International Journal of Research in Medical Sciences

Dubey I et al. Int J Res Med Sci. 2017 Mar;5(3):1042-1047

www.msjonline.org pISSN 2320-6071 | eISSN 2320-6012

DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20170659
Original Research Article

A study to find correlation of platelet indices with HbA1c in diabetic

patients with absence/presence of vascular complications
Ishan Dubey*, Bindu Singh Gaur, Roma Singh

Department of Pathology, L.N Medical College, Bhopal, Madhya Pradesh, India

Received: 04 January 2017

Revised: 11 January 2017
Accepted: 04 February 2017

*Correspondence:
Dr. Ishan Dubey,
E-mail: drishandubey@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Diabetes Mellitus is a global pandemic disease. The increased platelet activity is emphasized to play a
role in the development of vascular complications of the metabolic disorder. Mean platelet volume (MPV) is an
indicator of average size and activity of platelets. This study was conducted to find correlation of platelet indices with
HbA1c in diabetic patients with absence/presence of vascular complications.
Methods: Total of 100 subjects was enrolled in the study. Sample for glucose estimation and platelet indices were
collected and estimation were carried out by the auto-analyzers. The statistical evaluation is done using SPSS version
22. Student t- test was used for doing comparison between two variables namely HbA1c <7 and HbA1c ≥7 and
diabetics with vascular complications v/s without vascular complications.
Results: MPV, is significantly higher in patients with type -2 diabetes mellitus with HbA1C ≥7 and those with
vascular complications in comparison to patients having HbA1c <7 and those without vascular complications ( p-
value <0.001 which is highly significant).
Conclusions: MPV might be used as a simple and cost-effective laboratory test in the follow up of diabetes mellitus
along with HbA1c and thereby help to reduce the morbidity and mortality.

Keywords: Diabetic mellitus, Mean platelet volume, Vascular complications

INTRODUCTION population, with equal rates in both men and women.

Mostly involve people with an age group of 40 to 59
Diabetes Mellitus is a global pandemic disease. It is a years. Diabetes at least doubles the risk of death.5 India is
chronic metabolic syndrome principally characterized by having highest burden of the diabetic subjects. A majority
persistent hyperglycemic.1 Impaired fasting glucose is of patients with type 2 DM, as well as subjects with IGT,
probably a frequent glycemic disorder in the general have signs of the metabolic syndrome (also called
population and is considered as a pre-diabetic state.2 As dysmetabolic syndrome, insulin resistance syndrome or
of 2014 estimated 387 million people have diabetes syndrome X), which is a cluster of phenotypes associated
worldwide.3 Diabetes caused 4.9 million deaths in 2014. with a substantially increased risk for cardiovascular
Every seven seconds a person dies from diabetes with disease (CVD). Insulin resistance plays a central role in
type 2 diabetes making up about 90% of the cases. The this syndrome. Other components are centripetal obesity,
incidence of DM is increasing, and will be more than hypertension, dyslipidemia (low HDL, high TG, small
doubled within 15 years mainly due to adverse life style dense oxidized LDL) and endothelial dysfunction
changes with excess in caloric intake and reduced (microalbuminuria).6 Recently, a prothrombotic state,
physical activity.4 This is equal to 8.3% of the adult characterized by abnormalities in platelet function and

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 Dubey I et al. Int J Res Med Sci. 2017 Mar;5(3):1042-1047

