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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 35  |  Issue : 2  |  Page : 257-263

Relationship between serum sialic acid concentration and diabetic retinopathy in Egyptian patients with type 2 diabetes mellitus


1 Endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Benha University, Banha, Egypt
2 Internal Medicine, Faculty of Medicine, Benha, University, Banha, Egypt
3 Hepatology and Tropical Medicine Research Institute, Cairo, Egypt

Date of Submission03-Feb-2018
Date of Acceptance21-Mar-2018
Date of Web Publication17-Aug-2018

Correspondence Address:
Dr. Ahmed E Mansour
Internal Medicine, Faculty of Medicine, Benha, University, Banha, 13511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bmfj.bmfj_17_18

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  Abstract 


Background Degree of diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus (DM) and one of the most common causes of blindness worldwide. Plasma sialic acid (SA) is one of the markers that has been utilized as an acute-phase response. In DR, there is a great increase in SA.
Aim We aimed in this study to shed light on the relationship between serum SA and DR in Egyptian patients with type 2 DM.
Patients and methods The patients of this study included 40 patients with type 2 DM (25 with DR and 15 without DR) as well as 10 healthy volunteers as control. A questionnaire was done to every patient including baseline characteristics, examination, laboratory investigations, and dilated fundus examination.
Results Serum SA level was found to be significantly increased in patients with type 2 DM compared with control and in diabetic patients with retinopathy compared with diabetic patients without retinopathy.
Conclusion This study showed that DR has a significant impact on serum SA level.

Keywords: diabetic retinopathy, sialic acid, type 2 diabetes mellitus


How to cite this article:
El-Sayed MS, El Badawy A, Abdelmoneim RO, Mansour AE, Khalil ME, Darwish K. Relationship between serum sialic acid concentration and diabetic retinopathy in Egyptian patients with type 2 diabetes mellitus. Benha Med J 2018;35:257-63

How to cite this URL:
El-Sayed MS, El Badawy A, Abdelmoneim RO, Mansour AE, Khalil ME, Darwish K. Relationship between serum sialic acid concentration and diabetic retinopathy in Egyptian patients with type 2 diabetes mellitus. Benha Med J [serial online] 2018 [cited 2018 Nov 19];35:257-63. Available from: http://www.bmfj.eg.net/text.asp?2018/35/2/257/239187




  Introduction Top


Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia [1]. Chronic hyperglycemia results in structural changes in the retina. Experimental evidence suggests that several molecular pathways may be implicated in the development of degree of diabetic retinopathy (DR). The prevalence of DR increases with the duration of diabetes. Additional risk factors include a lesser degree of glycemic control, the type of diabetes (historically, type 1 >2), and the presence of associated conditions such as hypertension, smoking, nephropathy, dyslipidemia, and pregnancy [2]. DM has been considered as a disease with activation of the innate immunity system, and acute-phase reactants, such as C-reactive protein and sialic acid (SA), have been proposed to be predictors of the risk of developing type 2 DM [3]. SA is a genetic term of a family of acetylated derivatives of neuraminic acid. It is an essential component of glycoproteins and glycolipids. It acts as a cofactor of many cell surface receptors, for example, insulin receptor and is positively associated with most of the serum acute phase reactants [4]. More than 50% of the total SA in serum comes from the acute-phase proteins. Free SA appears to be cleared from plasma by the kidney in a manner similar to creatinine, being filtered by the glomerulus, but not reabsorbed by the tubules. Significant elevations of total circulating SA have been documented in renal disease, diabetes, variety of central nervous system disorders, ovarian cancer, and in arthritis [5]. Serum SA level is increased in both type 1 and type 2 DM patients with microvascular complications [6]. In DR, there is a greater increase in SA due to the damage of the vascular endothelial cells and it is considered as a newly established potential risk factor for the development of DR [7].


  Patients and methods Top


This is a cross-sectional prospective study which was carried out on 25 type 2 diabetic patients with retinopathy and 15 type 2 diabetic patients without retinopathy as well as 10 healthy volunteers as control.

