ls0 ws1">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
Copyright © 2012 SciRes. OPEN ACCESS
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.
[1] Miyakis, S., Lockshin, M.D., Atsumi, T., Branch, D.W.,
Brey, R.L., Cervera, R., et al. (2006) International con-
sensus statement on an update of the classification criteria
for definite antiphospholipid syndrome (APS). Journal of
Thrombosis and Haemostasis, 4, 295-306.
[2] Grundy, S.M., Cleeman, J.I., Daniels, S.R., Donato, K.A.,
Eckel, R.H., Franklin, B.A., et al. (2005) Diagnosis and
management of the metabolic syndrome. An American
Heart Association/National Heart, Lung, and Blood In-
stitute Scientific Statement. Executive summary. Cardi-
ology in Review, 13, 322-327.
[3] Gharavi, A.E., Harris, E.N., Asherson, R.A. and Hughes,
G.R. (1987) Anticardiolipin antibodies: Isotype distribu-
tion and phospholipid specificity. Annals of the Rheu-
matic Diseases, 46, 1-6. doi:10.1136/ard.46.1.1
[4] Chobanian, A.V., Bakris, G.L., Black, H.R., Cushman,
W.C., Green, L.A., Izzo, J.L. Jr., et al. (2003) The sev-
enth report of the Joint National Committee on Preven-
tion, Detection, Evaluation, and Treatment of High Blood
Pressure: The JNC 7 report. Journal of the American
Medical Association, 289, 2560-2572.
[5] Filozof, C., Fernandez Pinill a, M.C. and Fernández-Cruz,
A. (2004) Smoking cessation and weight gain. Obesity
Research, 5, 95-103.
[6] King, H., Aubert, R.E. and Herman, W.H. (1998) Global
burden of diabetes, 1995-2025: Prevalence, numerical es-
timates, and projections. Diabetes Care, 21, 1414-1431.
[7] Kannel, W.B. and McGee, D.L. (1979) Diabetes and
cardiovascular disease. The Framingham study. Journal
of the American Medical Association, 241, 2035-2038.
[8] Ciarla, M.V., Bocciarelli, A., Di Gregorio, S., Tordi, A.,
Cotroneo, P., Marra, G., et al. (2001) Autoantibodies and
endothelial dysfunction in well-controlled, uncomplicated
insulin-dependent diabetes mellitus patients. Atheroscle-
rosis, 158, 241-246.
[9] Staub, H.L., Norman, G.L., Crowther, T., Da Cunha,
V.R., Polanczyk, A., Bohn, J.M., et al. (2003) Antibodies
to the atherosclerotic plaque components beta2-glyco-
protein I and heat-shock proteins as risk factors for acute
cerebral ischemia. Arquivos De Neuro-Psiquitria, 61, 757-
763. doi:10.1590/S0004-282X2003000500010
[10] Ranzolin, A., Bohn, J.M., Norman, G.L., Manenti, E.,
Bodanese, L.C., Von Muhlen, C.A., et al. (2004) Anti-
beta2-glycoprotein I antibodies as risk factors for acute
myocardial infarction. Arquivos Brasileiros de Cardiolo-
gia, 83, 141-144.
[11] Recuero, M.L., Silva, J.B., Norman, G.L., Von Muhlen,
C.A. and Staub, H.L. (2007) IgA antibodies to beta2-
glycoprotein I and carotid disease. Israel Medical Asso-
ciation Journal, 9, 495-496.
[12] Franck, M., Staub, H.L., Petracco, J.B., Norman, G.L.,
Lassen, A.J., Schiavo, N., et al. (2007) Autoantibodies to
the atheroma component beta2-glycoprotein I and risk of
symptomatic peripheral artery disease. Angiology, 58,
295-302. doi:10.1177/0003319707302493
[13] Krás Borges, R., Bodanese, L., Von Mühlen, C., Repetto,
G., Viehe, M., Norman, G., et al. (2011) Anti-beta2-
glycoprotein I autoantibodies and metabolic syndrome.
Arquivos Brasileiros de Cardiologia, 96, 272-276.
[14] Hendra, T.J., Baguley, E., Harris, E.N., Khamashta, M. H.,
Trembath, R.C., Hughes, G.R., et al. (1989) Anticardi-
olipin antibody levels in diabetic subjects with and with-
out coronary artery disease. Postgraduate Medical Jour-
nal, 65, 140-143. doi:10.1136/pgmj.65.761.140
[15] Gargiulo, P., Goldberg, J., Romani, B., Schiaffini, R.,
Ciampalini, P., Faulk, W.P., et al. (1999) Qualitative and
quantitative studies of autoantibodies to phospholipids in
diabetes mellitus. Clinical & Experimental Immunology,
118, 30-34. doi:10.1046/j.1365-2249.1999.01014.x
[16] Galtier-Dereure, F., Biron, C., Vies, M., Bourgeois, V.,
Schved, J.F. and Bringer, J. (1998) Vascular complica-
tions of diabetes mellitus: What role for phospholipid-
binding antibodies? Lupus, 7, 469-474.
[17] Triolo, G., Giardina, E., Scarantino, G., Seddio, G. and
Bompiani, G. (1989) Detection of anti-phospholipid (car-
diolipin, phosphatidylserine) antibodies in the serum of
patients with non insulin-dependent (type 2) diabetes
mellitus and macroangiopathy. Coexistence of antipla-
telet reactivity. Diabetes Research, 10, 63-67.
[18] Fields, R.A., Toubbeh, H., Searles, R.P. and Bankhurst,
A.D. (1989) The prevalence of anticardiolipin antibodies
in a healthy elderly population and its association with
antinuclear antibodies. Journal of Rheumatology, 16,
[19] Chakravarty, K.K., Gray, R. E., Webley, M., Byron, M.A.
and Wozniak, J. (1991) Prevalence of anticardiolipin an-
tibodies in the elderly British population. Postgraduate
Medical Journal, 67, 358-361.
[20] Tarkun, I., Hacihanefioglu, A., Tarkun, P., Cetinarslan, B.
and Canturk, Z. (2005) Anticardiolipin and anti-beta2
glycoprotein I antibody concentrations in patients with
type 2 diabetes mellitus. Diabetes Research and Clinical
Practice, 68, 181-187. doi:10.1016/j.diabres.2004.09.005
Copyright © 2012 SciRes. OPEN ACCESS