Within recent years, there has been considerable interest and research into sialic acid and its use as a potential inflammatory marker for diabetes mellitus . Previous reports have also indicated that serum sialic acid (SSA) concentrations were associated with an increased risk of cardiovascular disease in the diabetic population as well as the presence of micro-vascular diabetes related complications . Our study primarily focuses on the relationship between sialic acid and metabolic variables. We also wished to investigate the relationship between sialic acid and lipid profiles and to determine whether sialic acid concentrations were increased in patients with diabetes with and without microvascular complications. Previous studies have indicated that SSA concentrations are elevated in diabetics (both type 1 and type2) with and without complications, while others have reported no such correlation [13, 14]. Studies have also found that the presence or absence of this trend may be related to ethnicity .
Our research indicates that there is a significant increase (p < 0.01) in SSA concentrations in diabetic patients when compared to the control. This finding was also observed when patients with diabetic nephropathy and retinopathy were compared to the controls. It was noted that there was significant increase in SSA when diabetic group compared to diabetic retinopathy patients.
Serum sialic acid is a protein bound carbohydrate and occurs in combination with monosaccharides like galactose and mannose. Ninety percent is bound and almost none are free . In serum they are generally bound to acute phase proteins . There are several possible explanations for the increase in SSA concentrations. Several research studies have shown that the concentration of sialic acid in serum is elevated in pathological states when there is damage to tissue, tissue proliferation and inflammation . Research studies have also indicated that vascular permeability is regulated by sialic acid moieties. The vascular endothelium carries a high concentration of sialic acid and hence extensive microvascular damage associated with non-insulin dependant diabetes mellitus (NIDDM), could account for its shedding into the circulation. This leads to an increase in vascular permeability and overall increased SSA concentrations [6, 12].
Tissue injury caused by diabetic vascular complications stimulates local cytokine secretions from cells involved in the complications such as macrophages and endothelium. This induces an acute phase response which involves the release of acute phase glycoproteins with sialic acid from the liver into the general circulation again leading to increased SSA concentrations . Another plausible explanation for the increases SSA is that there may be a difference in the ratio between the two forms of erythrocyte sialidases which are important in maintaining the viability of the erythrocyte and its survival in the circulating blood .
As expected the difference between SSA concentrations between diabetes with complications and healthy subjects were statistically more significant (p < 0.000) than the difference between diabetics and healthy subjects (p < 0.010). In diabetic nephropathy and retinopathy there is a further increase in micro vascular damage which may have resulted in the greater increase in the SSA concentrations observed.
The increase in urine albumin seen in diabetics as compared to the controls can be interpreted as an early sign of nephrogenic changes in those individuals. The increase in urine albumin was seen with diabetic nephropathy was significantly higher than the other group subjects. This can be attributed to the degradation of the glomerular basement membranes as well as the increased hypertension which are key characteristics of diabetic nephropathy .
Microalbuminuria, the dominant feature of diabetic nephropathy is defined as an albumin excretion rate of 20–300 mg/24 hrs. The presence of microalbuminuria is a marker of endothelial dysfunction whether or not it progresses. This marker indicates an increased risk of generalized atherosclerosis and increased mortality from cardiovascular disease .
With regards to diabetes-related complications, a positive correlation was established between urine albumin levels and serum sialic acid using the Pearson's Correlation Test. This association was also seen in earlier studies . The actual cause of this occurrence is not known however several researchers have proposed a variety of mechanisms. One such mechanism includes the shedding of sialic acid into the circulation as a result of vascular endothelial damage. This result in the increased sialic acid as previously described. Vascular damage is seen throughout the body including the kidneys especially in diabetic nephropathy. As a result, there is increased filtration of albumin via the damaged glomeruli and hence an increased albumin loss in the urine .
With respect to the lipid profile the following observations were made. The cholesterol and LDL levels were unusually high in patients who were controls. This may be attributed to the unrestricted diets of these patients as well as possible inactive lifestyles . The unexpectedly lower LDL levels in the diabetics with and without nephropathy may be attributed to a low fat and carbohydrate diet . There was a significant increase in triglyceride levels when diabetics with and without microvascular complications compared with controls. An increased triglyceride level is a common feature of diabetes mellitus. Research has suggested that this is a result of reduced action of insulin on adipocytes resulting in suppression of lipolysis. This results in reduced hydrolysis of stored triglycerides and so a greater increase in non esterified fatty acids .
Increased triglyceride and LDL levels are risk factors for cardiovascular disease . There was an increased TG level but not the expected simultaneous increase in LDL levels amongst the four groups as explained above. Another finding of our study was that serum sialic acid was not related to cholesterol, triglyceride, LDL and HDL levels.
There was a positive association between SSA and systolic blood pressure and as stated before there was also a positive correlation between SSA and urine albumin excretion. Blood pressure and microalbuminuria are also risk factors for cardiovascular disease . Therefore it can be concluded that sialic acid may be considered as a possible marker for cardiovascular disease. Previous studies showed similar results [28, 29]. There was a positive correlation between waist to hip ratio and SSA however this relationship was not found with BMI. This indicates that central adiposity may be an important marker of NIDDM as opposed to general obesity since waist to hip ratio is a specific indicator of central adiposity . Central adiposity is a cardiovascular risk factor, hence these patients may have underlying microvascular complications and this may explain the correlation observed with SSA . This further supports the theory that SSA can be used as a marker for cardiovascular risk.
In addition to sialic acid another inflammatory marker was assessed, C- reactive protein (CRP). There was an insignificant increase in the CRP levels amongst the four groups. This could be explained by the inherent inflammatory state in diabetics with and without complications . There was no correlation between sialic acid and CRP suggesting that these inflammatory markers occur independently of each other.
In terms of limitations of this study the sample size could have been larger. Several patients were not certain about the type of medications that they were on and some of the patients were on antihypertensive drugs. The effects of these medications are unknown. Patients with diabetic nephropathy could also have had early signs of other complications such as retinopathy and neuropathy. There was no definite way of determining this and no way of assessing the impact of this on our study.
In the interest of future researchers who wish to conduct similar studies we have several recommendations that we wish to make: A larger sample size should be observed over a longer time period, multiple blood and urine samples from the same patient should be collected and 24 hr.urine samples should be collected instead of one time urine samples. Finally, we recommend that researchers take into account other diabetic complications such as diabetic retinopathy and diabetic neuropathy to allow for a more complete study.