Journal of Diabetes and Its Complications 29 (2015) 5963

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Journal of Diabetes and Its Complications

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Elevated beta2-glycoprotein I-low-density lipoprotein levels are

associated with the presence of diabetic microvascular complications
Ruijie Yu 1, Yunlong Yuan 1, Dongmei Niu, Jiaxi Song, Ting Liu, Jia Wu , Junjun Wang
Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China1 These authors have equal contributions to this work.

a r t i c l e

i n f o

Article history:
Received 15 June 2014
Received in revised form 30 August 2014
Accepted 18 September 2014
Available online 28 September 2014
Keywords:
2-Glycoprotein-I
Oxidized low-density lipoprotein
Type 2 diabetes mellitus
Diabetic complications
Microangiopathy

a b s t r a c t
Aims: To investigate serum beta2-glycoprotein I-low-density lipoprotein (2-GPI-LDL) and oxidized lowdensity lipoprotein (ox-LDL) levels in type 2 diabetes mellitus (T2DM) patients, and to further evaluate the
associations of 2-GPI-LDL with ox-LDL in vivo and with the presence of diabetic microvascular complications.
Methods: We determined 2-GPI-LDL, ox-LDL and small dense low density lipoprotein cholesterol (sdLDL-C)
levels in 236 T2DM patients with or without microvascular complications and 75 controls. The correlation
analyses, multiple linear regression analyses and logistic regression analyses were performed, respectively.
Results: Compared with controls, 2-GPI-LDL and ox-LDL levels were signicantly elevated in both groups of
T2DM patients and those with microvascular complications exhibited the more signicant increase than those
without complications. Serum 2-GPI-LDL levels were positively correlated with ox-LDL as well as sdLDL-C
levels in T2DM patients. Multiple linear regression analyses showed that ox-LDL was one of the independent
determinants of 2-GPI-LDL levels. Logistic regression analyses indicated that elevated 2-GPI-LDL and ox-LDL
levels had signicant predictive values for diabetic microvascular complications.
Conclusions: Elevated serum 2-GPI-LDL levels may be a serological hallmark of enhanced LDL oxidation
in vivo and closely associated with the presence of diabetic microvascular complications.
2015 Elsevier Inc. All rights reserved.

1. Introduction
Type 2 diabetes mellitus (T2DM) is known to be closely associated
with the dysregulation of glucolipid metabolism and aggravated
development of vascular complications (Pinhas-Hamiel & Zeitler,
2007). It has been demonstrated that hyperglycemia and hyperlipidemia in T2DM may enhance systematic oxidative stress, resulting in
the excessive production of lipid peroxides and subsequently
contributing to the pathogenesis of atherothrombosis and microangiopathy, which was the common pathogenetic mechanism underlying diabetic vascular complications (Dav, Falco, & Patrono, 2005;
Pinhas-Hamiel & Zeitler, 2007).
Small, dense low-density lipoprotein (sdLDL), the generally
acknowledged component of atherogenic lipoproteins, has been
characterized by the great susceptibility to oxidative modication
Disclosure of interest: The authors declare that they have no conicts of interest
concerning this article.
Correspondence to: J. Wu, Department of Clinical Laboratory, Jinling Hospital, 305
East Zhongshan Rd., Nanjing, 210002, China. Tel.: +86 25 80860181.
Correspondence to: J.J. Wang, Department of Clinical Laboratory, Jinling Hospital, 305
East Zhongshan Rd., Nanjing, 210002, China. Tel.: +86 25 80861177; fax: +86 25
84815775.
E-mail addresses: wujia0801@126.com (J. Wu), jjwang9202@gmail.com (J. Wang).
1
These authors have equal contributions to this work.
http://dx.doi.org/10.1016/j.jdiacomp.2014.09.010
1056-8727/ 2015 Elsevier Inc. All rights reserved.