Study design

Thorough history taking and clinical examination were performed to every patient with special stress on age, sex, BMI, smoking state, type and duration of diabetes, medications, complications, other comorbidites. Laboratory tests were done to every patient (such as fasting and postprandial plasma glucose level, cholesterol, triglyceride (TG), hemoglobin A1c (HbA1c), serum creatinine, blood urea, estimated glomerular filtration rate, 24 h urinary albumin, serum SA level), and dilated fundus examination by an ophthalmoscope.

Statistical analysis

All collected data were tabulated and analyzed using the statistical package for the social sciences (SPSS) version 16 (SPSS Inc., Chicago, Illinois, USA) to obtain the following.

Descriptive data

Descriptive statistics were calculated for the data in the form of:
  1. Mean±SD for quantitative data.
  2. Frequency and distribution for qualitative data.


Analytical statistics

In the statistical comparison between the different groups, the significance of difference was tested using one of the following tests.
  1. Student’s t-test: used to compare the mean of two groups of quantitative data.
  2. Analysis of variance test (F value): used to compare the mean of more than two groups of quantitative data.
  3. Intergroup comparison of categorical data was performed by using Fisher’s exact test.
  4. Correlation coefficient: to find the relationship between variables.
  5. A P value of less than 0.05 was considered statistically significant while more than 0.05 was considered statistically insignificant.



  Results Top


Among the studied groups 15 (30%) were men and 35 (70%) were women with their age ranging from 49 to 65 years with a mean age of 57 years and BMI ranged from 23 to 36 kg/m2 with a mean BMI of 30.5 kg/m2. The mean value of BMI was significantly high in group B compared with group A and C ([Table 1]). There is significant increase in fasting blood glucose (FPG), post postprandial blood glucose (PPBG), HbA1c, serum cholesterol, serum TG, serum creatinine, blood urea, 24 h urinary albumin, degree of DR, and SA level in group A (patients with DR) compared with group B and C (diabetic patients without retinopathy and control) ([Table 2]). There was significant increase in FPG, PPBG, HbA1c, cholesterol, TGs, creatinine, urea, 24 h urinary albumin, degree of DR, and SA level in patients with DR (A) compared with the control group (C) ([Table 3]). There is significant increase in FPG, PPBG, HbA1c, serum cholesterol, serum TGs, and SA level in group B patients compared with group C ([Table 4]). It also shows nonsignificant difference in FPG, PPBG, HbA1c between group A and group B and also shows significant increase in serum cholesterol, serum TGs, and SA level in group A patients compared with group B ([Table 5]). [Table 6] shows the fundus examination of the study group. [Table 7] shows the highly significant correlation between the degree of DR and level of SA in the A group (diabetic patients complicated with DR). Regression analysis shows that the parameters of glycemic control (FPG, PPBG, HbA1c), 24 h urinary albumin, and SA level are considered as a significant predictor of the degree of DR ([Table 8] and [Table 9]). The parameters of glycemic control (FPG, PPBG, HbA1c) are considered as a significant predictor of SA level ([Table 10]).
Table 1 Sociodemographic and anthropometric variables and their comparison between the study groups

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Table 2 Biochemical variables and their comparison between the study groups

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Table 3 Biochemical variables and their comparison between patients with diabetic retinopathy and control group

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Table 4 Biochemical variables and their comparison between diabetic noncomplicated patients and the control group

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Table 5 Biochemical variables and their comparison between patients with diabetic retinopathy and diabetic noncomplicated patients

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Table 6 Fundus examination findings in the study groups

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Table 7 Correlation between degree of diabetic retinopathy and serum sialic acid

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Table 8 Correlation between serum sialic acid and some categories

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Table 9 Linear regression analysis for the prediction of degree of diabetic retinopathy

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Table 10 Linear regression analysis for predictors of serum sialic acid

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The table shows that there is a highly significant positive correlation between SA and glycemic control (FPG, PPS, and HbA1c), serum creatinine, serum TG, serum cholesterol, BMI, duration of D.M and degree of DR.

There is a nonsignificant correlation between SA and age of patient and age at onset of discovery of DM.

