International Journal of Current Research and Review
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IJCRR - 7(4), February, 2015

Pages: 54-59

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PROTEIN ENERGY WASTING (PEW) / CACHEXIA IN CHRONIC KIDNEY DISEASE - ROLE OF LEPTIN AND INSULIN

Author: D. Ponnudhali, P. Nagarajan, R. Shankar

Category: Healthcare

Abstract:Background: The prevalence of protein energy wasting (PEW)/ cachexia is very high among patients with chronic kidney disease (PEW), increasing in severity with the progression of the disease. Among other factors, increased serum Leptin levels and insulin resistance have been implicated in the pathogenesis of PEW/cachexia in CKD Aim and objectives: To assess the serum leptin & insulin levels along with HOMA IR (Homeostasis model assessment-Insulin Resistance) in non diabetic chronic kidney disease patients and to study the correlation of these parameters with glomerular filtration rate (GFR) & body mass index (BMI). Materials and methods: Non-diabetic CKD patients (group1; n=45) and healthy non-diabetic individuals (group 2; n=45) with normal renal function were recruited for the study. Serum leptin and Insulin levels were assessed using ELISA kits. Calculated values of HOMA IR & BMI were taken for the analyses.Statistical analysis: The statistical analysis was done using SPSS version 16. The parameters were compared among the 2 groups using Independent t test and correlation coefficient. Results: Serum Leptin levels (24.15 \? 17.44 ng/ml) were increased significantly (p=.000) in group 1 patients compared to those in group 2 (7.50 \? 1.28 ng/ml). Serum insulin levels (p=.000) were increased in CKD patients (15.49 \? 9.39 \?U/ml) from that of the healthy controls (7.50 \? 1.28\?U/ml). The HOMA IR was also significantly high (p=0.000) in the CKD group ( 3.69 \? 2.26) than the controls (1.69 \? 0.35). Leptin, insulin & HOMA IR showed a highly significant negative correlation with GFR & BMI .The serum albumin and total cholesterol in the CKD group were 3.20 \? 0.19 g/dl & 127.47 \? 31.75 mg/dl respectively. Conclusion: Hyperleptinemia and insulin resistance may be responsible for protein energy wasting/cachexia associated with CKD.

Keywords: Leptin, protein energy wasting (PEW), Cachexia, Insulin resistance

Full Text:

INTRODUCTION

Protein energy wasting (PEW)/ cachexia is highly prevalent among patients with chronic kidney disease(CKD). PEW is a devastating complication of CKD, as it increases the incidence of cardiovascular outcomes as well as the morbidity & mortality associated with CKD, making it a major clinical problem. The International Society of Renal Nutrition and Metabolism (ISRNM) panel has described PEW as a state of decreased body stores of protein and energy fuels (body protein and fat masses). It describes a progressive loss of adipose tissue and lean body mass, with cachexia constituting the severe form of protein energy wasting (PEW) [1].The PEW/cachexia syndrome in CKD patients consists of anorexia, increased energy expenditure, decreased protein stores characterized by low serum albumin, loss of body weight and loss of muscle mass. The etiology of PEW in chronic kidney disease (CKD) is complex and includes inflammation, metabolic acidosis, insulin resistance, increase in serum leptin [2], transient catabolic illnesses, hyperparathyroidism and so many other conditions. CKD is associated with insulin resistance even from an early stage, when the GFR is normal [3]. Leptin is an adipocyte- derived hormone that has an inhibitory effect on food intake while it increases the energy expenditure. Elevated levels of serum leptin have been reported in CKD patients and has been linked with the pathogenesis of PEW/cachexia [4,5]. Hence we decided to assess the serum leptin & insulin levels along with HOMA- insulin resistance, in non diabetic CKD patients, graded to have PEW/ cachexia. We have also correlated the levels of these parameters with glomerular filtration rate(GFR) and body mass index(BMI). This study is an attempt to highlight the role played by leptin and insulin in the pathogenesis of PEW in non diabetic CKD and, its relation to the declining GFR & BMI.

MATERIALS AND METHODS

Our study has been conducted in patients with chronic kidney disease who were non diabetic and not on dialysis, recruited from the department of Nephrology, Government Mohan Kumaramangalam Medical College Hospital, Salem. Friends, family members and colleagues of the patients constituted the control group. Written consent was obtained from all the subjects, after clearly explaining to them about our study protocol. This study was approved by the ethical committee of Govt Mohan Kumaramangalam Medical College Hospital. Group 1 comprised of 45 non diabetic patients with Chronic Kidney Disease (CKD), diagnosed and staged, based on NKF K/DOQI guidelines [6]. Group 2 comprising of 45 healthy adults with normal renal function (GFR > 90 ml/min), formed the control group. The study group 1 included CKD patients, not on hemodialysis/ peritoneal dialysis. Patients with history of diabetes, metabolic syndrome, endocrine disorders, obesity, pregnancy, malignancy or any other terminal illness were excluded from the study. The control group 2 included healthy individuals, with normal renal function. Subjects with diabetes, hypertension, renal disease, chronic infections, pregnancy, systemic illness, endocrine disorders, malignancy or neuropsychiatric illness were excluded from the study. All subjects in both the control and study group were age and sex matched.