(Hoogeveen et al., 2014). Oxidized low-density lipoprotein (ox-LDL),

as a recognized hallmark of in vivo lipids peroxidation, has been
considered to play a pivotal role in the initiation and progression of
atherosclerosis (Koenig et al., 2011). Beta2-glycoprotein I (2-GPI), the
main antigenic target for antiphospholipid antibodies, can bind ox-LDL
with higher afnity than native low-density lipoprotein (LDL) to form
stable and indissociable 2-GPI/ox-LDL complexes in vitro, consequently
being involved in antibody-mediated atherothrombosis in patients with
systemic autoimmune diseases (Kobayashi et al., 2003; Lopez, Simpson,
Hurley, & Matsuura, 2005). In vivo studies also revealed that increased
2-GPI/ox-LDL complexes existed in the bloodstream of patients with
non-autoimmune diseases accompanied by premature or accelerated
atherogenesis, indicating its potentially pathogenetic role in vascular
thromboembolic events (Greco et al., 2010; Kasahara et al., 2004; Lopez,
Hurley, Simpson, & Matsuura, 2005).
Enhanced oxidative stress in T2DM patients may lead to
endothelial cell damage and vascular dysfunction through various
mechanisms, particularly promoting microvascular thromboembolism and leading to the onset and development of diabetic
microangiopathy (Martn-Galln, Carrascosa, Gussiny, & Domnguez,
2003). Lopez, Hurley, et al. (2005) reported that the lower levels of
serum 2-GPI/ox-LDL complexes in T2DM patients taking cholesterollowering statins were in agreement with the antioxidant and antithrombotic properties of statins, suggesting that high 2-GPI/ox-LDL

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R. Yu et al. / Journal of Diabetes and Its Complications 29 (2015) 5963

levels might be a consequence of LDL atherogenic modication mediated

by oxidative stress. Nevertheless, no study has been published to show
direct association between serum 2-GPI/ox-LDL and ox-LDL levels in
T2DM. Furthermore, it still needed to study the differences in serum
levels of 2-GPI/ox-LDL between T2DM patients with and without
microvascular complications and the association of 2-GPI/ox-LDL
with the occurrence of microangiopathy. Therefore, this study was
undertaken to investigate serum 2-GPI-LDL, ox-LDL levels and their
associations in T2DM patients and to further evaluate the clinical
values of 2 -GPI-LDL for predicting the presence of diabetic
microvascular complications.

monoclonal anti-human ox-LDL antibody as the capture antibody and

the peroxidase conjugated monoclonal antibody against apolipoprotein
B as the detection antibody (Mercodia, Sweden). Serum sdLDL
cholesterol (sdLDL-C) levels were detected by use of the sdLDL-EX
Seiken kit (Denka Seiken, Japan) based on a homogeneous assay
adaptable to autoanalyzers (Ito, Fujimura, Ohta, & Hirano, 2011). The
levels of FPG (Wako Pure Chemical Industries, Japan) and serum
lipid/lipoprotein proles including total cholesterol (TC), triglyceride
(TG), high density lipoprotein cholesterol (HDL-C) and LDL cholesterol
(LDL-C) (Daiichi Pure Chemicals, Japan) were measured by enzymatic
procedures both on a model 7600 automatic analyzer (Hitachi, Japan).

2. Materials and methods

2.3. Statistical analysis

2.1. Study subjects

Data analyses were performed using SPSS version 16.0. Kolmogorov

Smirnov Test was used to evaluate the normality of variables and skewed
data were log-transformed to create a more normal distribution.
Normally distributed values were expressed as mean standard
deviation and the skewed distribution values were expressed as median
and interquartile range (P25P75). Comparisons of normal variables
among groups were analyzed by one-way ANOVA test and the
differences between groups were subsequently determined by Fisher
LSD test when appropriate. Comparisons of skewed variables which still
remained skewedly distributed after log-transformed among groups
were analyzed by KruskalWallis H test. The Chi-square test was used to
compare differences of gender among groups. Correlations between
variables were calculated by non-parametric Spearman rank coefcient
test. The stepwise multiple linear regression analyses (Pin = 0.05,
Pout = 0.10) were used to identify the inuencing factors for serum
2-GPI-LDL levels. The univariate and multivariate logistic regression
analyses were used to calculate the approximation of the relative risk,
odds ratio (OR) and 95% condence interval (CI) for selected variables. A
two-tailed P-value less than 0.05 was considered statistically signicant.

