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20 VOLUME 9 NUMBER 1 • MARCH 2012
RESEARCH ARTICLE SA JOURNAL OF DIABETES & VASCULAR DISEASE
complications (Table 3). Grossin et al . reported a low serum sRAGE
mean value in type 2 diabetics with nephropathy, compared to
those without vascular complications, explained by possible true
sRAGE consumption in an attempt to neutralise AGEs toxicity.32
Navarro et al. reported in diabetic patients a significant
relationship between serum TNF-α levels and bothmicroalbuminuria
and urinary proteins.33 Being a pro-inflammatory cytokine, TNF-α
is cytotoxic to glomerular, mesangial and epithelial cells, hence
inducing significant renal damage independent of alterations in
haemodynamic factors or effects of recruited inflammatory cells.34
A significantly higher plasma TBARS mean value was also noted
in nephropathy cases. Dave and Kalia demonstrated a higher level
of TBARS in diabetic nephropathy patients versus those without
nephropathy. 35
Retinopathy cases had significantly higher mean values of serum
sRAGE and plasma TBARS compared to those without vascular
complications (Table 3). Reports were inconsistent regarding the
level of serum sRAGE or plasma TBARS in diabetic retinopathy.36,37
Neuropathy cases on the other hand had significantly higher mean
serum values of sRAGE and TNF- α compared to those without
vascular complications (Table 3).
Haslbeck et al. suggested that activation of the AGE/RAGE/
NF-κB axis might contribute to the pathogenesis of diabetic
polyneuropathy.38 High TNF-α levels in neuropathy cases could be
attributed to the effect of hyperglycaemia, oxidative stress and
AGEs on the macrophages in a diabetic state, where activated
macrophages infiltrate nerve tissues, with the resultant local
production of much TNF-α, resulting in endothelial and nerve
fibre damage.39 Plasma TBARS mean value was significantly higher
in those with neuropathy compared to those without vascular
complications (Table 3). The results of previous studies were
inconsistent in that aspect. 40,41
Diabetic females suffering from ischaemic heart disease, one
of the macrovascular complications of diabetes, had significantly
higher levels of serum sRAGE and TNF-α compared to those
without vascular complications (Table 3). Nakamura et al. reported
a high serum level of sRAGE in diabetic patients with coronary
artery diseases.42 Tuttle et al. reported mildly increased serum TNF-α
levels in diabetic females with cardiovascular disease. 43 Plasma
TBARS mean value was significantly higher in our diabetic females
with ischaemic heart disease compared to those without vascular
complications, an observation also noted by Kesavulu et al .44
The number of diabetic females who suffered the cerebrovascular
complications of diabetes was too small to generate valid statistical
analysis. Regarding peripheral vascular disease, serum sRAGE and
plasma TBARS had significantly higher mean values in diabetic
females presenting with this type of macrovascular complication
compared to those without vascular complications. Lapolla et al.
demonstrated, in their study on type 2 diabetes patients, a higher
plasma malondialdehyde level and its strong association with
peripheral arterial disease.45
Conclusion
The low serum sRAGE mean value seen in diabetics without vascular
complications compared to those with vascular complications
implicated a true consumption of this decoy receptor molecule in
the neutralisation of AGEs, followed by elimination of complexes
via the reticulo-endothelial system, and hence a protective role
against the development of AGEs-induced vascular complications.
The high serum sRAGE mean level in diabetics with vascular
complications may represent a potential marker of diabetic vascular
complications. In addition, in all diabetic females, the significant
relation of sRAGE with duration of diabetes makes sRAGE an
attractive molecule to be used in follow-up studies to assess its
role as a predictor of development of vascular complications. Also,
the generalised chronic inflammation seen in diabetics induces the
production of pro-inflammatory cytokines such as TNF-α, with the
resultant triggering of oxidative stress markers. This is of major
importance in determining the degree of vascular damage.
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