Open Journal of Internal Medicine, 2012, 2, 37-39 OJIM
http://dx.doi.org/10.4236/ojim.2012.21009 Published Online March 2012 (http://www.SciRP.org/journal/ojim/)
Anticardiolipin antibodies do not mediate macrovascular
complications of type 2 d i a betes
Caroline Eickhoff Copetti1, Myriam Perreynoud2, Melissa Claudia Bisi1, Henrique Luiz Staub1*
1Rheumatology Department, São Lucas Hospital, Faculty of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS),
Porto Alegre, Brazil
2Clinical Pathology Laboratory, São Lucas Hospital, PUCRS, Porto Alegre, Brazil
Received 7 September 2011; revised 11 November 2011; accepted 22 November 2011
ABSTRACT
The relationship of anticardiolipin antibodies (ACA),
markers of the antiphospholipid syndrome, with vas-
cular complications of diabetes mellitus is polemic.
This cross-sectional study assessed the frequency of
IgG, IgM, and IgA ACA in type 2 diabetics with and
without history of vascular events for the last 5 years,
and in healthy controls. ACA were detected by en-
zyme immunoassay. A total of 73 type 2 diabetics (33
with history of vascular events) and 54 healthy con-
trols were tested. Most diabetics were female (p =
0.003), and older than controls (p < 0.001). Mean du-
ration of disease was 10 years. The prevalence of a
positive ACA test was 7.4% in controls and 9.5% in
diabetics (p = 0.910). Comparison of healthy controls
and diabetics with and without history of macrovas-
culopathy, after adjusting for gender and age, showed
no significant differences as to the presence of ACA
(p > 0.09). ACA positivity rates were also similar
when diabetics with and without history of vasculo-
pathy were compared (p > 0.47). After adjusting for
gender, age, hypertension, and smoking status, a weak
but statistically insignificant association between IgM
ACA and diabetics with vasculopathy was found (ad-
justed OR 2.7; 9 5% CI 0.2 - 34.2; p = 0.441). Overall,
levels of IgG (r = 0.25 ; p = 0.005) and IgM ( r = 0.23; p
= 0.010) ACA were associated with increasing age. In
short, the frequency of a positive ACA test in type 2
diabetics (with or without previous macrovasculopa-
thy) was not significant as compared to healthy con-
trols. There was no association of ACA with vascular
events in patients with type 2 diabetes.
Keywords: Anticardiolipin Antibodies; Type 2 Diabetes
Mellitus; Myocardial Infarction; Cerebrovascular
Infarction
Anticardiolipin antibodies (ACA), as well as the lupus
anticoagulant and antibodies to beta2-glycoprotein (beta2-
gpI), are classical markers of the antiphospholipid syn-
drome (APS) [1]. The relationship of ACA with vascular
complications of diabetes is rather unclear.
This cross-sectional study assessed the frequency of
IgG, IgM, and IgA ACA in type 2 diabetics [2] with and
without history of macrovascular events (myocardial
and/or cerebral infarction) for the last 5 years, and in
healthy controls. ACA were detected by enzyme immu-
noassay (ORGENTEC Diagnostika GmbH—Anti-Car-
diolipin). Titers were considered as positive when above
10 GPL f or I g G ACA, 10 MPL for IgM ACA, and 7 u n it s
for IgA ACA [3]. The study was approved by the local
ethics committee.
Chi-square analysis were used for comparison of
categorical variables, and the Student’s t test was used
for comparison of continuous variables. A level of 5% (p
< 0.05) was considered significant. Odds ratios (OR) with
95% confidence intervals (95% CI) were calculated for
univariate analysis. Logistic regression with 95% CI was
performed to adjust the effects of gender, age, hyperten-
sion [4], and current smoking [5] in the OR. When
needed, Agresti correction was employed to obtain non-
adjusted OR. To co-relate quantitative variables, the
Pearson coefficient was utilized. All analyses used pro-
cedures of the SPSS for Windows, versi on 11.5, Chicago,
IL.
A total of 73 type 2 diabetics (33 with history of vas-
cular events) and 54 healthy controls were tested. Most
diabetics were female (p = 0.003), and older than con-
trols (p < 0.001). Mean dur ation of disease was 10 years.
The prevalence of a po sitive ACA test (any isotyp e) was
7.4% in controls (5.6% IgA ACA) and 9.5% in diabetics
(p = 0.910).
Comparison of healthy controls and diabetics with or
without history of macrov asculopathy, after ad justing for
gender and age, showed no significant differences in
ACA positivity (p > 0.09). ACA frequency rates were
*Corresponding a uthor.

C. E. Copetti et al. / Open Journal of Internal Medicine 2 (2012) 37-39 38
also similar when diabetics with and without recent his-
tory of vascular e ve nts were c ompared (p > 0.47).
Females significantly predominated in diabetics with-
out vasculopathy as compared to diabetics with previous
vascular events. After adjusting for gender, age, hyper-
tension, and smoking status, a weak but statistically in-
significant association of IgM ACA and diabetics with
vasculopathy was found. These data can be seen in Ta-
ble 1.
