., and Toto, R. (2003). The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney international, 63(4), 1499-1507.

26.  Chen, J. W., Gall, M. A., Yokoyama, H., Jensen, J. S., Deckert, M., and Parving, H. H. (1996). Raised serum sialic acid concentration in NIDDM patients with and without diabetic nephropathy.Diabetes care, 19(2), 130-134.

27.  Stehouwer, C. D., Henry, R. M., Dekker, J. M., Nijpels, G., Heine, R. J., and Bouter, L. M. (2004). Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: Further evidence for a link between microalbuminuria and endothelial dysfunction—The Hoorn Study. Kidney International, 66(supplement 92), S42-S44.

28.  Ritz, E. (2003). Minor renal dysfunction: an emerging independent cardiovascular risk factor. Heart, 89(9), 963-964.

29.  Festa, A., D'agostino, R., Howard, G., Mykkänen, L., Tracy, R. P., and Haffner, S. M. (2000). Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. Kidney international, 58(4), 1703-1710.

30.  Baud, L., and Ardaillou, R. (1994). Tumor necrosis factor alpha in glomerular injury. Kidney international, 45( Supplement 45), S32-S36.

31.  Klein, N. J., Shennan, G. I., Heyderman, R. S., and Levin, M. I. C. H. A. E. L. (1992). Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils Journal of cell science, 102(4), 821-832.

32.  Deckert, T., Kofoed-Enevoldsen, A., Nørgaard, K., Borch-Johnsen, K., Feldt-Rasmussen, B., and Jensen, T. (1992).Microalbuminuria: implications for micro-and macrovascular disease. Diabetes care, 15(9), 1181-1191.

33.  Murussi, M., Murussi, N., Campagnolo, N., and Silveiro, S. P. (2008). Early detection of diabetic nephropathy.ArquivosBrasileiros de Endocrinologia and Metabologia, 52(3), 442-451.

34.  Fong, D. S., Aiello, L., Gardner, T. W., King, G. L., Blankenship, G., Cavallerano, J. D., Ferris, F. L., and Klein, R. (2004). Retinopathy in diabetes.Diabetes Care, 27(suppl 1), S84-S87.

35.  Sillanaukee, P., Ponnio, M., and Jaaskelainen, I. P. (1999). Occurrence of sialic acids in healthy humans and different disorders.European journal of clinical investigation, 29(5), 413-425.

36.  Pönniö, M., Alho, H., Nikkari, S. T., Olsson, U., Rydberg, U., and Sillanaukee, P. (1999). Serum sialic acid in a random sample of the general population.Clinical chemistry, 45(10), 1842-1849.

37.  Crook, M. A., Treloar, A., Haq, M., and Tutt, P. (1994). Serum total sialic acid and acute phase proteins in elderly subjects. Clinical Chemistry and Laboratory Medicine, 32(10), 745-747.

38.  Milman, N., Graudal, N., and Andersen, H. C. (1988). Acute phase reactants in the elderly.Clinicachimicaacta, 176(1), 59-62.

39.  Fagiolo, U., Cossarizza, A., Scala, E., FanalesBelasio, E., Ortolani, C., Cozzi, E., Monti, D., Franceschi, c., and Paganelli, R. (1993). Increased cytokine production in mononuclear cells of healthy elderly people.European journal of immunology, 23(9), 2375-2378.

40.  Caswell, M., Pike, L. A., Bull, B. S., and Stuart, J. (1993). Effect of patient age on tests of the acute-phase response.Archives of pathology and laboratory medicine, 117(9), 906-910.

41.  Bruunsgaard, H., Pedersen, M., and Pedersen, B. K. (2001). Aging and proinflammatory cytokines.Current opinion in hematology, 8(3), 131-136.

Corresponding Author

Soher Abdel Wahab

Medical Biochemistry

Department Research Institute of Ophthalmology