elevated circulating levels of C-reactive protein (CRP), 63 with increasing availability of blood cell analyzers
PAI-1 and fibrinogen, has been recognized as a related to platelets are being estimated most important
component of the metabolic syndrome. Microvascular parameters among them are platelet count, platelet
complications (retinopathy, nephropathy and neuropathy) distribution width / and mean platelet volume, the most
contribute importantly to the increased morbidity in DM commonly used measure of platelet size is a potential
as retinopathy and nephropathy are major causes of markers of platelet reactivity.17-19 It’s a new emerging
blindness and end-stage renal disease, respectively. risk factor for atherosclerosis.20 Patient with larger
However, the major cause of morbidity and mortality in platelets can be easily identified during routine
DM is macrovascular complications. More than 75% of hematological analysis and could possibly benefit from
all diabetic patients die of CVD. Insulin resistance, IGT the treatment for predicting the possibility of impending
and overt type 2 DM are associated with an increased risk acute events.
for CVD and patients with type 2 DM have a 2-4 fold
increased risk for coronary artery disease and peripheral The average amount of sugar in the blood can be
arterial disease, and a 3-fold increased risk for stroke determined by measuring HbA1c level. It is an important
compared to non-diabetic subjects.7 measure of control of diabetes over the last 3 months.
Studies on the role of HbA1c indicate that, it reflects the
Diabetes also worsens early and late outcomes in acute average blood sugar concentration for an extended time
coronary syndromes and after coronary interventions. period and that it remains unaffected by the short term
There is now consensus that patients with DM without fluctuation in blood sugar levels .The determination of
previous myocardial infarction should be treated with HbA1c levels serve as a convenient and suitable test for
multifactorial interventions against modifiable risk evaluation of the adequacy of diabetic control in the
factors as aggressively as in non-diabetic individuals with prevention of various diabetic complications. It is
a previous myocardial infarction.8 Although type 2 DM is sensitive and a specific test for detecting undiagnosed
associated risk factors, the exact causes of the diabetes and at risk individuals or early diabetics.
substantially eased risk of suffering CVD are not fully
understood. Premature, accelerated macrovascular The risk of diabetic complications, such as diabetic
disease occurs both in type 1 and type 2 DM. Recent nephropathy and retinopathy, increases with poor
epidemiological studies indicate that type 1 DM is as metabolic control .In accordance with its function as an
great a risk factor for cardiovascular mortality and stroke indicator for the mean blood glucose level, HbA1c
as type 2 DM, and that these complications also can predicts the development of diabetic complications in
occur at a young age.9 diabetes patients.

Platelet function is of pathophysiological importance in METHODS

atherothrombotic disease and there is strong support for
platelet dysfunction with platelet hyper reactivity in both This comparative prospective study was conducted at the
type 1 and type 2 DM.10,11 It may be hypothesized that J.K Hospital associated with L.N Medical College and
platelets, acting in concert with the vascular endothelium, research centre, Bhopal during the period of one year.
leukocytes and coagulation, play a key role in the Diagnosis of diabetic patient was established using 2014
development of diabetic angiopathy. While platelet ADA Criteria.21
dysfunction is clearly involved in the pathogenesis of
macro angiopathy, the role of platelets in  A fasting plasma glucose of >126 mg/dl were
microangiopathy is less clear.12 The metabolic state that considered as diabetics.
accompanies DM may alter platelet and endothelial  HbA1C ≥ 6.5% (48mmol/mol) group.
function already in early stages of diabetic disease.
However, it is debatable whether antidiabetic treatment The totals of 100 subjects were enrolled in the study. The
and improved metabolic control can restore the observed diabetic group, was divided into two namely HbA1c<7
platelet hyperactivity in DM. In addition, studies of the and HbA1c≥7 and diabetics with and without vascular
effect of acute hyperglycemia on platelet function in complications respectively. Sample for glucose
patients with DM are sparse.13 estimation and platelet indices were collected in sodium
fluoride and tri-potassium salt of EDTA respectively.
The increased platelet activity is emphasized to play a Glucose estimation was carried out by the auto-analyzers
role in the development of vascular complications of the using enzymatic hexokinase oxidation reference method
metabolic disorder. Large platelets are hemostatically for plasma glucose levels. Estimation of HbA1C was
more active and are a risk factor for developing coronary done using auto analyzer (COBAS C III) which is based
thrombosis, leading to myocardial infarction.14 The on turbidimetric inhibition immunoassay for hemolyzed
prevalence of diabetic micro-vascular complication is whole blood. where as platelet indices were done by
higher in people with poor glycemic control and with collecting venous blood samples for complete blood
long duration of diabetes mellitus.15 An increased platelet count using automated blood cell count analyzers
activity has been reported in diabetics as demonstrated by (NIHON KOHDEN). All test were conducted within 1
increase in GPIIb/IIIa, Ib-IX and Ia/IIIa.16 CD62 and CD hour of sample collection. Informed consent was taken

