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VOLUME 9 NUMBER 2 • JUNE 2012
61
SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
Correspondence to: Tandi Matsha
Timothy Tjaronda, Gloudina Hon, Adriaan Esterhuyse
Department of Biomedical Sciences, Faculty of Health and Wellness Science,
Cape Peninsula University of Technology, Bellville, Cape Town
Tel: + 27 (0)21 959 6366
Fax: +27 (0)21 959 6760
e-mail: matshat@cput.ac.za
Mogamat Hassan
Department of Nursing and Radiography, Faculty of Health and Wellness
Sciences, Cape Peninsula University of Technology, Cape Town
Rajiv Erasmus
Division of Chemical Pathology, Faculty of Health Sciences, University of
Stellenbosch, Cape Town
S Afr J Diabetes Vasc Dis
2012;
9
: 61–65.
Abstract
Background:
Hyperglycaemia is strongly associated with
increased oxidative stress, and the oxidation of low-density
lipoprotein (LDL) is suggested to play a significant role in the
pathogenesis of the macrovascular complications observed in
diabetic patients. We investigated the relationship between
auto-antibodies against oxidised low-density lipoprotein
(oxLDL), high-sensitivity C-reactive protein (hs-CRP) and
cardiovascular profile in individuals with hyperglycaemia.
Methods:
Antibodies against oxLDL and hs-CRP were
measured in 97 hyperglycaemic and 79 normoglycaemic
individuals. Gender-specific prediction for cardiovascular
disease (CVD) risk was calculated using the 30-year CVD
interactive risk calculator.
Results:
Anti-oxLDL antibodies were significantly lower in
hyperglycaemic individuals (p = 0.02). Significant correlations
were observed between levels of anti-oxLDL and hs-CRP (
r
= –0.16; 0.03), HbA
1c
(
r
= –0.22;
p
= 0.003), triglycerides (
r
=
–0.15;
p
= 0.04), serum cotinine (
r
= –0.15;
p
= 0.047), and
fasting blood glucose (
r
= –0.22;
p
= 0.003). The predictors
of anti-oxLDL antibodies after multiple stepwise linear
regression were levels of post two-hour blood glucose,
serum cotinine, total cholesterol, triglycerides, and age and
waist circumference; the last showing a positive association.
Conclusion:
Anti-oxLDL antibodies were reduced in subjects
with hyperglycaemia and these low levels were associated
with an increased cardiovascular disease risk score.
Keywords:
oxidisedLDL, antibodies, hyperglycaemia, cardiovascular
diseases, C-reactive protein
Submitted 6/4/2011, accepted 23/2/2012
Introduction
Diabetes mellitus (DM), particularly type 2 diabetes is highly
associated with atherosclerosis and therefore cardiovascular disease
(CVD). Mortality from CVD is two- to four-fold higher in those with
diabetes.
1
The link between diabetes and atherosclerosis is possibly
due to the association of hyperglycaemia with oxidative stress.
2
One of the key processes in the initiation of atherosclerosis is
the oxidation of low-density lipoprotein (LDL). Oxidised LDL (oxLDL)
promotes monocyte adhesion to injured or inflamed epithelium,
migration into the artery wall and differentiation into macrophages,
which take up oxLDL, leading tomacrophage foam cell formation and
subsequent atherosclerosis.
3
The binding of oxLDL to macrophages is
enhanced by C-reactive protein (CRP) via Fc
y
receptors.
4
Furthermore,
CRP has been shown to form complexes with oxLDL at physiological
calcium concentrations and such complexes have been detected in
DM patients with atherosclerosis.
5
The identification of CRP within early atherosclerotic lesions in
human coronary arteries provides a link that CRP is probably directly
involved in the intra-plaque inflammatory process.
6
Therefore CRP has
been proposed as a good biomarker for atherosclerotic inflammation
and among apparently healthy men and women, plasma levels of
CRP above 3 µg/ml are associated with future major cardiovascular
events.
7,8
Oxidised LDL is immunogenic, consequently antibodies against
OxLDL are generated and these antibodies have been shown to be
present in children,
9
healthy adults, and patients with CVD
10
and
DM.
11
However, there is controversy regarding the role of these
circulating antibodies in humans. In animal models, IgM anti-oxLDL
natural antibodies were shown to block the binding and degradation
of oxLDL by macrophages
in vitro
, suggesting a protective role of
these antibodies.
12,13
By contrast, IgG anti-oxLDL/beta2GPI antibodies
were shown to enhance macrophage uptake of oxLDL
in vitro
,
promoting the atherogenic process.
14
In humans, high titres of IgG anti-oxLDL antibodies have been
reported in children compared to adults, and these have been
suggested to modulate the antigen and thus protect against
atherosclerosis.
9
Conversely, elevated anti-oxLDL antibodies have
been shown in atherosclerotic lesions, linking them to a pathogenic
role in CVD.
15
Similarly in diabetes, controversial results have been
reported.
11,16,17
The aim of the present study was to investigate the relationship
between auto-antibodies against oxLDL, hs-CRP levels and
cardiovascular profile in individuals with hyperglycaemia, and
ascertain whether the levels of auto-antibodies against oxLDL were
reduced in hyperglycaemic individuals with a high prevalence of
diabetes.
Methods
The study was approved by the Cape Peninsula University of
Technology, Faculty of Health and Wellness Sciences ethics
Antibodies against oxidised LDL, and cardiovascular risk
factors in individuals with hyperglycaemia
TANDI MATSHA, TIMOTHY TJARONDA, GLOUDINA HON, ADRIAAN ESTERHUYSE, MOGAMAT
HASSAN, RAJIV ERASMUS