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Evaluation of mean platelet volume and other platelet parameters in subjects with Type-2 diabetes mellitus.

INTRODUCTION

Diabetes mellitus (DM) is a metabolic disorder that affects more than 285 million people in the world and an estimated 439 million adults by 2030. [1] The risk of premature cerebral, coronary, and peripheral vascular disease and thrombotic events in subjects with Type-2 DM is increased 2- to 4-fold, and these vascular lesions can be life-threatening. [2]

In addition to cardiovascular disease, the prognosis of the patients with diabetes during major ischemic vascular events is poorer when compared to the non-diabetic. In the diabetics, the balanced normal hemostasis is shifted to favor thrombosis. Platelets from subjects with diabetes show hyper-reactivity (i.e., easily triggered by a stimulus) which may play a pivotal role in the development of diabetic complications. [3] Mean platelet volume (MPV) is a reliable index of platelet size. MPV correlates well with the functional status of platelets. It can be used as an emerging risk marker of platelet activation. An increased MPV, which is an indicator of hyper-reactive platelets, may result from an increased platelet turnover. It may, therefore, represent a risk factor for overall vascular mortality such as myocardial infarction. Some studies have reported the relationship between MPV and DM. The MPV can be measured by hematology analyzers. The aim of our study was to compare the platelet parameters between the subjects with diabetes and controls and to determine the effect of glycemic status and the duration of diabetes on the platelet parameters.

MATERIALS AND METHODS

In this cross-sectional study, we included 100 subjects with Type 2 diabetes mellitus as study group and 100 non-diabetic subjects as controls, all in the age range of 30-60 years. The subjects were recruited from the Diabetology Outpatient Department, Medicine Department and Master Health Checkup scheme, SRM Medical College and Hospital. Institutional Ethical Committee approval and permission obtained. Written informed consent was obtained from all the subjects. All the subjects underwent a complete clinical examination. The height and weight of the subjects were recorded. Subjects suffering from coagulation disorder, hyperlipidemia, hypertension, peripheral vascular disease, chronic renal disease, any debilitating illness, those who are on antiplatelet medications and those with the habit of smoking, tobacco chewing, and alcohol intake were excluded from the study.

After an overnight fasting, the following tests were undertaken: Blood pressure examination to rule out hypertension, estimation of the serum lipid profile to rule out hyperlipidemia, evaluation of the fasting, postprandial blood glucose levels, glycosylated hemoglobin (HbA1c), and platelet parameters such as platelet count (PLT), plateletcrit (PCT), MPV, platelet distribution width (PDW), and platelet-large cell ratio (P-LCR) were estimated using Sysmex II Autoanalyzer. MPV was calculated by the following formula: MPV (fL) = [(PCT (%)/platelet count (x[10.sup.9]/1)] x [10.sup.5]. PCT was the ratio of the platelet volume to the whole blood volume. PDW and P-LCR were analyzed from a histogram of platelet size distribution. The distribution width at the level of 20% (the peak of the histogram is 100%) was defined as PDW, and the percentage of platelets with a size of more than 12 fL was defined as P-LCR. [4]

To assess the relationship between glycemic control and platelet parameters, the diabetic subjects were divided into two groups according to their HbAlc levels: With HbAlc levels <7% (n = 56) and with HbAlc levels >7% (n = 44). We selected this cutoff point because it is usually selected in clinical practice to discriminate between appropriate and inappropriate control. [5]

To determine the effect of duration of diabetes on platelet parameters, the diabetic subjects were divided into two subgroups: One with diabetes duration <10 years (n = 61) and another group with diabetes duration >10 years (n = 11).

All the results of laboratory investigations were loaded in computerized SPSS 16 programer, and statistical significance was analyzed by unpaired Student's t-test. Results were expressed as mean [+ or -] standard deviation. The P < 0.05 has been considered as significant.