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 Dubey I et al. Int J Res Med Sci. 2017 Mar;5(3):1042-1047

from all the subjects. 2 ml blood was collected in each and p<0.05 is considered statistically significant. Student
vial under aseptic precautions. All consenting non- t-test was used for doing comparison between two
diabetic subjects were included as control group. Patient variables namely HbA1c <7 v/s HbA1c ≥7 and diabetics
already diagnosed of type 2 diabetes and patient who with vascular complications v/s without vascular
came for routine check-up and were found to diabetes. complications. Bar diagram were used for graphical
Exclusion criteria includes subjects having anemia (<13 representation of this data.
gm% in males) and (12 gm% in females), malignancy,
chronic renal failure, cyanotic heart disease, RESULTS
inflammatory conditions (rheumatoid arthritis, S.L.E),
thrombocytopenia, hypo/hyperthyroidism, diabetic on Diabetic group was also divided into two groups on the
anti-platelet drugs such as aspirin and clopidogrel. bases of HbA1C value. Group 1 with HbA1C level less
than 7% and Group 2 with HbA1C level More than 7
Statistical analysis %.Out of 100 patients in the diabetic group 10 patients
showed HbA1c value to be less than 7 % and 90 patients
The statistical software namely statistical package for the showed HbA1C to be more than 7%. Fasting plasma
social sciences (SPSS) version 22 is used for analysis of glucose was significantly raised in group 2 with HbA1C
data. Analysis of variance (ANOVA) is used to compare ≥7%. FPG in group 1 and 2 were 142.55±5.31 mg/dl and
the variables. Data is expressed as mean±standard 177±22.27 mg/dl respectively, which was highly
deviation. The p-value was calculated for each parameter significant between the two groups with p-value 0.000.

Table 1: Comparing the various parameters in two groups of diabetic patients with reference to HbA1c level.

Parameters HbA1C less than HbA1C more Statistical

p-value t-value
7(%) than 7 (%) Significance
10 90
Mean fasting plasma glucose
142.55±5.31 177.15±22.27 <0.0001 4.87 S
(mg/dl)
Mean platelet count (lacs/cumm) 2.44±0.65 2.70±0.79 0.3187 1.002 NS
Platelet distribution width (%) 17.2±0.80 18.6±10.35 0.0018 3.21 NS
Mean of mean platelet volume (fl) 7.87±0.540 9.06±1.72 0.0032 2.17 S
Duration of diabetes (Yrs) 6.4±3.39 6.36±3.68 0.970 0.033 NS

All the platelet indices (platelet count, MPV and PDW) However, PDW and platelet count does not show any
were found to be raised in group 2 with HbA1C ≥7 %. significance between two groups with p-value 0.3187 and
But value of MPV between the two groups shows 0.0018 respectively.
statistically significant difference in their value with p
value<0.0001. WITH VASCULAR COMPLICATION
WITHOUT VASCULAR COMPLICATION
12
R2 =0.306, R=593, p<0.00001
16 10
14
8
12
MPV(fl)

10 6
8
4
6
4 2
2
0
0 HbA1C
0 5 10
HbA1c 15 20

Figure 2: HbA1C of diabetic group with and without

Figure 1: Scatter plot showing positive correlation vascular complications. HbA1C was also found to be
between HbA1c and mean platelet volume (MPV). raised in diabetics with vascular complications.

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 Dubey I et al. Int J Res Med Sci. 2017 Mar;5(3):1042-1047

Platelet count in diabetics with complication was found to Though the count is slightly high in group with
be 2.86±0.76 lac/cumm in comparison to the platelet complication, two Groups shows no significant difference
count in diabetics without complications which was in the value of the platelet count. (p = 0.160 and t = 1.41).
2.61±0.78 lac/cumm.

