Utility of Platelet Indices in Assessing the Risk of Coronary Artery Disease in Patients of Diabetes Mellitus

Background: Platelet volume indices (PVI) such as mean platelet volume (MPV), platelet distribution width (PDW) and platelet large cell ratio (P-LCR), are the indicators of increased platelet activity which may play a role in development of vascular complications in diabetic patients. This study was performed to evaluate and compare the platelet volume indices such as MPV, PDW, P-LCR in patients of type 2 diabetes mellitus (DM) with and without manifested coronary artery disease in order to identify their usefulness in determining the risk for development of coronary complications. Methods: Analytical cross - sectional study included 150 patients of which 100 patients were diagnosed as type 2 DM and 50 apparently healthy controls. The study cases were divided into two groups based on presence or absence of coronary artery disease. Group A included 50 cases of type 2 DM without manifested coronary artery disease and group B included 50 cases of type 2 DM with manifested coronary artery disease. PVI was obtained using automated cell counter. Results: MPV, PDW, P-LCR were signicantly higher in diabetics as compared to controls subjects (P < 0.001 for all). However, no statistically signicant difference was found between diabetics with and without manifested coronary artery disease. Conclusions: The study showed higher PVI in diabetic subjects when compared to control subjects, but no difference between patients with and without manifested coronary artery disease suggesting that various other factors might be associated with the pathogenesis of CAD in patients of DM.


Introduction
Diabetes mellitus (DM) is a pandemic disease and most challenging problem in today's world. [1] It is considered as a "prothrombotic state" owing to sustained hyperglycemia, dyslipidemia and insulin resistance causing endothelial and pericyte injury. Altered platelet morphology have been observed in diabetes in the form of enhanced platelet activity. [2] Patients with type 2 DM have increased risk of developing cardiovascular disease (CVD). Moreover, CVD is one of the major cause of mortality in diabetic patients. Platelet activation plays an important role in the initiation and progress of atherothrombosis. [3] Larger platelets contain denser granules and are metabolically and enzymatically more active and produce more thromboxane A2. [4,5] Hence, MPV and PDW might help in assessing thrombotic risk whereas, P-LCR can give the measure for proportion of larger platelets.
In the present study we assessed the platelet indices in patients of diabetes mellitus with and without CAD and compared it with normal controls in order to identify its association in pathogenesis of CAD.

Subjects And Methods
Present study was analytical cross-sectional study. A total of 150 subject were included out of which study cases having DM (n=100) and control subjects (n=50) from July 2018 to May 2019. All the consecutive cases of T2DM who came to our hospital were included in the study. Patients having history suggestive of in ammatory conditions such as rheumatoid arthritis were excluded from the study.
The study cases were divided into two groups based on absence or presence of coronary artery disease as group A and B respectively. Group A included 50 cases of T2DM without manifested CAD and group B included 50 cases of T2DM with manifested CAD. Controls included 50 apparently healthy individuals without history of diabetes mellitus or coronary artery disease. Diabetics were diagnosed based on American Diabetes Association criteria of random blood glucose levels ≥200 mg/dl. The parameters which were obtained were analyzed using IBM SPSS 23.0 (ARMONK, NY, USA). Statistical test such as Student t test, Mann Whitney U test were used for nding the signi cant difference between two groups. Kruskal Wallis Test was used for nding signi cant difference between cases and controls. P value of < 0.05 was taken to be statistically signi cant. [6,7]

