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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 30, No 4, July/August 2019
196
AFRICA
menopausal women.
18,19
Whether the high level of pentosidine
observed in the cited studies was the cause or product of
osteoporosis is currently not clear. It is possible that our patient
control group, which was recruited from orthopaedic wards at
DGMAH, may have included non-diabetic postmenopausal
women with osteoporosis-related fractures. While this likelihood
was not verified in the current study, it might explain the
observed high levels of FAGE in the non-diabetic control group.
Previous studies reported in the literature have used circulating
levels of NO, ET-1 and PAI-1, among others, as surrogate
markers of endothelial dysfunction
in
vivo.
3,4,20
According to
these previous studies, serum levels of NO and its metabolites
are expected to be decreased, while serum levels of both ET-1
and PAI-1 are expected to be increased in conditions associated
with endothelial dysfunction, such as type 2 diabetes mellitus.
Therefore the findings of significantly reduced NO levels and
significantly higher serum levels of both ET-1 and PAI-1 are
in perfect agreement with the results of these previous studies.
However, these findings should be interpreted with caution, since
these circulating markers of endothelial dysfunction may come
from sources other than the vascular endothelium.
4,20
The observation in this study that serum NO levels were
negatively and significantly correlated with the age of the study
subject is in agreement with the well-documented observation
that endothelial function decreases with advanced age.
21,22
The
findings that serum levels of both TIAGEs and CML were
negatively and significantly correlated with serum NO levels
and positively and significantly correlated with serum levels of
ET-1 were also not unexpected, since high levels of some serum
AGEs are known to promote endothelial dysfunction through
their interaction with RAGE on the surface of the vascular
endothelial cell.
1
The finding that serum CML level was the only
parameter in this study that was significantly associated with
increased odds of developing endothelial dysfunction suggests
that serum CML is the major type of serum AGEs that interacts
with RAGE to promote endothelial dysfunction.
Limitations
There are several limitations that shouldbe taken into consideration
when interpreting results of this study. Firstly, the sample size
was small and study subjects were recruited from a single health
institution, therefore the findings could not be generalised beyond
the study samples. Secondly, the study was cross-sectional and
therefore cause and effect relationships could not be inferred from
the results. Thirdly, the possible confounding effect of exogenous
dietary and smoking-related AGEs on serum AGE levels was
not addressed. Fourthly, the control group selected for this study
might have confounded the results, particularly those of the
FAGEs. Fifthly, we did not concurrently measure serum AGE
levels and circulating markers of endothelial dysfunction of other
South African race groups for comparison purposes.
Despite these limitations, we believe that the results of this
study are of great interest in that they are the first to describe the
status of serum AGE levels among black South African patients
with type 2 diabetes, as well as the association between serum
AGE levels and endothelial dysfunction in black South African
patients with type 2 diabetes mellitus.
Conclusions
The results of this study showed that serum AGE levels
were significantly higher in type 2 diabetes patients than in
non-diabetic black South Africans, and with the exception of
CEL were not influenced by gender. In addition, serum FAGE
levels appeared to be positively associated with increasing age
of the subjects in the non-diabetic controls, but not in in the
diabetic subjects. Furthermore, the findings of this part of
the thesis showed that serum TIAGEs, CML, CEL, ET-1 and
PAI-1 levels were significantly elevated, whereas serum levels of
NO were significantly reduced in black South African patients
with type 2 diabetes compared to those in non-diabetic control
subjects. Moreover, the findings indicated that serum TIAGE
and CML levels, but not CEL and FAGE levels were correlated
with endothelial dysfunction in black South African patients
with type 2 diabetes mellitus. However, only serum CML levels
were associated with a higher odds of developing endothelial
dysfunction in these black South African type 2 diabetes patients.
We acknowledge the contribution of the nursing and medical personnel
as well as the phlebotomists at the diabetes clinic of Dr George Mukhari
Academic Hospital. We are grateful for the research funding obtained from
the National Research Foundation (grant no. TP1407187704).
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Table 3. Bivariate logistic analysis of the association between gender,
age and the major types of serum AGEs with endothelial dysfunction
(less than the first quartile of NO levels)
Parameters
COR
95% CI
p
-value
Age
0.600
1.372–2.62
0.460
Gender
1.040
0.996–1.12
0.296
TIAGEs (µg/ml)
0.348
0.014–8.916
0.523
CML (ng/ml)
1.910
0.655–0.893
0.013*
CEL (ng/ml)
1.172
0.963–1.638
0.112
FAGEs (Au)
0.991
0.882–1.038
0.141
COR: crude odds ratio; CI: confidence interval; TIAGEs: total immunogenic
advanced glycation end-products; CML: N
ε
-carboxymethyl-lysine; CEL:
N
ε
-carboxyethyl-lysine; FAGEs: fluorescent advanced glycation end-products;
*Significant at
p
<
0.05.