Vol.2, No.7, 708-712 (2010)
doi:10.4236/health.2010.27108
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Health
Platelet aggregation responses in type 2 diabetic
patients
Fatma Mutlu Kukul Güven1*, Abdülkerim Y ilmaz1, Hüseyin Aydin2, Ilhan Korkmaz1,
Sevki Hakan Eren1
1Emergency Medicine Deparment, School of Medicine, Cumhuriyet University, Sivas, Turkey;
*Corresponding Author:
2Biochemistry Lab, School of Medicine, Cumhuriyet University, Sivas, Turkey;
Received 12 February 2010; revised 12 March 2010; accepted 14 March 2010.
ABSTRACT
Diabetes mellitus (DM) is associated with platelet
dysfunction. In diabetic patients, alterations in
platelet functions, especially increased platelet
agregation, have been suggested to cause in-
creasing in cardiovascular morbidity and mo-
rtality or in accelaretion of athersclerotic proc-
ess. In this study, we aimed to investigate the
platelet aggregation response alterations and
the effects of DM duration, HbA1c, treatment op-
tions among the patients with Type 2 DM. Forty-
five patients (case group; 21 male, 24 female)
with Type 2 DM and forty-eight healthy indivi-
duals (control group; 22 male, 26 female) were
included in this study. Platelet aggregation was
determinated with Chorono-log 500 (USA) named
device by using Chorono-log/ADP, Chorono-log/
collagen and Chorono-log/epinephrine kits.
ADP-induced platelet aggregation was signifi-
cantly higher in the case group compared with
control group (p < 0.05). Epinephrine induced
platelet aggregation were significant in negati-
vely correlation with the diabetes duration (P <
0.05). Platelet aggregation responses did not
differ according to their treatment type (sulph-
onylurea or insulin) was statistically insignific-
iant among the case groups (p > 0.05). In con-
clusion, our findings supported that type 2 dia-
betes may interfere with platelet functions with-
out any relationship age, gender, the treatment
types and the regulation levels. These findings
supports that existence potential new factors or
mechanism affecting platelet agregation. The
subject requires more detailed studies in the
future.
Keywords: Platelet Aggregation; Diabetes;
Insulin; HbA1c
1. INTRODUCTION
Evidencies for abnormal platelet functions in diabetes
mellitus (DM) have been shown as: altered platelet func-
tions [1,2], increased aggregation of platelet that leads to
acceleration of atherogenesis [1], abnormal platelet acti-
vation suggested to cause micro or macro angiopaties
[2-4] and platelet hyperactivities [5,6].
The aim of this study was to investigate the platelet
aggregation response alterations and the effects of DM
duration, HbA1c, treatment options among the patients
with Type 2 DM.
2. METHOD
This study was performed in Cumhuriyet University
Medicine Faculty Emergency Department between Jan-
uary-December 2003.
Study population: Forty-five patients (case group; 21
male, 24 female) with Type 2 DM diagnosis and forty-
eight healthy individuals (control group; 22 male, 26
female) were included in this study. Case and controls
had not any other systemic disease except type 2 DM.
Neither of the patient of case group was diagnosed as
type 1 DM. nor of the participitants had a treatment
history by a drug that interferes platelet aggregation.
Blood sampling: A fasting state venous blood sample
were taken in vaccuated tubes for all participitans and
send to biochemistry laboratory within 30 minutes to
measure blood glucose and HbA1c. For platelet aggre-
gation responses measurement venous blood samples
were send to hematology laboratory within 30 minutes in
0.2 ml citrates containing tubes.
Study procedure: Blood glucose and HbA1c were
studied by standart laboratory methods. Platelet aggre-

F. M. K. Güven et al. / HEALTH 2 (2010) 708-712
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
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709
gation was determinated with Chorono-log 500 (USA)
named device by using Chorono-log/ADP, Chorono-log/
collegen and Chorono-log/epinephrine kits.
Statistical analysis: Data analysis were performed on
SPSS (Ver 13.0) software by using chi-square, studen-t,
Mann-Whitney U tests and correlation analysis.