Overall, leve ls of IgG (r = 0.25; p = 0.005) and IgM (r
= 0.23; p = 0.010) ACA related to increasing age.
Type 2 diabetes comprise an independent risk factor
for atherosclerotic disease. The etiopathogenesis of the
micro and macrovascular complications of type 2 diabe-
tes are not fully understood. Macrovascular obstructions
affecting the coronary and cerebral arteries are the main
cause of mortality in diabetics [6,7]. ACA and endothe-
lial dysfuncion might be synergistic for vasculopathy in
insulin- dependent diabe t es [8].
For the last decade, we have documented a defined
association of IgA anti-beta2-gpI antibodies with cere-
bral ischemia [9], coronary disease [10], carotid disease
[11], and peripheral artery disease [12]. Only in one of
these studies [12], IgA ACA associated with the outcome.
More recently, we demonstrated an association of the
IgA anti-beta2-gpI antibody with metabolic syndrome;
once more, the ACA prevalence was low [13]. We there-
fore infer that ACA do not relate to acute or chronic
atherosclerotic disease, nor to metabolic syndrome. The
relationship of ACA with type 2 diabetes and diabetic
vasculopathy had not been so far evaluated in our re-
search center.
In the current study, ACA positivity was similar in
controls and type 2 diabetics (7.4% and 9.5%, respec-
tively). There was no statistical difference as to the ACA
prevalence in the two groups. The frequency of IgA ACA
in our healthy co ntrols (5.6%) was quite impressive, and
this is an issue to be further addressed. Differently from
our data, Hendra et al reported a significant frequency of
IgG ACA in diabetics with or without coronary disease
[14]. Gargiulo et al. described elevated levels of IgA
anti-phosphatidylethanolamine, but not ACA, in type 1
or 2 diabetics as compared to controls [15]. Similarly to
our findings, the prevalence of ACA in non-complicated
diabetes was irrelevant in another previous study [16].
When our two groups of diabetics were compared, a
weak association of IgM ACA with complicated diabetes
was suggested by the adjusted OR, but this finding was
statistically insignificant. Of interest, the frequency of
ACA in type 1 or 2 diabetics with macroangiopathy and
nephropathy was higher as compared to patients with
non-complicated or well-controlled disease [16]. Another
group of authors reported, in 1989, an increased positi-
vity for IgG and IgA ACA in type 2 diabetics with
macrovascular disease [17]. As seen, data concerning
prevalence of ACA in diabetes are incongruent.
We herein documented a significant correlation of IgG
and IgM ACA with increasing age. This is in accordance
with the study by Fields et al., whereby IgG and IgM
ACA were detected in 12% of the healthy elderly and in
2% of younger adults [18]. As opposed to that, ACA
positivity in the elderly was reported to be insignificant
and similar to younger populations [19].
In general terms, our results pointed to a insignificant
positivity for ACA in type 2 diabetes. A low prevalence
of ACA was seen in both complicated or non-compli-
cated diabetic populations. These data, although limited
by the small sample, do not favour a pathogenetic role
for ACA in type 2 diabetes and diabetic macrovasculo-
pathy. Our findings are corroborated by those reported by
Tarkun et al., which desvinculated ACA from vascular
complications of type 2 diabetes [20].
In summary, the frequency of a positive ACA test in
type 2 diabetes (complicated or not by macrovasculo-
Table 1. Clinical variables and frequency of anticardiolipin antibodies (ACA) in both group of diabetics.
Diabetics with
vascular event n = 33 Diabetics without vascular event n = 40 p Non-adjusted OR (95% CI) Adjusted OR*** (95% CI) p
Age (years)† 68.2 (±10.65) 65.9 (±9.1) 0.331‡ 1.0 (0.9 - 1.1) NC NC
Females 16 (48.5%) 33 (82.5%) 0.005* 0.2 (0.1 - 0.6) NC NC
Hypertension 29 (87.9%) 33 (82.5%) 0.744* 1.5 (0.4 - 5.8) NC NC
History of smoking 8 (24.2%) 11 (27.5%) 0.962* 0.8 (0.3 - 2 .4) NC NC
IgG ACA positive 0 1 (2.5%) 0.999* 0.6 (0.05 - 6.8)** NC NC
IgM ACA positive 3 (9.1%) 1 (2.5%) 0.475* 3.9 (0.4 - 39.4) 2.7 (0.2 - 34.2) 0.441
IgA ACA positive 0 2 (5.0%) 0.560* 0.4 (0.04 - 3.9)** NC NC
n: Sample number; †SD: Standard deviation; ‡Student t test; *Chi-square test; **Agresti correction; ***Adjustment for sex, age, hypertension and smoking; NC:
on-calculated. N

C. E. Copetti et al. / Open Journal of Internal Medicine 2 (2012) 37-39 39
pathy) did not significantly differ from controls. There
was no association of ACA with vascular events in
patients with type 2 diabetes. ACA do not appear to be
relevant in the pathogenesis of vascular complications of
type 2 diabetes.
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