[Table 8] shows that FPG, PPBG, HbA1c, 24 h albumin, serum creatinine, and SA level are significant predictors of the level and degree of DR.{Table 8}

[Table 9] shows that FPG, PPBG, and HbA1c are significant predictors of SA level.{Table 9}


  Discussion Top


Serum SA is a marker of the acute phase response [8]. SA maintains the negative charge of renal glomerular basement membrane, which is one of the main regulators of membrane permeability. Due to increased vascular permeability there is shedding of vascular endothelial SA leading to its increased levels in circulation [9]. Diabetes is the leading cause of vision loss in patients between the ages of 20 and 74 years in industrialized nations [10]. In DR, there is a greater increase in SA due to the damage of the vascular endothelial cells and it is considered as a newly established potential risk factor for the development of DR [7]. Our study showed that diabetes has a significant impact on serum SA level. This could be inferred from the following: Serum SA level is significantly high in diabetic patients when compared with the control group (Table 4), A positive significant correlation was found between the parameters of glycemic control (FPG, PPBG, HbA1c) and SA level ([Table 8] and [Table 9]) and parameters of glycemic control (FPG, PPBG, HbA1c) are considered as a significant predictor of SA level ([Table 10]).

This results is in agreement with Divija et al. [11], who revealed a significant positive correlation between serum SA and glycated hemoglobin, FBS and post postprandial blood sugar (PPBS) in diabetic cases indicate that as SA increases, glycated hemoglobin and other parameters also increases. Subzwari and Qureshi [12] showed a significant increase of serum SA among the diabetic patients compared with the control patients. Serum and urine SA concentration increased in diabetic patients as compared with the general population, especially in type 2 diabetic patients. Poddar and Ray [13] revealed a clear cut elevation in SA levels which is evident from the data in diabetics without complications as compared with the healthy controls. Carter and Martin [14] showed significantly elevated serum TSA levels in type 2 diabetic patients without microvascular complications. In two separate studies by Kumar et al. [15] and Izumida et al. [16], it was found that serum and urine levels of SA was significantly high in diabetic patients. Englyst et al. [17] observed that serum SA concentrations were strongly associated with several risk factors like the glycemic status.

In our study, a significant positive correlation was found between serum SA level and BMI, cholesterol and TG ([Table 8] and [Table 9]). This results is in agreement with Browning et al. [18], who showed that the percentage of body fat is a predictor of fasting plasma SA. We have demonstrated that SA concentration is higher in BMI-matched groups of individuals with type 2 diabetes compared with controls. In addition, the results from this study suggest that the percentage of body fat may contribute to the higher levels of plasma SA observed in people with type 2 DM, although other factors may also be important. Ghosh et al. [19] showed a significant incremental association between SA and individual features of the metabolic syndrome, which remains significant after adjustment for BMI. Sillanaukee et al. [20] revealed a good correlation between SA and important cardiovascular risk factors such as cholesterol, low density cholesterol (LDL) and TG.

Our study showed that DR has a significant impact on serum SA level. This could be inferred from the following: serum SA levels is significantly high in DR patients when compared with the control group and with diabetic patients without retinopathy ([Table 2], [Table 3], [Table 5]). A positive significant correlation was found between SA level and DR and parameters of DN ([Table 8] and [Table 9]) and SA level is considered as a significant predictor of the degree of DR ([Table 8],[Table 9],[Table 10]).

This results is in agreement with Ghosh et al. [19] who revealed that serum SA levels were found to be significantly increased in diabetes with or without microvascular complications compared with controls. The development and severity of these complications are dependent on the duration of the disease and how well it is managed. Prospective studies have reported associations among various markers of inflammation and incidence of diabetes. Among the various pathogenic features induced by metabolic abnormalities in diabetes, oxidative stress and increased inflammatory responses appear to be some of the first detectable abnormalities. In patients with established type 2 diabetes it has been suggested that complications are associated with increased SA levels [20] compared with people without these complications. The cross-sectional analyses of the EURODIAB study showed elevated SA concentrations in type 1 diabetic patients with retinopathy (men), neuropathy (men), and albuminuria (men and women), indicating the need to explore these findings prospectively. Crook et al. [21] explained their results based on three factors leading to increased serum SA levels: shedding of SA from glycoconjugates of cell membranes, increased levels of acute-phase proteins, and increased activity or biosynthesis of neuraminidase enzyme. Serum acute-phase proteins are known to be elevated in both type 1 and type 2 DM patients [22].

