Fibrinolytic, Platelets and Endothelial Microparticles Abnormalities among Obese Type 2 Diabetic Patients--Juniper Publishers
JUNIPER
PUBLISHERS- OPEN ACCESS JOURNAL OF DIABETES & OBESITY
Abstract
Background: The prevalence of
cardiovascular disorders is progressively increased among type diabetic
(T2DM) patients. While, the influence of association between obesity and
T2DM on the level of platelets and endothelial microparticles remain to
be fully elucidated.
Objective: The aim of this was to
measure the abnormalities of Fibrinolytic parameters, fibrinogen,
platelets and endothelial microparticles among obese T2DM patients.
Materials and Methods: Fifty
non-smokers obese type 2 diabetic patients were included in this study.
The mean age was47.13±5.42 year and mean body mass index was 33.34±4.11
kg/m2 refers as the first group (A). Initially, a physician at King
Abdulaziz University Hospital examined all participants; their medical
history was taken to collect information about general condition,
physical activity and current medications if any. All subjects with any
cardiovascular conditions (those with a known history of uncontrolled
hypertension, congenital and rheumatic heart diseases), any pulmonary
disease (obstructive or restrictive lung diseases), were excluded from
the study. In the other hand another fifty non-diabetic subjects not
suffering of any disease, were participated in the study as a control
group refers as (B).
Results: FDetailed baseline
characteristics of the patients with T2DM and healthy controls showed a
significant difference for all characteristics of the diabetic patient’
svs controls, except in the age. However, the comparison between values
of BMI, tPA: Ag, fibrinogen, PAI-1: Ac, PMP CD41+ and EMP CD144+ for
group (A) and group (B), there were statistical significant differences.
However, the relationship between tPA: Ag, fibrinogen, PAI-1: Ac, PMP
CD41+, EMPCD144+ and BMI , both groups showed a strong direct
relationship.
Conclusion: There was a positive
association between obesity and the elevated biomarkers of endothelial,
platelets microparticles and Fibrinolytic parameters abnormalities among
type 2 diabetic patients.
Keywords: Obesity: Melanocortin type-4 receptor; MC4R; Pharmacological agent; Diet; Bariatric surgery; Weight lossKeywords: Sleeve gastrectomy; Roux en Y gastric bypass leak; Fistula; Restrictive surgery
Introduction
The prevalence of both diabetes associated with
obesity is on the rise [1]. The worldwide estimation of diabetics was
171 million in 2000, however this number will be projected to 366
million by 2030 [2] along with increase in mortality rate among patients
with diabetes [3]. However, the economic impact of diabetes is great
which 147 billion US dollars was in 2008 [4,5]. Cardiovascular
complications are more common among obese individuals with type 2
diabetes (T2DM) [6] which is the main cause of higher mortality rate
among obese T2DM [7]. Moreover, level of microparticles (MPs) can be
considered as essential biomarkers of cardiovascular risk [8].
Endothelial microparticles are indicators for
vascular tone, coagulation, endothelial inflammation and stress/damage
of the endothelial cell [9]. However, platelet micro particles that
released from activated platelets are indirect biomarker for endothelial
dysfunction as it indicates increased inflammation and abnormal
coagulation [10-17]. The aim of this was to measure the abnormalities of
Fibrinolytic parameters,fibrinogen, platelets and endothelial
microparticles among
obese T2DM patients.
Materials and Methods
Subjects
Fifty non-smokers obese type 2 diabetic patients visiting
King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were
included in this study. The mean age was 47.13±5.42 year and
mean body mass index was 33.34±4.11 kg/m2 refers as the first
group (A). Initially, a physician at King Abdulaziz University
Hospital examined all participants; their medical history was
taken to collect information about general condition, physical
activity and current medications if any. All subjects with any
cardiovascular conditions (those with a known history of
uncontrolled hypertension, congenital and rheumatic heart
diseases), any pulmonary disease (obstructive or restrictive
lung diseases), were excluded from the study. In the other hand
another fifty non-diabetic subjects not suffering of any disease,
were participated in the study as a control group refers as (B).
The Ethics Committee of the Faculty of Applied Medical Sciences,
King Abdulaziz University, approved this study. All participants
signed a written informed consent.
Evaluated parameters
Overnight fasting venous blood samples were taken from
ante cubital vein puncture were used for the study of lipid
profile analysis, while the other two tubes contained (EDTA) for
complete blood count, HbA1c and sodium citrate for coagulation
and microparticles studies using a fully automated analyzer
machine(Dimenition RxL, Diagnostics) at king Abdulaziz
University Hospital.