Results
Mean random blood glucose of group A was 189.94 ± 104.15 mg/dl, group B was 179.18 ± 70.95 mg/dl and control group was 93.54 ± 11.64 mg/dl which was statistically signi cant (p value <0.001, Student-t Test, Table 1) Comparison of HbA1c between cases and control which was statistically signi cant (p value < 0.001, Student-t Test) is shown in Table 1.
It was observed that the mean of NT-proBNP was higher in group B when compared to group A with p value < 0.05 as shown in Table 2.
Hypertension was seen in 22 out of 50 patients in group A and 39 out of 50 patients in group B. There was signi cant association p value < 0.05 between hypertension and presence of coronary artery disease in patients with diabetes mellitus as shown in Table 3.
The mean age of group A was 50.36 years (± 10.5 years), compared to group B which was 58.64 years (± 9.08 years). Platelet count and platelet volume indices were compared between cases (group A and group B) and controls.
Mean platelet count of the control group (298.08 ± 56.34 x 10 3 /µl) was higher as compared to group A (240.40 ± 106.25 x 10 3 /µl, p value < 0.001) and group B (256.28 ± 98.47 x 10 3 /µl, p value < 0.003) which was statistically signi cant. However, the difference between mean among group A and group B was statistically insigni cant with p value of 0.255. [ Table 4] The platelet indices including MPV, PDW and P-LCR also showed signi cant statistical difference between cases and controls p value < 0.001, but there was no statistically signi cant difference between group A and group B respectively. [ Table 4]

Discussion
In our study, we found that the platelet count was decreased in the diabetic subjects compared to controls, however no statistical signi cance was observed in diabetes with and without coronary artery disease.
In the present study, there was a signi cant difference in the platelet indices compared between cases and control but no signi cant difference of indices between diabetes with and without complications.
MPV is a parameter to assess the platelet size, and is an indicator of platelet reactivity. It has been seen that the larger platelets are more reactive than the smaller platelets. [8,9] In our study, MPV was signi cantly higher in diabetic subjects when compared to controls. Similar results were seen in other studies conducted by Shilpi et al and Pujani et al. [10,11] MPV was not signi cant between group A and group B results of which were similar to studies conducted by Jindal S et al [12] and Shilpi et al [11] but in discordance with other studies done by Kodiatte et al [8] which showed higher MPV in diabetic patients with complications.
In the present study, the platelet distribution width (PDW) was signi cantly higher in diabetics subjects when compared to controls, similar results was seen with the study conducted by Dindar et al. [13] The difference between PDW of group A and group B was insigni cant which was similar to studies conducted by Dubey I et al and Shilpi K et al, but in discordance with other studies. [1,10,11,14] In addition, P-LCR was also found to be higher in diabetics when compared to control subjects similar to other studies. [1,12] However, in the present study the difference of P-LCR between group A and group B was insigni cant which was in accordance with other studies but in discordance with some studies. [2, 8-10, 12, 15] The discordance which was seen in our study may be due to the fact that the patients with coronary complications (group B) were on antiplatelet therapy. B-type natriuretic peptide (BNP), cardiac hormone, and its N-terminal fragment (NT-proBNP) are synthesized and secreted from the ventricular myocardium. These markers are seen to be elevated in patients of acute coronary syndromes due to ventricular dysfunction.
In our study, NT-proBNP was found to be statistically signi cant in diabetic patients with coronary artery disease.
Cardiovascular disease is the most common cause of morbidity and mortality in adults. The major risk factors include arterial hypertension and diabetes. In the present study, we found a signi cant correlation between hypertension and presence of coronary artery disease in patients with diabetes mellitus.
Diabetes and hypertension often occur together as they share some common risk factors such as obesity and insulin resistance. The presence of hypertension in diabetic patients increases the risk for coronary artery disease.

Limitations of the study
The study had obvious limitations which was a small sample size and also was not multifactorial which would help in comparing the platelet volume indices and other pathological and clinical parameters such as lipid pro le, homocysteine, obesity, BMI, smoking etc.

Conclusion
In conclusion, the results of present study have shown that the platelet count and the platelet volume indices such as Mean platelet volume, Platelet distribution width, Platelet large cell ratio were found to be altered in patient of diabetes mellitus when compared to normal healthy controls. The study also indicated that the platelet volume indices were not different between the patients of diabetes mellitus with and without manifested coronary artery disease.
We found signi cant association between hypertension and manifested coronary artery disease in diabetic subjects, suggesting that various other factors might be associated with pathogenesis of coronary artery disease in patients of diabetes mellitus.
We suggest that a larger study should be conducted to identify the role of platelet indices various in the pathogenesis of coronary complication in patients of diabetes mellitus keeping in mind the multiple co variables in pathogenesis of DM and CAD.

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Ethics approval and consent to participate: The study was approved by the Ethical committee of our institute. Written informed consent was take from the participants before participating in the study.