A comparative study of platelet to lymphocyte ratio in diabetic and non-diabetic subjects
Shanthini R1, Abiramasundari R2, Dharani B3, Viji Devanand4, Subathra S5
1 Associate Professor, 2 Assistant Professor, 3 Post Graduate, 4 Professor & HOD, 5 Assistant Professor, Department of Physiology, Stanley Medical College, Chennai – 600 001, Tamil Nadu, India.
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Abstract
Background: Type 2 diabetes mellitus is the most common non-communicable disease worldwide. It is known as a progressive metabolic disease which arises because of insulin resistance and impaired insulin secretion. The hallmark of type 2 diabetes mellitus is its microangiopathic complications. Oxidative stress is a key factor in pathological processes which are observed in type 2 diabetes mellitus. Platelet to lymphocyte ratio might be increased in type 2 diabetes mellitus due to chronic inflammation. Aim: To compare the platelet-to-lymphocyte ratio in the Type 2 diabetic group and the control group.Materials and methods: A cross sectional analytical study was conducted with 30 healthy volunteers as the control group and 30 type 2 diabetic individuals as the study group.The complete blood count was done and the platelet to lymphocyte ratio was calculated as the ratio of the platelet count to absolute lymphocyte count.Results: The data obtained were analyzed using Statistical Package for Social Sciences (SPSS) version 20. The mean platelet to lymphocyte ratio in control group was 105.919±39.34 versus 132.192±42.01 in type 2 diabetic group and was found to be statistically significant (p-value <0.05). Conclusion: The present study found that platelet to lymphocyte ratio was high in diabetic subjects than in control subjects which is statistically significant (p-value <0.05). Hence, during routine checkup the platelet to lymphocyte ratio should be checked for assessing the disease severity and to prevent atherosclerotic complications in type 2 diabetes mellitus.
Key words: inflammation, platelet to lymphocyte ratio, type 2 diabetes mellitus
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Corresponding Author
Dr. R. Abiramasundari, Assistant Professor, Department of Physiology, StanleyMedical College,
Chennai – 600001, Tamil Nadu, India
Telephone: +91 9443724669E-mail: [email protected]
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Introduction
Type 2 diabetes mellitus is the most common non-communicable disease worldwide. It is known as a progressive metabolic disease which is due to insulin resistance and impaired insulin secretion. The hallmark of progressive form of type 2 diabetes mellitus is its microangiopathic complications. The clinical presentations of such microvascular complications include diabetic nephropathy, diabetic neuropathy and coronary artery diseasewhich are associated with chronic low grade systemic inflammation1.Oxidative stress is a key factor in pathological processes which are observed in type 2 diabetes mellitus2,3,4.
The level of oxidative stress in type 2 diabetes mellitus can be assessed by measuring circulating inflammatory biomarkers. The level of diabetes control can also be assessed by measuring various circulating inflammatory markers5. The platelet to lymphocyte ratio (PLR) is an important novel inflammatory biomarker. The PLR level can be assessed by routine hemogram. It is commonly employed in many diseases for assessing inflammation and prognosis. High platelet and low lymphocyte count are associated with adverse cardiovascular outcomes6.
Platelet to lymphocyte ratio is defined as the ratio of platelet count to absolute lymphocyte count7.Platelets release proinflammatory mediators such as chemokines and cytokines. Hence platelet to lymphocyte ratio might be increased in type 2 diabetes mellitus due to chronic inflammation. This increases the risk of cardiovascular events in type 2 diabetes mellitus8,9.
Hence inthis study, we have compared the level of platelet to lymphocyte ratio in diabetic and healthy subjects.
Aim and objectives
1. To assess the platelet-to-lymphocyte ratio in the Type 2 diabetic group.
2. To compare the platelet-to-lymphocyte ratio in the Type 2 diabetic group and the control group.
Materials and Methods
A cross sectional analytical study was conducted with 30 healthy volunteers as the control group and 30 type 2 diabetic individuals as the study group. The duration of study was 6 months.
Inclusion criteria
Type 2 diabetic individuals who fit into the World Health Organization diagnostic criteria of type 2 diabetes mellitus with fasting blood sugar ≥126mg/dl or postprandial blood glucose ≥200mg/dl or HbA1c ≥6.5%. The study participants belong to the age group of 30-50yrs and duration of diabetes mellitus ≤5 years.
Exclusion criteria
• Age <30yrs or >50yrs.
• H/O Chronic inflammatory disorder
• H/O smoking or tobacco chewing
• H/O hypertension
• BMI > 30.
