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VOLUME 9 NUMBER 2 • JUNE 2012
63
SA JOURNAL OF DIABETES & VASCULAR DISEASE
RESEARCH ARTICLE
Table 2.
Correlation between anti-OXLDL antibodies and cardiovascular
disease biomarkers.
Spearman
R
p
-value
Age (years)
–0.14
0.07
BMI (kg/m
2
)
–0.12
0.12
Waist circumference (cm)
–0.12
0.10
Hip circumference (cm)
–0.10
0.20
WHR
–0.03
0.70
SBP (mmHg)
–0.002
0.95
DBP (mmHg)
0.03
0.66
FBG (mmol/l)
–0.22
0.003
Post BG (mmol/l)
–0.22
0.006
HbA
1c
(%)
–0.22
0.003
TC (mmol/l)
–0.13
0.08
TG (mmol/l)
–0.15
0.04
HDL-C (mmol/l)
–0.01
0.90
LDL-C (mmol/l)
–0.11
0.15
Urine microalbumin (mg/l)
–0.02
0.71
Serum cotinine (ng/ml)
–0.15
0.047
Hs-CRP (mg/l)
–0.16
0.03
Full CVD (%)
–0.010
0.908
Hard CVD (%)
–0.03
0.768
BMI, body mass index; WHR, waist-hip ratio; SBP, systolic blood pressure;
DBP, diastolic blood pressure; FBG, fasting blood glucose; Post BG, two-hour
post blood glucose; TC, total cholesterol; TG, triglycerides; HDL-C, high-
density lipoprotein cholesterol; LDL-C, low-density lipoprotein choles-
terol; Full CVD, hard CVD or coronary insufficiency, angina pectoris, tran-
sient ischaemic attack, intermittent claudication or congestive heart failure;
Hard CVD, coronary death, myocardial infarction, fatal or non-fatal stroke.
Results are expressed as median (95% confidence interval).
Fig. 1.
Box plot representing anti-oxLDL antibody levels in normal subjects, and
those with normoglycaemia (
n
= 79), impaired fasting glucose (IFG) (
n
= 14),
impaired glucose tolerance (IGT) (
n
= 29), undiagnosed diabetes (DM) (
n
= 29),
known DM (
n
= 25), and self-reported diabetes. Undiagnosed diabetes was sig-
nificantly lower (
p
= 0.01) compared to normal subjects using Kruskal-Wallis
ANOVA.
Results
The study group consisted of 176 subjects of whom 114 (64.7%)
were females and 63 (35.3%) were males. The subjects were
categorised into those with hyperglycaemia [29 undiagnosed DM,
25 known DM, 14 impaired fasting glucose (IFG) and 29 impaired
glucose tolerance (IGT)] and 79 normoglycaemia (normal), and their
characteristics are presented as medians (95% confidence interval)
in Table 1.
By selection, glycated haemoglobin (HbA
1c
), fasting plasma
glucose and two-hour post 75-g glucose load blood glucose were
significantly higher in the hyperglycaemic group. Obesity indices,
BMI, waist–hip ratio, waist and hip circumferences and increased
CVD risk scores were significantly more prevalent in hyperglycaemic
individuals. However, tobacco exposure as assessed by serum
cotinine was more common in the normoglycaemic subjects. Anti-
oxLDL antibodies and HDL cholesterol levels were significantly lower
in the hyperglycaemic individuals.
Anti-oxLDL antibodies were further investigated according to the
individual glycaemic states (normal, IGT, IFG, undiagnosed diabetes
and self-reported diabetes) using ANOVA, and were found to be
lowest in individuals with undiagnosed diabetes (Fig. 1). Anti-oxLDL
antibodies presented significant negative correlations with hs-CRP,
fasting blood glucose, post two-hour glucose, HbA
1c
, triglycerides
and serum cotinine (Table 2). Furthermore, when correlations were
done on each study group, total cholesterol correlated negatively
with anti-oxLDL antibodies in normoglycaemic subjects (
r
=
–0.2883;
p
= 0.0100).
Multiple stepwise linear regression including anti-oxLDL
antibodies as the dependent variable showed that post two-
hour glucose, triglycerides and serum cotinine levels remained
independently associated with anti-oxLDL antibodies. Other
contributors to anti-oxLDL antibodies were total cholesterol, age
and waist–hip ratio; the last showed a positive association with
anti-oxLDL antibodies (Table 3).
Discussion
The inflammatory nature of atherosclerosis is well established.
Key to this is the oxidation of LDL, resulting in the formation of
immune complexes and the production of antibodies against
oxLDL.
3
It is well recognised that diabetes mellitus increases the
risk of developing cardiovascular diseases, and oxidation of LDL
is suggested to play a significant role in the pathogenesis of the
macrovascular complications observed in diabetic patients.
2
Antibodies against oxidised LDL have been detected in
healthy and diseased individuals,
9-11
however their role in disease
Table 3.
Variables that contribute to anti-oxLDL antibodies after multiple
linear stepwise regression.
Variable
β
Adjusted
β
p
-value
Post BG (mmol/l)
–0.255
–0.023
0.003
Serum creatinine (ng/ml)
–0.246
–0.0005
0.003
TC (mmol/l)
–0.109
–0.034
0.245
TG (mmol/l)
–0.144
–0.078
0.114
WHR
0.151
0.598
0.09
Age (years)
–0.096
–0.004
0.270
Post BG, two-hour post blood glucose; TC, total cholesterol; TG, triglycerides;
WHR, waist–hip ratio. Adjusted R
2
= 0.1198.