A total of 236 newly admitted T2DM subjects were randomly

enrolled from the department of endocrinology of Jinling Hospital
between September 2011 and April 2012. All the patients were
diagnosed according to the fasting plasma glucose (FPG) concentration and the presentation of clinical symptoms relevant to diabetes
based on the 1999 World Health Organization criteria (World Health
Organization, 1999). The exclusion criteria included the presence of
type 1 diabetes mellitus, gestational diabetes, diabetic macrovascular
complications (including hypertension, cardiovascular/cerebrovascular
accidents and lower extremity vascular diseases), chronic liver or renal
diseases, severe infections or other malignant diseases and previously
diagnosed diseases during drug withdrawal no more than 3 months. Of
these T2DM patients, 135 individuals diagnosed with microvascular
complications (including diabetes nephrology, diabetic retinopathy and
diabetic neuropathy) formed group 1, whereas group 2 consisted of 101
individuals diagnosed without any clinical signs and symptoms of
diabetic vascular complications.
75 healthy subjects who had contemporaneously visited Jinling
Hospital for routine health examination constituted the control group.
They were all found to be normal in physical, electrocardiography,
ultrasonography examination and serologically biochemical tests
without any other denitive diseases such as hyperlipemia, hypertension, cardiovascular or cerebrovascular diseases, diabetes mellitus,
severely impaired hepatic function and any recent surgery.
The blood was sampled at least 12 h after fasting and serum was
promptly separated by a 15 min centrifugation at 3000 rpm, and
stored at 80 C until analysis. This study protocol was approved by
the Ethics Committee of Jinling Hospital (2012GJJ-044) and all the
subjects provided written informed consent.

3. Results
3.1. Serum 2-GPI-LDL, ox-LDL and sdLDL-C levels in T2DM subjects
Compared with controls, serum 2-GPI-LDL and ox-LDL levels
were signicantly increased in both groups of T2DM patients and
sdLDL-C levels were elevated in patients with diabetic microvascular
complications. The levels of 2-GPI-LDL, ox-LDL and sdLDL-C were
higher in T2DM patients with complications than in those without
complications. The other lipid/lipoprotein status and the glucose
levels are shown in Table 1.

2.2. Laboratory methods

Serum 2-GPI-LDL levels were determined by a sandwich enzymelinked immunosorbent assay using the polyclonal anti-human 2-GPI
antibody as the capture antibody and the peroxidase conjugated
polyclonal antibody against apolipoprotein B as the detection
antibody (Zhang et al., 2011). Briey, 500 L of serum was rstly
incubated with MgCl2 (nal concentration 10 mol/L) at 37 C for 2 h
and then polyethyleneglycol-6000 (Sigma-Aldrich, United States) was
added to isolate 2-GPI-LDL from endogenous free form of 2-GPI. The
samples were incubated overnight at 4 C and then centrifuged at
10,000 rpm for 20 min. The precipitates were resuspended in 500 L
washing solution containing 0.5% gelatin and 0.05% Tween-20 in
0.01 mol/L PBS buffer solutions. A pooled fresh-frozen plasma sample
(mixed plasma from 50 healthy subjects) was used as the reference
serum of 2-GPI-LDL. Reference serum was also precipitated every
time as serum sample. The value of 2-GPI-LDL was expressed as 1
relative absorbance unit (U/mL).
The measurement of ox-LDL was analyzed by a commercially
available sandwich enzyme-linked immunosorbent assay using the

3.2. Associations among 2-GPI-LDL, ox-LDL, sdLDL-C and other lipid/

lipoprotein parameters in T2DM subjects
To study the relationship of 2-GPI-LDL, ox-LDL, sdLDL-C with
other lipid/lipoprotein parameters, Spearman rank correlation analyses were performed. Due to the similar associations among 2-GPILDL, ox-LDL, sdLDL-C and other lipid/lipoprotein parameters in T2DM
patients with or without microvascular complications (data not
shown), we combined two groups for the next analyses (n = 236).
In all the T2DM patients, the 2-GPI-LDL levels were positively
correlated with ox-LDL, sdLDL-C, TC and LDL-C; ox-LDL levels were
positively related with sdLDL-C, TC and LDL-C; sdLDL-C levels
exhibited positive correlations with TC, TG and LDL-C (Table 2).
To further explore the possible factors affecting 2-GPI-LDL and
ox-LDL levels in T2DM patients, the multiple linear regression
analyses were performed. Consequently, the ox-LDL, TC accounted
for 42.0% of the variation of 2-GPI-LDL levels, when all lipid/
lipoprotein parameters were included as independent variables
(Table 3). In addition, only 2-GPI-LDL (-coefcient = 0.382,

R. Yu et al. / Journal of Diabetes and Its Complications 29 (2015) 5963

Table 1
The clinical and biochemical characteristics in T2DM patients and controls.
Variables

Group 1 (n = 135)

Group 2 (n = 101)

Controls (n = 75)

Age, (years)
Male, n (%)
FPG (mmol/L)
TC (mmol/L)
TG (mmol/L)

57.14 15.81
83 (61.48%)
6.90 (5.609.00)
4.65 (3.805.30)
1.53 (1.142.43)
1.02 (0.881.25)