• Pregnancy
Institutional Ethical Committee clearance was obtained. After giving complete information about the study, informed and written consent was obtained from the participants who were selected from Out Patient department of Diabetology. The participants were assured of the confidentiality. Using a validated semi structured proforma, a detailed history was obtained. A detailed clinical examination was done.
Under sterile precautions,2ml of venous blood sample was collected for complete blood count assessment. The complete blood count was done using SYSMEX automated complete blood count analyzer. The platelet to lymphocyte ratio was calculated as the ratio of the platelet count to absolute lymphocyte count.
Statistical analysis
The data obtained were analyzed by using Statistical Package for Social Sciences (SPSS) version 20. The comparisons of the variables among the study groups were done using student ‘t’-test.
Results
The data were analyzed and Mean and standard deviation was calculated for parameters like age, BMI, biochemical parameters and platelet to lymphocyte ratio for the control group and type 2 diabetic group. Comparison of the parameters among the study groups was done using student ‘t’test.
Table 1: Depicts the comparison of age, BMI, biochemical parameters and Platelet to Lymphocyte Ratio among the study groups. The mean age in the control group was 44±4.44 versus 44±5.13 in type 2 diabetic group. The mean BMI in the control group was 22±2.69 versus 22±2.25 in type 2 diabetic group. The p-value of age and BMI was not statistically significant. This shows that the study groups were age and BMI matched. The mean Platelet count in control group was 2.9631±0.81 versus 2.9631±0.814645 in type 2 diabetic group and was found to statistically significant (p-value <0.05).

Table 1: Comparison of age, BMI and biochemical parameters among the study groups
Variables Control group
(Mean±SD) (n=30)
Type 2 diabetes mellitus group
(Mean±SD) (n=30)
p-value
AGE (yrs) 44±4.44 44±5.13 0.1546
HEIGHT (cm) 157±4.98 157±3.87 0.2584
WEIGHT (Kg) 63±6.98 65±5.36 0.1565
BMI 22±2.69 22±2.25 0.2124
HbA1C (%) 4.3±0.49 6.2±0.36 0.0354*
FBS (mg/dl) 92±8.88 172±37.13 0.0006**
PPBS (mg/dl) 117±8.96 216±80.54 0.0008**
RBS (mg/dl) 115±6.53 210±69.25 0.0006**
Platelet Count (Lakhs/mm3) 2.9631±0.81 3.1355±0.69 0.0412*
Absolute Lymphocyte Count (cells/mm3) 3014±948.15 2469±632.69 0.0486*
Platelet to Lymphocyte Ratio 105.919±39.34 132.192±42.01 0.0124*
*-Significant **-Highly significant

The mean absolute lymphocyte count in control group was 3014±948.15 versus 2469±632.69 in type 2 diabetic group and was found to statistically significant (p-value <0.05). The mean platelet to lymphocyte ratio in control group was 105.919±39.34 versus 132.192±42.01 in type 2 diabetic group and was found to be statistically significant (p-value <0.05). Figure 1 depicts the comparison of platelet to lymphocyte ratio between control group and diabetic group It shows that platelet to lymphocyte ratio was high in diabetic subjects than in control subjects.

Figure 1: Comparison of Platelet to Lymphocyte ratio between control group and diabetic group

Discussion
The present study was undertaken to compare the platelet to lymphocyte ratio between diabetic and healthy subjects. In type 2 diabetes mellitus, the pathogenesis is an inflammatory process10. Type 2 diabetes mellitus is a chronic inflammatory disease which gets aggravated with poor diabetic control. Pradhan et al in their study found that rise in inflammatory markers such as IL-6 and CRP predicts the occurrence of type 2 diabetes mellitus11. It was also found that chronic inflammation was associated with high mortality risk in type 2 diabetes mellitus12. Navarro et al in their study found that inflammatory markers such as CRP and TNF alpha was closely associated with albuminuria in type 2 diabetes mellitus13.
Platelet to lymphocyte ratio (PLR) was studied as an inflammatory marker in various diseases. The role of platelets in inflammation was found to be due to its interaction with various cell types such as T-lymphocytes, dendritic cells, neutrophils, endothelial cells and phagocytes14. Akboga et al in their study found that platelet to lymphocyte ratio was associated with disease severity in coronary artery disease15.
Type 2 diabetes mellitus has been linked with platelet dysfunction16,17. The hormone insulin is a major antagonist of platelet hyperactivity. Insulin sensitizes the platelets to prostacyclins and also leads to increased generation of prostacyclins and nitric oxide from endothelium. This causes vasodilatation of smooth muscles and also prevents platelets adhesion and aggregation. Insulin also acts on monocytes and thereby exerts anti-inflammatory effects. It downregulates pro-aggregatory substances such as ADP, collagen and thrombin18. Impairment of several inflammatory pathways in type 2 diabetes mellitus leads to increased platelet reactivity19.In type 2 diabetes mellitus, platelets easily adhere and aggregate to endothelial cells16. The increase in platelet to lymphocyte ratio has been explained by increase in absolute platelet count in type 2 diabetes mellitus because of chronic systemic inflammation20.
