International Journal of Current Research and Review
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IJCRR - Vol 06 Issue 06, March, 2014

Pages: 20-25

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ASSOCIATION OF HbA1c WITH SERUM LIPID PROFILE AND LIPOPROTEIN (a) IN TYPE 2 DIABETES MELLITUS

Author: Mahantesh Patil, Nirmal Kumar, Aliya Nusrath, Shubha Jayaram, Rajeshwari A.

Category: Healthcare

Abstract:Background: Diabetes mellitus (DM) is a group of metabolic disorders of carbohydrate metabolism. Also it is proposed thatunderutilization of glucose is associated with changes in lipid profile. Lipoprotein (a) [Lp (a)] is regarded as an independent indicator of risk development of vascular disease which is also a diabetic complication. Changes in lipid profile are also well related with severity of DM as adjudged by glycated Hb (HbA1c). Objectives: The study intends to find the association between Lipid profile, Lp (a) and HbA1c levels in type 2 diabetic patients. Methods: A case-control study was conducted in Adichunchanagiri Institute of Medical Sciences, B.G.Nagara, Karnataka from 1st Jan to 15th June 2012. Study involved 80 participants of which 40 were patients admitted with diagnosis of DM and other 40 were healthy controls. Blood samples were collected in fasting state and analyzed for FBS, PPBS, HbA1c, TAG, VLDL, HDL, LDL and Lp(a) and values were tabulated for statistical evaluation. Results: In DM patientssignificant changes in the following parameters were observedcompared to controls. FBS, PPBS, HbA1c &Lp (a) levels increased significantly (P< 0.001), HbA1c/HDL, HbA1c/LDL & HbA1c/Chol ratios also increased significantly (P< 0.001). Also the levels of TAG, VLDL &Chol/HDL were significantly increased with P< 0.008, P< 0.011 & P< 0.003 respectively. The levels of HDL were significantly reduced in patients with DM compared to controls with P< 0.002. There is no significant change observed in Cholesterol, LDL & HbA1c/Lp (a) levels. Conclusions: Along with lipid profile and Chol/HDL ratio, study of HbA1c/HDL, HbA1c/LDL & HbA1c/Chol ratios may be helpful in risk assessment of coronary heart disease in DM and association between Lp (a) and HbA1c needs to be further evaluated.

Keywords: Diabetes Mellitus, Glycated hemoglobin (HbA1c), Lp (a)

Full Text:

INTRODUCTION

Diabetes mellitus (DM) is an iceberg disease. The metabolic dysregulation associated with DM causes secondary pathological changes in multiple organ systems that impose a tremendous burden on the individual with diabetes and on the health care system. In the United States, DM is the leading cause of end-stage renal disease (ESRD), no traumaticlower extremity amputations, and adult blindness. It also predisposes to cardiovascular diseases. With an increasing incidence worldwide, DM will be a leading cause of morbidity and mortality for the foreseeable future.[1]The number of adults with diabetes in the world will rise from 135 million in 1995 to 300 million in the year 2025. Presently, India, China, and the United States are the countries with the largest number of people suffering from diabetes and this trend is expected to continue till the year 2025,.[2, 3]In India alone, diabetes is expected to increase from 40.6 million in 2006 to 79.4 million by 2030.[4] Most of the longstanding macro and micro vascular complications are also more common among Indian diabetics as compared to other races and ethnic groups. Recent studies have shown that the prevalence of coronary heart disease (CHD) in Indian diabetics may be as high as in the migrant population. [4] Changes in lipid-profile are a consequential event in DM. Due to these changes distribution and function of various fractions of lipids are affected. Many Studies have evaluated the risk factors for CHD in DM patients and observed high fasting blood sugar (FBS) and post prandial blood sugar (PPBS), total cholesterol (Chol), low density lipoproteins (LDL), triglycerides (TAG) levels and low high density lipoproteins (HDL) levels when compared to controls. [5] Glycated heamoglobin (HbA1c) is considered a gold-standard measure of chronic glycemia in diabetic patients. In the Rancho Bernardo study, HbA1c was a better CHD predictor than fasting or 2-h glucose.[6]HbA1c was strongly associated with atherosclerosis as measured by carotid IMT (intima-media thickness). [7, 8]The ADA recommends measurement of HbA1c in patients with both type 1 and 2 diabetes, first to document the degree of glycemic control, then as part of continuing care.[9] Changes in lipid profile is also well related with severity of DM as adjudged by HbA1c. Lipoprotein (a) [Lp (a)] is a distinct class of lipoprotein that is structurally related to LDL, because both lipoprotein classes possess one molecule of Apo B-100 per particle and have similar lipid compositions. However, unlike LDL, Lp (a) contains a carbohydrate rich protein [Apo (a)]. Apo (a) is a unique component and has significant homology with plasminogen. [10] The serum level of Lp (a) is an independent indicator of risk development of vascular disease.[11] A clear correlation was found between the serum level of Lp(a) and its accumulation in the vessel wall.[12] Recently much interest has been focused on Lp(a) as an important marker of CHD.The level of Lp (a) is genetically determined, and when elevated, cannot be lowered by alterations in food intake or by most of the cholesterol lowering agents. Diabetic patients are reported to have higher Lp(a) values than nondiabetic persons and levels are still more significantly elevated in patients with diabetic complications.[13] The data on relationship between Lp(a) and diabetes is scarce and the data on Lp(a) in Asian Indian diabetics is still meagre.[14] Therefore the present study has been undertaken to assess the serum concentration of Lp(a) in patients with diabetes mellitus and to study any association of HbA1C with lipid profile and Lp(a) levels.