RESULTS

The anthropometric parameters between controls (Group I) and diabetics (Group II) were compared and shown in Table 1. Table 1 shows that there is no significant difference between the two groups. Table 2 compares the platelet parameters between the two groups and shows a statistically significant increase in MPV in diabetics. Table 3 compares the platelet parameters between the diabetics with HbA1c [less than or equal to]7 and HbA1c >7 and shows that the MPV and PDW were significantly increased in diabetics with HbA1c >7. Table 4 compares the platelet parameters between the diabetics with diabetic duration <10 years and those with diabetic duration >10 years and shows that MPV was significantly increased in diabetics with duration of the disease >10 years.

DISCUSSION

In our study, we compared platelet parameters between 100 diabetic subjects and 100 non-diabetic controls. Table 1 shows that there is no significant difference in the anthropometric data between the two groups, and the two groups were comparable. Our study has several important findings. Table 2 shows that all the platelet parameters were increased in Group II (diabetics) when compared to the controls, but only the increase in MPV in the diabetics was statistically significant. The results of our study were consistent with results of Kodiatte et al., [6] Papanas et al., [7] Sharpe and Trinick, [8] etc.

In our study, the mean platelet count in the diabetic group was higher than the non-diabetic group but not statistically significant, but in the study by Demirtunc et al., [9] the mean platelet count in the diabetic group was significantly higher than that of the non-diabetic group.

In our study, MPV and PDW were significantly higher in the diabetics with HbA1c >7% when compared to diabetics with HbA1c [less than or equal to]7% as shown in Table 3. This agreed with the findings of the studies done by Kodiatte et al. [6] and Zuberi et al. [10]

The larger platelets being hyper-reactive produce more prothrombotic factors. Platelet activation causes changes in platelet morphology and formation of pseudopodia. The enlarged platelets with lots of pseudopodia differ in the size, possibly affecting the platelet distribution. In our study, there is a significant increase in both MPV and PDW in diabetic subjects with poor glycemic control which shows platelet hyperactivity. Our results are similar to the results of Jindal et al. [11] According to Bancroft et al., [12] these changes in platelet show a disturbed hemostatic system and prothrombotic state in DM.

Due to hyperglycemia, the proteins on the surface of the platelets undergo non-enzymatic glycation which decreases platelet membrane fluidity and increases platelet reactivity. [13] In hyperglycemic conditions, the osmotic effect of glucose can also increase platelet reactivity. [14] There is increased expression of the surface glycoproteins Ib and IIb/IIIa in subjects with diabetes which mediate platelet adhesion and adherence and studies have shown that the expression of these adhesion proteins correlates with hyperglycemia indicated by HbA1c levels. [15] Furthermore, hyperglycemia increases the production of glycoproteins by megakaryocytes and promotes platelet activity. [16]

We also found that the MPV was significantly increased in diabetics with diabetic duration >10 years as shown in Table 4 which was in contrast to study result of Kodiatte et al., who showed no association between MPV and duration of diabetes. Yenigun et al. [17] found increased MPV in diabetics but no association between MPV and HbA1c, fasting blood glucose, patient age, and duration of diabetes.

In patients with Type-2 diabetes, the diabetic duration is independently associated with the risk of macrovascular and microvascular complications. [18] Yeom et al. [19] had found that the longer diabetic duration causes endothelial dysfunction resulting in high platelet aggregation and variations in hemorheological properties.

Poor glycemic control and longer duration of DM may lead to increased morbidities and mortalities in DM and studies [9,20] have shown that glycemic control may prevent or delay possible diabetic vascular complications by improving platelet activity and function. Thus, MPV can be used as a useful prognostic marker and a simple, economical tool to monitor the progression and control of DM and thus in preventing complications in primary health care.

CONCLUSION

Our study shows increased MPV in subjects with diabetes when compared with non-diabetics and that an increase in HbA1c concentration, which indicates poor glycemic control, was accompanied by increased MPV and PDW values. Longer duration of diabetes also increases the MPV. As the diabetic subjects have higher baseline platelet reactivity, assessment of MPV, a simple and cost-effective laboratory test would be a useful prognostic marker of cardiovascular complications in diabetes and thereby help hold the morbidity and mortality.

REFERENCES

[1.] Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4-14.

[2.] Laakso M, Lehto S. Epidemiology of risk factors for cardiovascular disease in diabetes and impaired glucose tolerance. Atherosclerosis. 1998;137 Suppl: S65-73.