Centrifugation of the whole blood at 1500 xg for 10 min was
done to have the platelet poor plasma which was then separated
and stored at (-80°C) until analysis.
Analysis of coagulation and Fibrinolytic parameters
The PPP samples were processed with an enzyme linked
immune absorbent assay (ELISA) kits for the determination
of plasma tPA and PAI-1 activities and antigens and the
measurement for activities was performed using Chromolize™
tPA and Spectrolyse® pL PAI Biopool, Umea, Sweden). However,
fibrinogen level was measured using Zymutest Fibrinogen,
ELISA, Hyphen Biomed, France.
Microparticles preparation and quantification
Flow cytometric analysis was used for the measurement of
changes in platelets activities in type 2 diabetic patients.50 μ
PPP was incubated with different monoclonal antibodies (5 μl
CD41 FITC and 5μl CD144 PE) for 30 min at 4oC in a dark place.
The measurement of these markers was performed by using
four color FACSCalibur®cytometer.Prior to flow cytometric
analysis 30μl of flow Trucount Beads (BD Biosciences),was added to microparticles quantization allowing the calculation
of circulating endothelial and platelet derived microparticles
(EMP) number / μl PPP [18,19].
Evaluation of anthropometric parameters
Measurements of weight and height for both participant
groups were performed by using a digital stadiometer (JENIX DS
102, S. Korea), for the height and body weight were measured on
a balance scale (HC4211, S. Korea) then, Body Mass Index (BMI)
was computed as Body weight/Height2.
Statistical analysis
Independent “t” test was used to compare the investigated
parameters between both groups (P<0.05). However, the degree
of correlation body mass index and Fibrinolytic, endothelial
and platelets microparticles was calculated with Pearson’s
correlation coefficients (r).
Results
Detailed baseline characteristics of the patients with T2DM
and healthy controls were presented in Table 1. There was
a significant difference for all characteristics of the diabetic
patient’s vs controls, except in the age (Table 1). Concerning the
comparison between values of BMI, tPA: Ag, fibrinogen, PAI-1:
Ac, PMP CD41+ and EMP CD144+ for group (A) and group (B),
there were statistical significant differences as seen in (Table
2). The relationship between tPA: Ag, fibrinogen, PAI-1: Ac, PMP
CD41+, EMPCD144+ and BMI, both groups showed a strong
direct relationship (Table 3).
Discussion
The cardiovascular disorders are three times more frequent
among diabetics and mortality rate may reach about 50–75% of
diabetic population due to coronary artery disease [20,21]. MPs
are biomarkers that can be of value in prediction of risk factors
of cardiovascular disease, and as potential targets of therapy
[22]. Therefore, this study was a trial to measure the coagulation
parameters, platelet and endothelial MPs in T2DM patients
compared to control subjects.
The principal findings of in this study included an increased
BMI that were positively correlated with higher values of t-PA:
Ag, PAI-1: Ac, EMP-CD144+ and PMPCD41+levels in obese T2DM
patients. These findings agreed with many previous studies [23-
29]. The obtained results in this study, indicated that PMP-CD41+
were significantly increased among T2DM patients compared
to the healthy control group which agreed with Tan et al. [30]
who are the first to prove that the symptomatic atherosclerosis
is usually associated with increased PMPs in T2DM patients. In
addition, results in this study illustrated a significant increase
in the circulating levels of EMP-144+ among T2DM compared
to the healthy subjects. Moreover, Meigs et al. [31] found that
CD62E+ (E selecting) EMPs are elevated among T2DM patients.
However, Tramontano et al. [32] and Helal et al. [33] stated
that diabetic patients have relatively high level of CD31+ EMPs
than non-diabetic subjects. Moreover, MP levels have been
shown in multiple studies to be higher in diabetics than nondiabetics
[30-32]. While, Koga et al. [30] conducted a study on
232 diabetics and 102 non-diabetics in Japan, endothelial MP
levels were about twice as high among the diabetics. In addition,
Jung et al. reported an association between endothelial MPs with
macro vascular complications among diabetics [30].
Our study founded a positive association between BMI and
EMP& PMP, which may be caused by the deleterious impact of
visceral fat depot in over production of the MP as obesity induce
a state of low systemic inflammatory state and causing chronic
oxidative stress that, trigger release of MP [33,34].Finally, our
results proved that levels of PAI-1 and t-PA were significantly
increased among T2DM patients in comparison to healthy
subjects.
Conclusion
There was a positive association between obesity and the
elevated biomarkers of endothelial, platelets microparticles and
Fibrinolytic parameters abnormalities among type 2 diabetic
patients.
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