METHODOLOGY

This case control study was conducted at Adichunchanagiri Institute of Medical Sciences, Karnataka, India. A total number of 80 subjects participated in the present study. Forty controls and 40 clinically diagnosed cases of diabetes mellitus patients attending out- patient and inpatient departments of ShriAdichunchanagiri Hospital and Research Center (SAH&RC) were included in the study. Age and sex matched healthy individuals are taken as control group. The study was approved by ethical and research committee of SAH&RC. Patients with signs and symptoms of obstructive jaundice, hypothyroidism, hypopituitarism, epileptic patients, psychiatric disorders & nephrotic syndrome were excluded from study. Non-probability convenient sampling method was adopted for sample selection. After obtaining informed consent from patients and controls the data was collected using semi structured questionnaire. The questionnaire included the following information like, socio demographic data, detailed medical historyand relevant clinical examination data.

Collection of blood sample

Under aseptic precautions,7ml of Blood sample in fasting state was drawn from controls and clinically diagnosed cases of DM.Then the blood sample was divided into 3 test tubes, marked as 1, 2 and 3 and analyzed respectively for blood glucose (FBS & PPBS), Lp(a) & other lipid parameters (TAG, Chol, HDL, VLDL & LDL) and HbA1c. 1. Test tube 1 containing 2ml of blood with anticoagulant was used for estimation of blood glucose by Glucose Oxidase method. [15] 2. Test tube 2 containing 3ml of blood with no anticoagulant was allowed to clot and serum was separated. Serum was used for measurement ofTAG by GPO-Trindermethod[15,16], Cholesterol by CHOD-POD method[17], HDL by Phosphotungstic acid method[18], VLDL was calculated by formula (TG/5)[8], LDL was derived by FredricksonFriedwald formula [(TC-HDL) – TG / 5] [8] & [Lp(a)] was estimated by Immunoturbidometric method.[19] 3. Test tube 3 containing 2ml of whole blood was used for estimation of HbA1c by Affinity Chromatography. [20, 21] The chemicals and reagents used for the procedures were of analytical grade. Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented as Mean ? SD and results on categorical measurements are presented in Number (%). Significance is assessed at 5 % level of significance.Statistical significance between two groups (Inter group analysis) was studied using Student t-test (two tailed, independent). Chi-square/Fisher Exact test has been used to find the significance of study parameters on categorical scale between two groups.