3. RESULTS
The mean age was 58.68 ± 1.37 years in the case group
and 53.72 ± 2.10 years in the control group. When case
and control groups were statistically compared upon to
their mean age and gender the difference was insig-
nificant (P > 0.05) (Table 1). The mean glucose levels in
the case and control groups were as 224.44 ± 15.95 mg/dl
and 99.16 ± 11.84 mg/dl. The mean HbA1c level in the
case group was 9.59 ± 0.38 mg/dl. The mean duration of
diabetes in the case group was 8.06 ± 0.83 years. Sulfo-
nylurea drugs were used in 44.45% [20] patient and
insulin was preferred in 55.5% [25] patient for treatment.
Platelet aggregation responses induced with epinep-
hrine, collagen and adenosine diphosphate (ADP) were
measured and mean results were recorded as percen-
tage(%) for both groups. The difference between the
case and control groups were statistically insignificiant
in terms of platelet aggregation responses induced with
epinephrine and collagen (p > 0.05). Whereas; ADP-ind-
uced platelet aggregation was significantly higher in the
case group compared with control group. (Table 2).
Platelet aggregation responses induced with all three
activators were not in correlation with the ages in the
both groups. (Table 3).
Platelet aggregation responses induced with all three
activators were in negatively correlation with the diabetes
duration. However, the correlation were significant for
only epinephrine (P < 0.05). (Table 4).
When the platelet aggregation responses induced with
three activators in the case groups were compared with
HbA1c levels and the difference were not significant in
statistical analysis (p > 0.05). (Table 5).
Platelet aggregation responses did not differ according
to their treatment type (sulphonylurea or insulin) and
statistically it was insignificiant among the case groups
(p > 0.05). (Table 6).
4. DISCUSSION
Platelets functions are significant to understanding the
pathophysiology of vascular disease in diabetes. The role
of hyperglycemia is not clear in platelet hyperactivity in
diabetic patients [7].
Platelet dysfunction may develop before vessel wall
damage in diabetes [8,9]. Platelet dysfunction in diabetes,
including altered adhesion and aggregation, is hypersen-
sitivity to agonists [10].
Patient with type 2 DM had altered platelet functions
and increased platelet aggregation responses with agon-
ists [11,12].
Table 1. Epidemiological and laboratory properties of case and
control groups.
Cases
x
± Se
Controls
x
± Se P
n (f/m) 45 (24/21) 48 (26/22) p > 0.05
Mean Age (year) 58.68 ± 1.37 53.72 ± 2.10 p > 0.05
Mean time of DM
(year) 8.06 ± 0.83 - -
Treatment (OAD/ins)20/25 - -
HbA1c(mg/dL) 9.59 ± 0.38 - -
Blood glucose
(mg/dL) 224.44 ± 15.95 99.16 ± 11.84 P < 0.05
Table 2. Comparison of platelet aggregation responses in the
case and control groups.
Groups Epinephrine induced platelet
aggregation (%)
Collagen induced
platelet
aggregation (%)
ADP induced
platelet
aggregation (%)
Case 45.75 ± 2.26 54.82 ± 2.76 74.91 ± 3.61
Control 42.43 ± 2.78 51.39 ± 2.00 55.72 ± 1.77
p t = 0.91 p > 0.05t = 1.01 p > 0.05 t = 4.85 p < 0.05
Table 3. Correlation between the age and platelet aggregation
in the case and control groups.
Age Epinephrine
(%)
collagen
(%) ADP (%)
Case
58.68 ± 1.37
r = 0.11
p > 0.05
r = 0.03
p > 0.05
r = 0.13
p > 0.05
Control
53.72 ± 2.10 r = −0.11 p > 0.05
r = −0.09
p > 0.05
r = −0.07
p > 0.05
Table 4. Correlation between Diabetes duration and platelet
aggregation in the case group.
Epinephrine
(%) Collagen (%) ADP (%)
r = −0.31 r = −0.23 r = 0.11
Diabetes
duration
8.06 ± 0.83
p < 0.05 p > 0.05 p > 0.05

F. M. K. Güven et al. / HEALTH 2 (2010) 708-712
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Table 5. Correlation between HbA1c levels and the platelet aggregation in the case group.