Table 2: Comparisons of glycemic characteristics of diabetic patients with vascular complications and without
vascular complications.

With diabetic Without diabetic

Parameters vascular complication vascular complication p-value t-value Significance
N=26 N=74
FPG (mean±SD) mg/dl 190.80±24.21 168.51±20.39 <0.0001 4.56 S
HbA1C (%) 10.81±1.81 8.39±1.23 <0.0001 7.58 S

Value of mean Platelet Distribution width (PDW) does DISCUSSION

not show much difference in the two groups. And
statistically they are not significant (p=0.094 and t=1.69). The mean fasting plasma glucose level was found to be
190.80±24.21 mg/dl in diabetic patient with vascular
Table 3: Comparison of platelet indices in diabetic complications and fasting plasma glucose level in
patient with vascular complications and without diabetics without complication was found to be
vascular complications. 168.51±20.39 mg/dl. This shows that FPG was slightly
higher in group with vascular complications. Which is
With Without statistically significant with p value <0.0001(t-value
Param p- t-
vascular vascular 7.06).
eters value value
complication complication
Platelet The Mean platelet volume is 10.62±2.13 fl in diabetic
2.86±0.76 2.61±0.78 0.160 1.41
count* group with vascular complications which is found to be
PDW 17.93±0.81 18.70±11.55 0.094 1.69 raised in comparison to the group without vascular
MPV 10.62±2.13 8.40±1.00 <0.0001 7.06 complications.
N 26 74
*(LAC/CUMM) HbA1C was also found to be raised in diabetics with
vascular complications in comparison with diabetics
The Mean platelet volume is 10.62±2.13 fl in diabetic without vascular complications. HbA1C was
group with vascular complications which is found to be 10.81±1.81% and 8.39±1.23% respectively in the diabetic
raised in comparison to the group without vascular group with or without vascular complications. This
complications which is statistically significant with p difference in the value is significant (p <0.0001). Li S et
value <0.0001(t-value 7.06). al showed that the MPV level was highest in the type-2
DM group (12.3±1.5) fl.22 It was significantly higher in
WITH VASCULAR COMPLICATION diabetics with HbA1c ≥7% (13.2±1.9) fl than in patients
WITHOUT VASCULAR COMPLICATION those with HbA1c <7% (11.8±1.7) fl (p <0.01). Multiple
Logistic regression analysis indicated that MPV was an
20
18 important risk factor of peripheral arterial disease.
16
14 Demirtune R et al showed that MPV was significantly
12 higher in patients with DM than in controls (8.7±0.8 fl vs.
10 8.2±0.7 fl, p=.002).2 In diabetic patients, with vascular
8
6 complications there was a significant positive correlation
4 between MPV and HbA1c levels (r=0.39, P=.001) but not
2 in the diabetic group without vascular complications.
0 When they compared the two diabetic groups, Group B
PLATELET PDW MPV (HbA1c >7) patients had significantly higher MPV than
COUNT Group A (HbA1C <7) (9.0±0.7 fl vs. 8.4±0.8 fl, p=0.01)

If vascular damage was only due to increased number of

Figure 3: Comparison of mean platelet parameters large and reactive platelets, then the rate of damage
with complication and without complication in the would have been constant for the duration of disease and
diabetic group. independent of diabetic control. This clearly shows that