RESULTS

The results of the study parameters FBS, PPBS, HbA1c, TAG, Chol, HDL, LDL, VLDL, Lp (a), are depicted in tabular form.  Table 1 shows the demographic distribution between control group and patient group. Samples are age and gender matched with P=0.113. Table 2 gives the results of FBS, PPBS & HbA1c levels of patients and control group presented as Mean±SD. There is increase in all 3 parameters in patients compared to controls which is statistically strongly significant (p<0.001). Table 3 gives the results of lipid profile and Lp (a) levels of patients and control group expressed as Mean±SD. There is strongly significant increase in TAG, HDL, VLDL & Lp (a) levels in patients compared to controls, whereas cholesterol & LDL showed no statistical significance. Table 4 gives the results of Association between HDL, LDL, Chol and Lp (a) with HbA1c (HbA1c / HDL, HbA1c / LDL, HbA1c / Chol & HbA1c / Lp (a)) & Chol / HDL levels of patients and control group. HbA1c / HDL, HbA1c / LDL & HbA1c / Chol ratios shows statistically strongly significant results in patients when compared to controls, whereas HbA1c/Lp(a) ratio shows no significance.

DISCUSSION

The present study shows FBS & PPBS values of patients higher than upper limit which correlated well with the clinical diagnosis. HbA1c is done to monitor the control of blood glucose in DM. Several studies have shown the positive correlation of HbA1c with duration of DM and as a strong predictor of risk (cardiovascular diseases) for diabetes complications. [22] HDL, LDL, TAG and Chol are well known risk factors for complications of DM like CHD. In a study by H. Surekha Rani Et.al., it is observed that FBS and PPBS, Chol, VLDL, LDLs, TAGs were high and the levels of HDLs were low compared to controls. [5] In diabetic dyslipidemia, high TAG tend to coexist with low HDL and small, dense, undesirable (more atherogenic) type of LDL in their blood (even though their LDL level may be normal). In the present study we found significantly increased levels of TAG and VLDL and decreased HDL levels. But no significant change was observed with serum levels of LDL and total cholesterol. Studies have shown that high Lp(a) in blood is a risk factor for CHD, cerebrovascular disease(CVD), atherosclerosis,thrombosis, and stroke.[23] Present study also shows statistically significant increase (p<0.001) in the levels of Lp(a) in cases compared to the controls predicting the possibilities of CHD in diabetic complications. The mean values of Chol/HDL ratio are significantly higher in diabetics than nondiabetics. Increased Chol/HDL ratio increases the risk of coronary artery disease. Study by Elizabeth et.al, observed that LDL and HDL cholesterol were significantly associated with HbA1c. HDL cholesterol was inversely associated with HbA1c where as LDL cholesterol was positively associated with HbA1c in diagnosed diabetics. [24] In present study there is no significant change in the LDL and total cholesterol levels between cases and controls. However there is a significant difference in the HbA1c/LDL & HbA1c/Chol ratios between cases and controls. Similarly we also observed a significant difference in HbA1c/HDL ratio (p<0.001) indicating the inverse relation between HDL and the HbA1c levels. An important risk factor evaluated in the study, Lp (a), showed a significant rise in the serum levels in DM patients compared to controls but its levels were not significantly associated with HbA1c levels which is a standard risk factor for the CHD.

CONCLUSION Lp (a) may not be an independent risk factor for CHD in patients with DM and Chol/HDL, HbA1c/LDL & HbA1c/Chol may be better indicators in determining the risk factors of CHD in DM than evaluating the parameters individually. However further studies with large sample size are required to evaluate the correlation between the Lp (a) and other lipoprotein factors with HbA1c to assess the risk for development of CHD in DM.

ACKNOWLEDGEMENT

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

References:

REFERENCES

1. Fauci AS, Kasper DL, Braunwald E, Hauser SL, Longo DL, Jameson JL Et al. Harrison’s Principles of Internal Medicine. 17th Ed. United States of America: McGraw-Hill Medical publishing division; 2008. Chapter 338,Diabetes Mellitus: p. 2275-304.

2. Hilary King, Ronald Aubert E, William Herman H. Global Burden of Diabetes, 1995- 2025: Prevalence, numerical estimates, and projections.Diabetes Care 1998;21:1414–31.