[3.] Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Sabate M, Jimenez-Quevedo P, et al. Platelet function profiles in patients with Type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes. 2005;54:2430-5.

[4.] Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E, et al. Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol. 2005;128:698-702.

[5.] Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical management of hyperglycemia in Type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203.

[6.] Kodiatte TA, Manikyam UK, Rao SB, Jagadish TM, Reddy M, Lingaiah HK, et al. Mean platelet volume in Type 2 diabetes mellitus. J Lab Physicians. 2012;4:5-9.

[7.] Papanas N, Symeonidis G, Maltezos E, Mavridis G, Karavageli E, Vosnakidis T, et al. Mean platelet volume in patients with Type 2 diabetes mellitus. Platelets. 2004;15:475-8.

[8.] Sharpe PC, Trinick T. Mean platelet volume in diabetes mellitus. Q J Med. 1993;86(11):739-42.

[9.] Demirtunc R, Duman D, Basar M, Bilgi M, Teomete M, Garip T. The relationship between glycemic control and platelet activity in Type 2 diabetes mellitus. J Diabetes Complications. 2009;23(2):89-94.

[10.] Zuberi BF, Akhtar N, Afsar S. Comparison of mean platelet volume in patients with diabetes mellitus, impaired fasting glucose and non-diabetic subjects. Singapore Med J. 2008;49:114-6.

[11.] Jindal S, Gupta S, Gupta R, Kakkar A, Singh HV, Gupta K, et al. Platelet indices in diabetes mellitus: Indicators of diabetic microvascular complications. Hematology. 2011;16(2):86-9.

[12.] Bancroft AJ, Abel EW, Mclaren M, Belch JJ. Mean platelet volume is a useful parameter: A reproducible routine method using a modified Coulter thrombocytometer. Platelets. 2000;11:379-87.

[13.] Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in Type 2 diabetes. Diabetes Care. 2001;24(8):1476-85.

[14.] Schneider DJ. Factors contributing to increased platelet reactivity in people with diabetes. Diabetes Care. 2009;32(4):525-7.

[15.] Winocour PD. Platelets, vascular disease, and diabetes mellitus. Can J Physiol Pharmacol. 1994;72(3):295-303.

[16.] Kakouros N, Rade JJ, Kourliouros A, Resar JR. Platelet function in patients with diabetes mellitus: From a theoretical to a practical perspective. Int J Endocrinol. 2011;2011:742719.

[17.] Yemgun EC, Okay GU, Pirpir A, Hondur A, Yildirim IS. Increased mean platelet volume in Type 2 diabetes mellitus. Dicle Tip Dergisi. 2014;41:17-22.

[18.] Zoungas S, Woodward M, Li Q, Cooper ME, Hamet P, Harrap S, et al. Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in Type 2 diabetes. Diabetologia. 2014;57(12):2465-74.

[19.] Yeom E, Byeon H, Lee SJ. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats. Sci Rep. 2016;6:21913.

[20.] Ozder A, Eker HH. Investigation of mean platelet volume in patients with Type 2 diabetes mellitus and in subjects with impaired fasting glucose: A cost-effective tool in primary health care? Int J Clin Exp Med. 2014;7(8):2292-7.

How to cite this article: Anandhalakshmi S, Kalaivani A, Shivasekar G, Saravanan A. Evaluation of mean platelet volume and other platelet parameters in subjects with Type-2 diabetes mellitus. Natl J Physiol Pharm Pharmacol 2017;7(1):51-54.

Source of Support: Nil, Conflict of Interest: None declared.