HbA1c(mg/dl)
Case Group 5-7
n = 5
7-9
n = 17
9-11
n = 10
11- ↑
n = 13
P
Epinephrine (%) 48.40 ± 9.30 46.29 ± 3.04 41.60 ± 5.28 44.23 ± 4.48 KW = 4.21 p > 0.05
Collagen (%) 60.80 ± 3.74 52.88 ± 3.98 54.90 ± 7.23 55.00 ± 5.96 KW = 2.71 p > 0.05
ADP (%) 72.80 ± 4.1 72.94 ± 6.27 68.10 ± 9.74 83.53 ± 5.82 KW = 4.21 p > 0.05
Table 6. Correlation between treatment type and platelet aggregation in the case group.
case Oral Antidiabetic Drugs n = 20 Insulin n = 25 p
Epinephrine (%) 47.70 ± 3.23 44.20 ± 3.17 p = 0.367 p > 0.05
Collagen (%) 56.90 ± 4.35 53.16 ± 3.59 p = 0.775 p > 0.05
ADP (%) 76.75 ± 5.54 73.44 ± 4.84 p = 0.698 p > 0.05
In this study, three different activators caused to three
different aggregation responses and significantly incre-
ased aggregation response was predicted for only ADP.
This may depend on the presence of different possible
diabetic complications. Because, the presence of diabetic
complications may cause to variations in the platelet
agregations response. However, the diabetic complica-
tions were not examined in this study and we failed,
therefore, to conduct an exact conclusion on this subject.
Openly accessible at
The finding of increased aggregation response by
ADP in diabetic patients is in aggrement with the finding
reported previously [7,11,13,14]. Altough it was reported
previously that there was a possitive correlation between
the age and platelet aggregation responses [15,16]. We
failed to predicted such a correlation in this study. Kno-
bler et al. [1] found no relationship between the platelet
aggregation responces and the age of type 2 DM. Inter-
estingly, we found a significant negative correlation be-
tween the platelet aggregation responses induced with
epinephrine and diabetes duration. This finding suggest
that there are possible new factors or mechanisms other
than already known, having potence to interfere with
platelet aggregation responses.
Mean platelet volume (MPV) is a marker of platelet
function and activation. Larger platelets are more reac-
tive and aggregable. Therefore it can be said that is a
relationship between platelet function and diabetic com-
placations [17-20].
Increase in HbA1c concentration, indicative of wors-
ening glycemic control, was accompanied by increased
mean platelet volume which reflects deterioration of
platelet function [21]. Whereas Hekimsoy et al. [22] did
not found any correlation between HbA1c and MPV.
We found no relationship between HbA1c levels and
the platelet aggregation responses; in aggrement with the
findings of Mandal et al. [23] and of Hughes et al. [24].
Konya et al. [25] was found ADP-induced platelet ag-
gregate were significantly reduced in the group with
improved HbA1c.
The previous studies, except one [26], showed evi-
dencies that oral antidiabetic drugs (OAD) have im-
proving effects on platelet functions [27-30]. Another
study was found that in the patients with improved gly-
cemic control, gliclazide could inhibit ADP-induced pl-
atelet aggregation via the serotonin pathway [25]. Some
studies suggests that insulin may inhibit platelet function
at physiological concentrations [31,32], but enhance pl-
atelet aggregation at supraphysiological concentrations
[33,34]. However; Hu et al. [35] had found that even
physiological concentrations of insulin enhance platelet
activation both in healthy subjects and in type I diabetic
patient.
In our study, we found no significant difference in pl-
atelet aggregation responses regarding to the treatment
type; insulin or OAD.
In conclusion, our findings supported that there sev-
eral abmormalities in the platelet aggregation responses
in type 2 DM patients and that the differences are not in
correlation with control levels of blood glucose. The
subject requires more detailed studies in the future. This
findings suggest that there are possibly new factors or
mechanisms having potence to interfere with there plat-
elet aggregation responses.
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