3. Ramachandran A, Snehelatha C, Latha E, Vijay V, Viswanathan M. Rising prevalence of NIDDM in an urban population in India. Diabetologia 1997;40:232–37.

4. Lt Gen SR Mehta, VSM, Col AS Kashyap, Lt Col S Das. Diabetes Mellitus in India: The Modern Scourge. MJAFI 2009;65:50-4.

5. Surekha Rani. H, Madhavi G, RamachandraRao V,Sahay B.K, Jyothy A. Risk Factors for Coronary Heart Disease in Type II DM. Indian Journal of Clinical Biochemistry 2005;20(2):75-80.

6. Zachary T,Bloomgarden. Cardiovascular Disease, Neuropathy and Retinopathy.Diabetes care 2009;32: e64- e 68.

7. Chambless LE, Heiss G, Folsom AR, Rosamond W,Szklo M, Sharrett AR, Clegg LX. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987– 1993. Am J Epidemiol 1997;146:483–94.

8. Burtis Carl A, Ashwood Edward R, Bruns David E.Tietz Textbook of clinical chemistry and molecular diagnostics. 4th Ed. New dehli: Elsevier publishers; 2008. Chapter 26,Lipids, lipopropteins, apolipoproteins and other cardiovascular risk factors: p. 903-83.

9. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 2000;23(Suppl 1):S32–42.

10. Berg K. A new serum in man. The Lp system. ActaPatholMicrobiolScand 1963; 59:369-82.

11. Fijino A, Watanabe T. Kunii H, Yamaguchi N, Yoshinara K, Watanabe Y et al. Lipoprotein(a) is a potential coronary risk factor. JpnCirc J 2000;64(1):51-6.

12. Rath M, Ncendorf A, Reblin T, Dietel M, Knebber HJ. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Atherosclerosis 1989; 9:579-92.

13. KhareKC, Raman PG, Bhatnagar AD, ReemaBhavsar. Serum Lp(a) levels in patients of diabetes mellitus. Int. J. Diab. Dev. Countries 2000;20:79 – 83.

14. Clodi M, Oberbauer R, Bodlay G, Hoffman J, Maurer G, Kostner K. Urinary excretion of apolipoprotein (a) fragments in type I diabetes mellitus patients. Metabolism 1999; 48(3):369-72.

15. Trinder P. Determination of Glucose in Blood Using Glucose Oxidase with an. Alternative Oxygen Acceptor. Ann. Clin. Biochem 1969;6:24.

16. Product data sheet, triglyceride-G code no.997-69801,WAKO Pure Chemical Industries Ltd., Dallas,TX.

17. Allain CC, Poon LS, Chan CS, Richmond W. and Fu P., Clin.Chem 1974;20(4):470-5.

18. Burstein M, Scholnic H.R., Morfin RJ.Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 1970;11(6):583-95.

19. Poulik, MD, Weiss ML. in F.W. Putman, Editor,"The Plasma Proteins", second Edition, Academic Press, New York, vol2;52-108.

20. Trivelli, LA, Ranney PH, Lai HT. Haemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;284:355–8.

21. Gonen B, Rubenstein AH. Determination of glycohemoglobin.Diabetologia. 1978;15:1–5.

22. Robert McCarter J, James Hempe M, Ricardo Gomez, Stuart Chalew A. Biological Variation in HbA1c Predicts Risk of Retinopathy and Nephropathy in Type 1 Diabetes. Diabetes Care 2004;27:1259–64.

23. Christian Wilde (2003). Hidden Causes of Heart Attack and Stroke: Inflammation,Cardiology's New Frontier.Abigon Press. pp. 182–183. ISBN 0- 9724959-0-8.

24. Elizabeth Selvin, Josef Coresh, Sherita Golden H, Lori L. Boland,Frederick Brancati L, Michael Steffes W. Glycemic Control, Atherosclerosis, and Risk Factors for Cardiovascular Disease in Individuals with Diabetes. Diabetes Care. 2005;28(8):1965–73.

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One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

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This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

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‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


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A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
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A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
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A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
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A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
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A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.



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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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