Insulin resistance in type 2 diabetes mellitus is defined as a metabolic state in which for the apparently available insulin, the tissue response to insulin is less than the expected. Almer et al in their study found that elevated intravascular thrombin generation as well as decreased fibrinolytic potential in type 2 diabetes mellitus are the key contributors of atherosclerosis21. The low fibrinolytic activity in type 2 diabetes mellitus was found to be due to increased PAI-1 which prevents the formation of plasmin from plasminogen22. Festa et al in their study found that insulin resistance was associated with increased level of PAI-1 which acts as a link between coronary artery disease and insulin resistance23.Oxidative stress and inflammation in type 2 diabetes mellitus are associated with enhanced fibrinogen synthesis which promotes atherogenesis24. Increased fibrinogen levels in type 2 diabetes mellitus promotes platelet aggregation and fibrin clot formation25.Platelet to Lymphocyte ratio is said to be a major factor which emphasizes the interplay of two major components, thrombosis and inflammation in microangiopathy of type 2 diabetes mellitus26. Hence, Platelet to lymphocyte ratio predicts both inflammation and hyperactive coagulation in type 2 diabetes mellitus.
Our present study found that platelet to lymphocyte ratio was increased in type 2 diabetic individuals with duration of diabetes <5 years when compared to healthy individuals. This indicates that increased platelet to lymphocyte ratio is associated with increased systemic inflammation as well as disease severity. This shows that there is an increased risk of microangiopathy complications in early type 2 diabetes mellitus. Similar findings were observed in Burcin et al study5. Pickup and Jialal et al in their study showed that increased inflammation in type 2 diabetes mellitus was associated with development of complications27,28.
Ahmed et al in their study found that platelet to lymphocyte ratio was increased in diabetic nephropathy29.They found that endothelial dysfunction and inflammation in type 2 diabetes mellitus could be the underlying reason for diabetic nephropathy. Similar findings are present in our study. Demirtas et al in their study found that PLR levels were found to be independent predictor of diabetes and independent predictor of impaired glucose regulation in type 2 diabetic patients30.Zhang in their study found that platelet to lymphocyte ratio was elevated in diabetic foot ulcer due to underlying inflammation31. Similar findings are present in our study.
Conclusion
The present study found that platelet to lymphocyte ratio in type 2 diabetes mellitus was increased in type 2 diabetic group with duration of diabetes <5years when compared to normal group which is statistically significant (p-value<0.05). This shows that platelet to lymphocyte ratio can be used as an inflammatory marker to find out the disease severity in early type 2 diabetes mellitus. Hence, during routine checkup the platelet to lymphocyte ratio should be checked for assessing the disease severity as well to prevent atherosclerotic complications in type 2 diabetes mellitus.
Limitations
The present study has not assessed other inflammatory markers like CRP, Neutrophil to Lymphocyte ratio, Fibrinogen, Ferritin and TNF. Based on the findings from the current study, future studies on study of inflammation in type 2 diabetes mellitus can be done by assessing all the other inflammatory biomarkers.
Acknowledgements: Nil
Conflict of interest: Nil
References
1. Harris MI, Klein R, Welborn T A, Knuiman MW. Onset of NIDDM occurs at least 4-7 years before clinical diagnosis. Diabetes Care. 1992; 15: 815-819.
2. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ. Res. 2010; 107: 1058-1070.
3. Abdul-Ghani. MA, DeFronzo RA. Oxidative stress in type 2 diabetes mellitus. Oxidative stress in aging. 2008; 191-211.
4. Henriksen EJ, Diamond-Stanic MK, Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic. Biol. Med. 2011; 51: 993-999.
5. BurcinAtak, GulaliAktas, Tuba T Duman, EdipErkus, M ZahidKocak et al. Diabetes control could through platelet-to-lymphocyte ratio in hemograms. Rev Assoc Med Bras. 2018; 65(1): 38-42.
6. Mustafa Oylumlu, AbdukadirYildiz, Muhammed Oylumlu, Murat Yuksel, NihatPolat et al. Platelet to lymphocyte ratio is a predictor of in-hospital mortality patients with acute coronary syndrome. Anatol J Cardiol. 2015; 15: 277-283.
7. Sevket-Balta, CengizOzturk. The platelet-lymphocyte ratio: A simple, inexpensive and rapid prognostic marker for cardiovascular events. Platelets. 2014; 26(7): 680-681.
8. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest. 2005; 115: 3378-3384.
9. Lindemann S, Kramer B, Seizer P. Gawaz M. Platelets, inflammation and atherosclerosis. J ThrombHaemost. 2007; 1: 203-211.
10. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. NatRev Immunol. 2011;11(2):98-107.
11. Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Jama.2001;286(3):327-334.
12. Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, andindependently associated with risk of death. Diabetes. 2002;51(4):1157-1165.
13. Navarro JF, Mora C, Maca M, Garca J. Inflammatory parameters are independentlyassociated with urinary albumin in type 2 diabetes mellitus. AmJ Kidney Dis. 2003;42(1):53-61.
14. Borissoff JI, Spronk HM, Ten Cate H. The hemostatic system as a modulator of atherosclerosis. N. Engl. J. Med.2011; 364(18): 1746–1760.
15. Akboga MK, Canpolat U, Yayla C, Ozcan F, Ozeke O, Topaloglu S, et al. Association of platelet to lymphocyte ratio with inflammation and severityof coronary atherosclerosis in patients with stable coronary artery disease.Angiology. 2016;67(1):89-95.
16. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in Type 2 diabetes. Diabetes Care. 2001;24(8): 1476–1485.
17. Lekston A, Hudzik B, Hawranek M et al. Prognostic significance of mean platelet volume in diabetic patients with ST-elevation myocardial infarction. J. Diabetes Complications. 2014;28(5): 652–657.
18. Vinik AI, Erbas T, Park TS, Stansberry KB, Scanelli JA et al. Dermal neurovascular dysfunction in type 2 diabetes. Diabetes Care. 2001; 24: 1468–1475.
19. BartoszHudzik, JanuszSzkodzinski, JaroslawGorol, Jacek Niedziela, Andrzej Lekston et al. Platelet-to-lymphocyte ratio is a marker of poor prognosis in patients with diabetes mellitus and ST-elevation myocardial infarction. Biomark. Med. 2015; 9(3): 199-207.
20. Akinsegun A, AkinolaOlusola D, Sarah JO, Olajumoke O, Adewumi A, Majeed O, et al. Mean platelet volume and platelet counts in type 2 diabetes: mellitus on treatment and non-diabetic mellitus controls in Lagos, Nigeria.PanAfr Med J. 2014;18:42.
21. Almer L, Nilsson IM. On fibrinolysis in diabetes mellitus.Acta Med Scand. 1975; 198: 101–106.
22. Juhan-Vague I, Roul C, Alessi MC, Ardissone JP, Heim M et al. Increased plasminogen activator inhibitor activity in non-insulin-dependent diabetic patients: relationship with plasma insulin.ThrombHaemost. 1989;61:370 –373.
23. Festa A, D’Agostino R, MykkanenL,Tracy RP, Zaccaro DJ et al.Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance: The Insulin Resistance Atherosclerosis Study (IRAS). ArteriosclerThrombVasc Biol. 1999; 19: 562–568.
24. Udvardy M, Pfliegler G, Rak K.Plateletinsulin receptor determination in non-insulindependent diabetes mellitus. Experientia. 1985; 41:422– 423.
25. Banga JD, Sixma JJ. Diabetes mellitus, vascular disease and thrombosis. ClinHaematol. 1986; 15: 465– 492.
26. Grundy SM, Benjamin IJ, Burke GL,Chait A, Eckel RH et al. Diabetes andcardiovascular disease: a statement forhealth professionals from the AmericanHeart Association.Circulation. 1999; 100:1134–1146.
27. Jialal I, Devaraj S, Venugopal SK. Oxidative stress, inflammation, and diabetic vasculopathies: the role of alpha tocopherol therapy. Free Radic Res. 2002; 36(12): 1331-1336.
28. Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004; 27(3): 813-823.
29. Ahmed AteiaAbdelaziz, El-Sayed El-Meghawry El-Sayed, Tarek Mustafa Emran, Ali Ibrahim Abdallah. Study of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) as a predictor inflammatory marker for diabetic nephropathy in type 2 diabetic patients. The Egyptian Journal of Hospital Medicine. 2018; 72 (7): 4800-4807.
30. Demirtas L, Degirmenci H, Akbas EM. Association of hematological indicies with diabetes, impaired glucose regulation and microvascular complications of diabetes. International Journal of Clinical and Experimental Medicine.2015; 8(7):11420-11427.
31. Kuanxin Zhang, Sheng Ding, XiaoyuLyu,Qin Tan, Zhongjing Wang. Correlation between the platelet‐to‐lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus. J Clin Lab Anal. 2021; e23719