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Platelet reactivity alone cannot explain the progression of therefore there finding were limited as compared to a
vascular complication in diabetes mellitus, since there are study which includes pre diabetic patients (I.F.G).
other vascular risk factors that may be influenced by
degree of control of diabetes. This is supported by non- There was also a significant association between HbA1c
significant statistical correlation between MPV and and MPV, Which was again seen in study done by
duration of diabetes in our study. Microvascular Demirtune et al.2 Therefore, it may be concluded that
complications (retinopathy, nephropathy and neuropathy) glycemic control improves platelet activity and function
contribute importantly to the increased morbidity in DM and may prevent or delay the possible diabetic vascular
as retinopathy and nephropathy are major causes of complications. Study done by Kodiatte TA et al showed
blindness and end-stage renal disease, respectively. the similar finding that in diabetes mellitus mean platelet
However, the major cause of morbidity and mortality in volume (MPV) is increased and had a positive correlation
DM is macrovascular complications. More than 75% of with HbA1c Ulutas KT et al (2014).1,27 In this study, all
all diabetic patients die of CVD. Insulin resistance, IGT diabetic patients were divided into two groups according
and overt type 2 DM are associated with an increased risk to their HbA1c levels: group A consisted of patients with
for CVD and patients with type 2 DM have a 2-4 fold HbA1c levels ≤7% and group B consisted of patients
increased risk for coronary artery disease and peripheral with HbA1c levels >7%. Concluding that MPV was
arterial disease, and a 3-fold increased risk for stroke significantly higher in Group B as compared to both non-
compared to non-diabetic subjects. Diabetes also worsens diabetics and Group A. MPV had a high positive
early and late outcomes in acute coronary syndromes and correlation with HbA1c and FSG, as with diabetes
after coronary interventions.6,7 duration. It is found that MPV was increased in type 2
DM. Ozder found that patient with diabetes and subjects
Platelet in diabetes mellitus have dysregulated signaling with IFG,MPV was significantly higher (10.66±0.94 fl
pathway that lead to an increased activation and and 10.49±0.96 fl, respectively) as compared to the non-
aggregation in response to a given stimulus, thus diabetic group (10.04±1.04 fl) (p=0.000).24 Among the
triggering thrombus formation and causing diabetic group, a positive statistical correlation Pearson
micropapillary embolization with release of constrictive correlation was seen between MPV and HbA1c levels
,oxidative and mitogenic substances such as PDGF and (r=0.357;p=0.000) and fasting blood glucose levels (r=
VEGF that accelerate progression of local vascular lesion 0.306; p=0.0000.The mean MPV in patients having
like the neovascularization of lens in diabetic HbA1c <7.5 % was 10.17± 0.83 fl and significantly lower
retinopathies.23 Diabetic group was also divided into two than that of patients with HbA1c ≥ 7.5 % (10.30± 0.92 fl)
groups on the bases of HbA1C value. Group 1 with (p=0.001). Our findings suggested an association between
HbA1C level less than 7% and Group 2 with HbA1C MPV and HbA1c.Therefore, MPV would be a beneficial
level More than 7%. Out of 100 patients in the diabetic prognostic marker of cardio-vascular complications.
group 10 patients showed HbA1c value to be less than
7% and 90 patients showed HbA1C to be more than 7%. CONCLUSION
Fasting plasma glucose was significantly raised in group
2 with HbA1C ≥7%. FPG in group 1 and 2 were Most of the patient with type II DM suffers from
142.55±5.31 mg/dl and 177±22.27 mg/dl respectively, preventable vascular angiopathies and early diagnosis of
which was highly significant between the two groups progressive activation of coagulation can help manage
with p-value 0.0001. All the platelet indices (platelet these vascular diseases successfully. Therefore, MPV and
count, MPV and PDW) were found to be raised in group HbA1c can be a useful as prognostic marker of cardio-
2 with HbA1C ≥7%.But value of MPV between the two vascular complication in diabetics .MPV might be used
groups shows statistically significant difference in their as a simple and cost – effective laboratory test in the
value with p value <0.0001.However ,PDW and platelet follow up of DM along with HbA1c and thereby help to
count does not show any significance between two reduce the morbidity and mortality.
groups with p-value 0.3187 and 0.0018 respectively.
Funding: No funding sources
Ozder A also compared the platelet count between the Conflict of interest: None declared
two groups and does not found much difference between Ethical approval: The study was approved by the
the two groups.24 The mean Platelet count in two groups Institutional Ethics Committee
were 242.66±57.30 and 254.98±74.66 with p value 0.339
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