Anandhalakshmi Swaminathan (1), Kalaivani Amitkumar (2), Shivashekar Ganapathy (2), Saravanan Ayyavoo (1)

(1) Department of Physiology, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur, Tamil Nadu, India, (2) Department of Pathology, SRM Medical College Hospital and Research Centre, SRM University, Kattankulathur, Tamil Nadu, India

Correspondence to: Anandhalakshmi Swaminathan, E-mail: dranandhalakshmismd@gmail.com

Received: July 02, 2016; Accepted: July 18, 2016

DOI: 10.5455/njppp.2016.6.0719518072016
Table 1: Comparison of physical characteristics between controls and
diabetics

Variables    Group I            Group II           t value  P value
             control            diabetics
             (n=100)            (n=100)

Age (years)  48.1[+ or -]6.116  49[+ or -]7.34     0.956    0.34
Height (m)    1.65[+ or -]0.11   1.66[+ or -]0.13  1.812    0.072
Weight (kg)  63.4[+ or -]8.8    64.4[+ or -]11.5   1.82     0.07
BMI          23.51[+ or -]3.2   23.7[+ or -]3.37   0.101    0.9204

Statistically significant. SD: Standard deviation, BMI: Body mass index

Table 2: Comparison of platelet parameters between controls and
diabetics

Platelet    Mean[+ or -]SD                          t value  P value
parameters  Group I             Group II
            controls            DM
            (n=100)             (n=100)

PLT          2.741[+ or -]0.47   3.010[+ or -]0.81  1.748   0.0837
PDW         11.729[+ or -]0.86  11.988[+ or -]1.78  0.682   0.496
MPV          9.816[+ or -]0.4   10.2[+ or -]0.77    2.299   0.023 (*)
P-LCR       25.50[+ or -]2.98   26.366[+ or -]5.43  0.730   0.46
PCT          0.27[+ or -]0.04    0.294[+ or -]0.07  1.586   0.11

(*) Statistically significant. SD: Standard deviation, PLT: Platelet
count, PDW: Platelet distribution width, MPV: Mean platelet volume,
P-LCR: Platelet-large cell ratio, PCT: Plateletcrit, DM: Diabetes
mellitus

Table 3: Comparison of platelet parameters between diabetics with HbA
[less than or equal to] 7 and HbA1c >7

Platelet
parameters  Mean[+ or -]SD                       t value  P value
            Diabetics with    Diabetics with
            HbAlc <7 (n=56)   HbAlc >7 (n=44)

PLT          2.92[+ or -]0.7   3.09[+ or -]0.84  -0.83    0.41
PDW         11.37[+ or -]1.0  12.42[+ or -]1.48  -2.67    0.01 (*)
MPV         10.01[+ or -]0.7  10.54[+ or -]0.85  -2.73    0.008 (*)
P-LCR       26.04[+ or -]5.1  26.73[+ or -]5.74   0.49    0.62
PCT          0.29[+ or -]0.0   0.3[+ or -]0.09   -0.57    0.56

(*) Statistically significant. SD: Standard deviation, PLT: Platelet
count, PDW: Platelet distribution width, MPV: Mean platelet volume,
P-LCR: Platelet-large cell ratio, PCT: Plateletcrit

Table 4: Comparison of platelet parameters between diabetics with
diabetic duration [less than or equal to]10 years and >10 years

Platelet
parameters  Mean[+ or -]SD                          t value  P value
            Duration of          Duration of
            diabetes           diabetes >10
            [less than or        years (n=39)
            equal to]10
            years (n=61)

PLT          2.88[+ or -]0.83    2.93[+ or -]0.79     -0.19   0.85
PDW         11.56[+ or -]1.33   12.27[+ or -]1.62  -1051      0.13
MPV         10.20[+ or -]0.76   10.65[+ or -]0.7      -2.09   0.04 (*)
P-LCR       27.14[+ or -]4.68   27.28[+ or -]5.94      0.55   0.58
PCT          0.28[+ or -]0.06    0.30[+ or -]0.08     -0.75   0.45

(*) Statistically significant. SD: Standard deviation, PLT: Platelet
count, PDW: Platelet distribution width, MPV: Mean platelet volume,
P-LCR: Platelet-large cell ratio, PCT: Plateletcrit
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Title Annotation:RESEARCH ARTICLE
Author:Swaminathan, Anandhalakshmi; Amitkumar, Kalaivani; Ganapathy, Shivashekar; Ayyavoo, Saravanan
Publication:National Journal of Physiology, Pharmacy and Pharmacology
Date:Jan 1, 2017
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