Additionally, there are abnormalities in the red blood cell membrane in diabetic patients that can also lead to the release of SA and increased levels of urine and serum SA. Englyst et al. [17] revealed a significant positive correlation between serum SA and creatinine excretion, serum SA and serum creatinine levels and a statistically significant difference was observed in values of serum creatinine, serum SA, and controls. It was also observed that serum SA concentrations were strongly associated with several risk factors like renal dysfunction (creatinine) and urine albumin excretion for the development of microvascular and macrovascular complications. These markers were clinically correlated with increasing concentration of SA. It is concluded that an increase in circulating serum SA is an early manifestation of diabetic microvascular complications and serum SA levels in NIDDM are helpful in assessing the progress of disease and identifying the risk category for complications. Krishnamurthy et al. [23] showed a progressive rise in serum SA levels with the urinary albumin excretion as a marker of microvascular complications in DM and a significant positive correlation between them. Roozbeh et al. [5] revealed that the serum and urine levels of SA and neuraminidase activity were always abnormally higher in diabetic patients complicated with microvascular complication when compared with diabetic patients without complications. Yokoyama et al. [24] revealed that serum SA concentration was increased in patients with clinical diabetic microangiopathy compared with noncomplicated patients which was significantly correlated independently with serum SA. Kumar et al. [15] and Izumida et al. [16] revealed in two separate studies that there was an increase in serum and urine SA levels in diabetic patients when microangiopathy was present. They reported that serum and urine levels of SA was significantly high in diabetic patients and remained higher when the diabetes was complicated with microangiopathy. Poddar and Ray [13] showed that a clear cut elevation in SA levels is evident from the data [FBS, PPBS, HbA1c, TG, cholesterol, high density cholesterol (HDL), LDL, creatinine] in diabetics without complications as compared with healthy controls. The levels were even higher in diabetic patients with complications.

On the other hand, Tomino et al. [25] observed that the levels of SA in sera from diabetic microangiopathy patients were significantly increased, but they found no significant correlation between the levels of blood urea nitrogen (BUN), serum creatinine or proteinuria and SA. They explained their results thus. It is generally believed that SAs are composed mainly of N-acetyl neuraminic acid and are contained in the tissues, blood, mucin, and milk. Although an increase of SA in sera is observed in patients with various kinds of inflammatory diseases and cancers, this is considered to be a nonspecific phenomenon. Crook et al. [21] found that there is no significant correlation between serum total SA and patient age, serum fructosamine, diabetes duration, and blood pressure in the United Arab Emirates and in South Asia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison’s Principles of Internal Medicine 19/E (Vol. 1 & Vol. 2). McGraw-Hill Education; 2015. 269, 554.‏  Back to cited text no. 1
    
2.
Zhang X, Saaddine JP, Chou CF, Cotch MF, Cheng YJ, Geiss LS et al. Prevalence of diabetic retinopthy in united states, 2005–2008. JAMA 2010; 304:649.  Back to cited text no. 2
    
3.
Crook M. Type 2 diabetes mellitus: a disease of the innate immune system? an update. Diabet Med 2004; 21:203–207.  Back to cited text no. 3
    
4.
Varki A. Essential of glycobiology 2nd ed. New York, NY: Cold Spring Harbor Laboratory Press, Cold Spring Harbor; 2009.  Back to cited text no. 4
    
5.
Roozbeh J, Merat A, Bodagkhan F, Afshariani R, Yarmohammadi H. Significance of serum and urine neuraminidase activity and serum and urine level of sialic acid in diabetic retinopathy. Int Urol Nephrol 2011; 43:1143–1148.  Back to cited text no. 5
    
6.
Yarema K. The sialic acid pathway in human cells. Baltimore: John Hopkins University; 2006. pp. 149–152.  Back to cited text no. 6
    
7.
Prajna K, Kumar A, Rai S, Shetty SK, Rai T, Shrinidhi MB, Shashikala MD. Predictive value of serum sialic acid in type-2 diabetes mellitus and its complication (retinopathy). J Clin Diagn Res 2013; 7:2435.  Back to cited text no. 7
    
8.
Shahid SM, Mahaboob T. Clinical correlation between frequent risk factors of diabetic retinopathy and serum sialic acid. Int J Diabet Metab 2006; 14:138–142.  Back to cited text no. 8
    