55.96 15.24
62 (61.39%)
7.70 (6.3010.60)
4.30 (3.705.00)
1.44 (0.971.92)
1.07 (0.891.26)

54.32 16.42
46 (61.33%)
4.60 (4.304.8)
4.38 (4.034.78)
0.87 (0.641.05)
1.61 (1.381.87)

2.68 0.82

2.55 0.62

0.79 (0.581.08)

0.70 (0.570.93)

HDL-C
(mmol/L)
LDL-C
(mmol/L)
sdLDL-C
(mmol/L)
ox-LDL (U/L)
2-GPI-LDL
(U/mL)

2.96 1.12

1.02 (0.621.38)

,#

46.62 (33.5460.36), # 41.08 (28.4254.23) 25.83 (20.4236.25)

1.10 (0.781.43) , ## 0.86 (0.651.20)
0.80 (0.591.06)

These variables were log-transformed before analyses. Group 1: T2DM patients

with microvascular complications; Group 2: T2DM patients without complications.

Compared with Controls: P b 0.05.

Compared with Controls: P b 0.01.

#
Compared with Group 2: P b 0.05;
##
Compared with Group 2: P b 0.01.

P b 0.001) was the signicantly independent predictor for ox-LDL

levels (adjusted R 2 = 0.141) and both TC (-coefcient = 0.690,
P b 0.001) and TG (-coefcient = 0.200, P b 0.001) were the
signicantly independent determinants of sdLDL-C levels (adjusted
R 2 = 0.605).

3.3. Associations of 2-GPI-LDL, ox-LDL and sdLDL-C with the presence of

diabetic microvascular complications
The univariate and multivariate logistic regression analyses were next
performed to evaluate the possible associations of 2-GPI-LDL, ox-LDL or
sdLDL-C with diabetic microvascular complications, respectively.
As shown in Table 4, the univariate analyses revealed that
increased 2-GPI-LDL and ox-LDL levels were signicantly related to
the presence of T2DM with or without microvascular complications,
and high sdLDL-C levels were only associated with the presence of
diabetic microvascular complications, respectively. In multivariate
analyses, adjusting for age, gender and other serum lipid/lipoprotein
levels, elevated 2-GPI-LDL and ox-LDL still had signicantly
predictive values for the presence of diabetic microvascular complications, and only high ox-LDL levels were associated with the
presence of T2DM without complications, respectively.

4. Discussion
The present study found that both 2-GPI-LDL and ox-LDL levels
were signicantly increased in T2DM patients with microvascular
complications. The 2-GPI-LDL levels were independent correlated with
ox-LDL in T2DM patients. Elevated 2-GPI-LDL and ox-LDL levels were
associated with the presence of microvascular complications in T2DM.

61

Table 3
Multiple linear regression analyses of possible factors affecting 2-GPI-LDL levels in
T2DM patients (n = 236).
Unstandardized
coefcients

Standardized coefcient

Beta

SE

Independent variables in the model

Constant
0.354
0.138
TC
0.277
0.031
0.558
ox-LDL
0.004
0.001
0.208
Independent variables excluded from the model
TG
0.092
HDL-C
0.035
LDL-C
0.140
sdLDL-C
0.121

P-value

0.011
b0.001
0.001
0.143
0.570
0.163
0.180

The dependent variable was 2-GPI-LDL (adjusted R2 = 0.420). All lipid/lipoprotein

variables on the correlation analyses were used for independent variables. P b 0.05 was
considered statistically signicant.