9.
Mohammad JS, Muhammad TM, Ahmad M, Riaz M, Umair M. Serum sialic acid concentration and type 2 DM. Professional Med J Dec 2006; 13:508–510.  Back to cited text no. 9
    
10.
Roy MS, Janal MN. High caloric and sodium intakes as risk factors for progression of retinopathy in type 1 diabetes mellitus. Arch Ophthalmol 2010; 128:33–39.  Back to cited text no. 10
    
11.
Divija DA, Rajeshwari A, Nusrath A. Correlation of serum sialic acid with glycemic status in diabetic retinopathy. Int J Bioassays 2014; 3:1789–1793.  Back to cited text no. 11
    
12.
Subzwari J, Qureshi MA. Relationship between sialic acid and microvascular complications in type 2 diabetes mellitus. Biomedica 2012; 28:130–133.  Back to cited text no. 12
    
13.
Poddar A, Ray S. Serum sialic acid levels in diabetic subjects: a promising screening tool for microvascular & macrovascular complications in diabetes. Int J Sci Res 2015; 4.  Back to cited text no. 13
    
14.
Carter A, Martin NH. Serum sialic acid levels in health and disease. J Clin Pathol 1962; 15:69–72.  Back to cited text no. 14
    
15.
Kumar SP, Latha JM, Amarendra M, Benerji GV. A study of serum sialic acid in non insulin dependent diabetes mellitus. Indian J Basic Appl Med Res 2015; 4:612–619.  Back to cited text no. 15
    
16.
Izumida Y, Seiyama A, Maeda N. Erythrocyte aggregation: bridging by macromolecules and electrostatic repulsion by sialic acid. Biochem Biophys Acta 1991; 1067:221–226.  Back to cited text no. 16
    
17.
Englyst NA, Crook MA, Lumb P, Stears AJ, Masding MG, Wootton SA et al. Percentage of body fat and plasma glucose predict plasma sialic acid concentration in type 2 diabetes mellitus. Metabolism 2006; 55:1165–1170.  Back to cited text no. 17
    
18.
Browning LM, Jebb SA, Mishra GD, Cooke JH, O’Connell MA, Crook MA, Krebs JD. Elevated sialic acid, but not CRP, predicts features of the metabolic syndrome independently of BMI in women. Int J Obes Relat Metab Disord 2004; 28:1004–1010.  Back to cited text no. 18
    
19.
Ghosh J, Datta S, Pal M. Role of sialic acid in prediction of diabetic retinopathy. Bangalore: Al Ameen Charitable Fund Trust; 2016.  Back to cited text no. 19
    
20.
Sillanaukee P, Ponnio M, Jaaskelainen IP. Occurrence of sialic acids in healthy humans and different disorders. Eur J Clin Invest 1999; 29:413–425.  Back to cited text no. 20
    
21.
Crook MA, Tutt P, Simpson H, Pickup JC. Serum sialic acid and acute phase proteins in type 1 and type 2 diabetes mellitus. Clin Chim Acta 1993; 219:131–138.  Back to cited text no. 21
    
22.
Sonnez H, Ozturk ZG, Ulutin T, Domanc N, Kokojlu E. Carbohydrate deficient transferring and sialidase level in coronary heart disease. Throm Res 2000; 99:311–315.  Back to cited text no. 22
    
23.
Krishnamurthy U, Halyal SS, Jayaprakash Murthy DS. 2015 Serum sialic acid and microalbuminuria in non insulin dependent diabetes mellitus. Biomed Res 2011; 22:31–34.  Back to cited text no. 23
    
24.
Yokoyama H, Jensen JS, Myrup B, Mathiesen ER, Ronn B, Deckert T. Raised serum sialic acid concentration precedes onset of microalbuminuria in IDDM. Diabetes Care 1996; 19:435–440.  Back to cited text no. 24
    
25.
Tomino Y, Inoue W, Watanabe S, Yagame M, Eguchy K, No-matymd Sakai H. Detection of glomerular sialic acids in patients with diabetic retinopathy. Am J Nephrol 1988; 8:21–26.  Back to cited text no. 25
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

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