2-GPI, as a member of the plasma complement control protein

superfamily, has been characterized by its ability to bind lipoproteins
and other negatively charged materials (Kobayashi et al., 2003; Lopez,
Simpson, et al., 2005). It has been demonstrated that 2-GPI could
interact with ox-LDL via 7-ketocholesterol having a w-carboxyl acyl
chain to form covalently bound 2-GPI/ox-LDL complexes in vitro
(Kobayashi et al., 2003; Lopez, Simpson, et al., 2005). Circulating
2-GPI/ox-LDL complexes also existed in patients with signicant
atherothrombotic vascular involvement (Greco et al., 2010; Lopez,
Hurley, et al., 2005; Lopez, Simpson, et al., 2005). In the present study,
serum 2-GPI-LDL and ox-LDL levels were found to be signicantly
increased in both groups of T2DM patients. It has been known that
dysregulation of glucolipid metabolism in T2DM predisposed individuals to premature atherosclerosis and further contributed to the
accelerated thrombosis (Dav et al., 2005; Pinhas-Hamiel & Zeitler,
2007). The ox-LDL has been widely recognized as the major atherogenic
lipoproteins (Koenig et al., 2011). The 2-GPI/ox-LDL complexes may
promote the accelerated intracellular accumulation of ox-LDL in the
presence of 2-GPI mediated by anti-2-GPI antibodies and further
contribute to foam cell formation (Kajiwara, Yasuda, & Matsuura, 2007),
which revealed the pathogenetic relevance of 2-GPI/ox-LDL complexes
in atherogenesis. Consistently, the colocalization of 2-GPI and ox-LDL
has also been found in the arterial intima of atherosclerotic lesions
(George et al., 1999). Thus, elevated 2-GPI/ox-LDL complexes and
ox-LDL levels may be related with the pathogenesis of atherothrombotic
events in T2DM patients. Interestingly, we also observed the signicant
correlation between serum 2-GPI-LDL and ox-LDL levels in T2DM.
Furthermore, ox-LDL was one of the independent determinants of
2-GPI-LDL levels and only 2-GPI-LDL was the independent predictor
for ox-LDL levels. Since the sandwich ELISA for detecting 2-GPI-LDL in
this study could capture all of 2-GPI complexes with oxidization
modied LDL, other modied forms of LDL (such as MDA-modied LDL
and acetylated LDL) as well as native LDL (if existing), the independent
linkage of 2-GPI-LDL with ox-LDL but not with native LDL (represented
by LDL-C) may directly provide the striking evidence supporting that
ox-LDL was the preferential form interacted with 2-GPI and high

Table 2
Spearman's correlation coefcients among 2-GPI-LDL, ox-LDL, sdLDL-C and other lipid/lipoprotein parameters in T2DM patients (n = 236).
Variables

TC

TG

HDL-C

LDL-C

sdLDL-C

ox-LDL

2-GPI-LDL

2-GPI-LDL

r = 0.557
P b 0.001
r = 0.296
P b 0.001
r = 0.682
P b 0.001

r = 0.168
P = 0.015
r = 0.064
P = 0.369
r = 0.635
P b 0.001

r = 0.112
P = 0.105
r = 0.008
P = 0.908
r = 0.082
P = 0.243

r = 0.495
P b 0.001
r = 0.330
P b 0.001
r = 0.485
P b 0.001

r = 0.387
P b 0.001
r = 0.167
P = 0.024

r = 0.406
P b 0.001

r = 0.167
P = 0.024

r = 0.406
P b 0.001
r = 0.387
P b 0.001

ox-LDL
sdLDL-C

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R. Yu et al. / Journal of Diabetes and Its Complications 29 (2015) 5963

Table 4
Univariate and multivariate logistic regression analyses for the clinical predictive
values of 2-GPI-LDL, ox-LDL and sdLDL-C.
Group

Univariate analysis&

Group 1: T2DM
2-GPI-LDL
ox-LDL
sdLDL-C
Group 2: T2DM
2-GPI-LDL
ox-LDL
sdLDL-C

patients with microvascular complications (n = 135)

6.83 (2.64, 17.68)
b0.001
4.34 (1.05, 18.05)
1.07 (1.04, 1.09)
b0.001
1.04 (1.01, 1.07)
6.16 (2.50, 15.19)
b0.001
0.42(0.07, 2.64)
patients without complications (n = 101)
3.25 (1.25, 8.48)
0.016
2.62 (0.63, 10.93)
1.06 (1.03, 1.09)
b0.001
1.05 (1.02, 1.08)
2.11 (0.84, 5.32)
0.114
0.26(0.04, 1.70)

Unadjusted OR (95% CI)

Multivariate analysis$
P-value

OR (95% CI)

P-value
0.043
0.009
0.352
0.186
0.004
0.160

In univariate and multivariate logistic regression analyses, group 1, group 2 or the

control group was treated as a dependent three-category variable.
&
Only one variable of 2-GPI-LDL, ox-LDL and sdLDL-C was included in the model.
$
The age, gender and serum lipid/lipoprotein levels were adjusted in the model. OR
was considered signicant when the lower limit of the 95% CI was N1.0. P b 0.05 was
considered statistically signicant.
Reference category: the control group.

2-GPI-LDL levels may be mainly attributed to the increase of ox-LDL

levels. Elevated 2-GPI-LDL may serve as a serologically relevant
hallmark of enhanced LDL oxidation. Additionally, it was also sufciently
available for measuring the complexes of 2-GPI binding to LDL particles
with different oxidation degrees in different sites (from minimally
ox-LDL to extensively ox-LDL). Thus, our 2-GPI-LDL assay had a wider
detection range than the reported 2-GPI/ox-LDL method (Kobayashi
et al., 2003; Lopez, Hurley, et al., 2005; Lopez, Simpson, et al., 2005) and
would better reect the levels of pathogenic LDL in vivo. Similarly, we
also analyzed 2-GPI-Lp(a) levels using the same capture antibody
against human 2-GPI in patients with T2DM and coronary artery
disease (Wang et al., 2012; 2013).
In T2DM patients, glucolipid metabolism alterations caused by
insulin resistance may aggravate the imbalance of oxidant/antioxidant
systems, leading to increased reactive oxygen species and subsequent
lipids peroxidation, which further played a crucial role in the
progression of microvascular complications (Martn-Galln et al.,
2003). In addition, the fat deposition in microcirculation may also
contribute to the deterioration of microangiopathy (Dav et al., 2005;
Martn-Galln et al., 2003; Pinhas-Hamiel & Zeitler, 2007). In this study,
the 2-GPI-LDL and ox-LDL levels showed the more signicant increase
in patients with diabetic microvascular complications than in those
without any vascular complications, while sdLDL-C levels were only
elevated in patients with microvascular complications. The above
discrepant results may be explained by the fact that T2DM patients
with microvascular complications were in the relatively advanced stage
of diabetes and their dysregulation of lipid metabolism (represented by
elevated LDL-C) was more severe than those without any vascular
complications. Additionally, we found no signicant change in TC levels
(one of the independent determinants of sdLDL-C levels) between the
T2DM patients with and without complications, which may be also
responsible for the no signicant increase of sdLDL-C levels in patients
without complications. It has been demonstrated that enhanced
oxidative stress could occur in the early stage of developing diabetes
(Martn-Galln et al., 2003) and ox-LDL may function as the
particularly sensitive biomarker (Koenig et al., 2011; Yan, Mehta,
Zhang, & Hu, 2011). Consequently, ox-LDL levels still had a signicant
increase in patients without complications. The excessive generation of
circulating lipid peroxides may contribute to the aggravation of
endothelial dysfunction and cells oxidative injuries induced by
systematic oxidative stress, further promoting the onset
and development of microvascular thromboembolism in T2DM
patients (Martn-Galln et al., 2003). Strikingly, both 2-GPI-LDL
and ox-LDL levels showed signicant associations with the presence
of T2DM with microangiopathy and only ox-LDL levels exhibited

signicant association with the presence of T2DM without complications. Since high ox-LDL levels have been regarded as the direct
evidence for the enhanced oxidative stress in vivo, the imbalance
of oxidant/antioxidant systems in diabetes may initially lead to
the elevation in ox-LDL levels and subsequently result in the
increased 2-GPI-LDL levels. Thus, ox-LDL levels may consequently
exhibit the more obvious association with the presence of T2DM
without complications (the early stage of diabetes) than 2-GPI-LDL.
The ox-LDL has been reported to exert intensive cytotoxic effects to
human vascular endothelial cells and smooth muscle cells, subsequently
participating in the pathogenesis of diabetic microangiopathy (Koenig
et al., 2011; Yan et al., 2011). High 2-GPI-LDL levels, as a consequence of
oxidative lipids storage, may reect the oxidant/antioxidant imbalance
and consequently exhibited the close association with the presence of
diabetic microvascular complications.
In conclusion, the present study demonstrated that serum 2-GPILDL and ox-LDL levels were signicantly increased in T2DM patients,
especially in those with microvascular complications. The 2-GPI-LDL
levels were independently correlated with ox-LDL in T2DM patients.
Elevated 2-GPI-LDL levels may be a serologically relevant hallmark of
enhanced LDL oxidation. Furthermore, elevated 2-GPI-LDL levels
may be closely associated with the presence of diabetic microvascular
complications. These ndings may contribute to the understanding of
the pathogenetic role for circulating 2-GPI-LDL in T2DM. Further
studies are needed to validate these associations and to elucidate
pathophysiologic mechanisms of circulating 2-GPI-LDL in microangiopathy of T2DM.

Conict of interest
The authors declared no conict of interest.
Acknowledgments
This work was supported by grants from the National Natural
Science Foundation of China (NSFC 81271904), the Special-funded
Program on National Key Scientic Instruments and Equipment
Development of China (2012YQ 03026109) and the Jinling Hospital
Foundation (No. 2014051).
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