Laboratory analysis:

After an overnight fast of at least 8 hrs, fasting blood samples were collected from both the patients and controls. Plasma and serum were separated immediately after collection, and stored at -20°C , until further analysis. Complete blood count, urine routine , blood glucose, urea, creatinine, albumin & Total Cholesterol were estimated using the semi autoanalyzer- Microlab 300. These biochemical analyses were done, in the clinical Biochemistry Laboratory, VMKV Medical College, Salem. Serum Leptin was analyzed using DRG (sandwich) EIA 2395 ELISA kit [7]. Serum Insulin was analyzed using Monobind’s Insulin/ MAPS ELISA kit [8]. Homeostasis model assessment-Insulin Resistance (HOMA-IR) was calculated using the formula, HOMA-IR = fasting serum insulin (µIU/ml)* fasting plasma glucose (mg/ dl)/405 [9]. GFR was calculated using the MDRD (Modification of Diet in Renal Disease) formula available online [10].

PROTEIN ENERGY WASTING (PEW)/ CACHEXIA:

We have tried to assess the protein energy wasting (PEW) in the CKD patients based on the following criteria, proposed by The International Society of Renal Nutrition and Metabolism (ISRNM):

We have also calculated BMI using the formula: Weight in kilograms / (height in meters)2 Kg/m2 [12].The standard weight status categories associated with BMI ranges for adults are Herewith we have selected 4 parameters to diagnose the protein energy wasting (PEW) in CKD patients - serum albumin, serum cholesterol, BMI & Dietary Energy Intake- DEI. Nutritional diaries were provided to the CKD patients and they were taught to make entries, which will explain their complete dietary regimen through out the day. From the entries their dietary energy intake was calculated, for further analysis.

Statistical analysis

Statistical analysis was done using the software SPSS version 16. Data was expressed as mean ± 2SD and differences in mean between the 2 groups were analyzed using independent t test. Bivariate correlations of Leptin, Insulin & insulin resistance (IR) with BMI and GFR, were performed using Pearson’s correlation.

RESULTS

The present study was conducted in 45 non diabetic CKD patients (group1) not on dialysis and 45 healthy controls (group2), with normal renal function. Serum leptin, insulin, albumin and total cholesterol were analyzed in the blood samples. HOMA IR and BMI were the calculated parameters, taken for the study. The results are displayed in Table 1. Serum Leptin levels (24.15 ± 17.44 ng/ml) were increased significantly (p=.000) in group 1 patients compared to those in group 2 (7.50 ± 1.28 ng/ml). Serum insulin levels (p=.000) were increased in CKD patients (15.49 ± 9.39 µU/ml) compared to the healthy controls (7.50 ± 1.28µU/ml). The HOMA IR was also significantly high (p=0.000), in the CKD group. The correlations of serum Leptin, Insulin & HOMA-IR with BMI & GFR, were performed using Pearson’s correlation which is depicted in Table-2. Leptin, Insulin & HOMA IR were found to have a highly significant negative correlation with GFR & BMI . Indicators of protein energy wasting/ cachexia: Certain biochemical tests were done to assess the status of protein energy wasting/ cachexia. Serum albumin (3.20 ± 0.19g/dl) was found to be significantly decreased (p=.000) in the group 1 patients from that of the group2 (4.1 ± 0.30 mg/dl) subjects. Serum cholesterol levels (group1: 127.47 ± 31.75mg/dl, group2: 161.16 ± 39 mg/dl) showed a significant decrease in group1 patients (p=.000). The BMI levels were significantly decreased (p=.001) in the group1 (21.96 ± 3.46 kg/m2) patients compared to those in group 2 (25.50 ± 4.61 kg/m2). We have found that the serum albumin levels were below 3.8 g/dl in the CKD patients. The serum cholesterol levels though were decreased in CKD patients , their levels were not below 100mg/dl. The BMI levels were below 23 in the CKD patients. All these values are shown in Table 1. The dietary energy intake (DEI) of CKD patients was assessed from their nutritional dairies. Their mean DEI was found to be less than 24 kcal kg−1day−1 . The CKD patients in group 1 satisfy three of the four criteria stated by the ISRNM [11]. Hence the patients in group 1, can be placed under the category of protein energy wasting (PEW)/ cachexia syndrome.

DISCUSSION

We have conducted our study in 45 non diabetic predialysis CKD patients and 45 healthy controls. Serum leptin levels have been significantly increased in CKD patients (group1) compared to healthy controls (group 2). There is negative significant correlation of serum leptin levels with BMI & GFR. Leptin is a 167 amino acid peptide , an adipocytokine, produced abundantly by the adipose tissue and acts as a major regulator of food intake and energy homeostasis. It circulates as both free and protein- bound form and exerts inhibitory effects on food intake while increasing energy expenditure [13]. The leptin receptor belongs to class I cytokine receptor superfamily and possesses strong homology to the signal transducing subunits of the IL-6 receptors [14]. At least five isoforms of receptors (OBRa, OBRb, OBRc, OBRd, and OBRe) are known to exist and result from alternate gene splicing. Among these most biological effects of leptin are mediated by the leptin receptor OBRb, which is primarily present in the hypothalamus, where action of leptin is important in energy homeostasis. The OBRb receptors are also expressed in peripheral tissues including heart, skeletal muscle , adrenals, kidneys, adipocytes , smooth muscle cells, endothelial cells etc . An association of increased serum leptin levels with CKD, have been emphasized in certain studies, in different populations. [15,16,17]. Leptin is cleared from the circulation by kidney, by glomerular filtration followed by metabolic degradation in the renal tubules [17]. In CKD, due to reduced GFR, there is increased serum leptin levels. We have also found a negative significant correlation between serum leptin levels and GFR , which confirms that serum leptin is increased due to declining renal function in CKD. In CKD, inflammation is another important factor which contributes to hyperleptinemia [13]. The increased leptin levels may mediate protein energy wasting and cachexia, by regulating food intake and energy consumption via signalling through the hypothalamic melanocortin system [18]. Pro-opiomelanocortin (POMC) is a propeptide precursor that is produced in neurons found in the hypothalamic arcuate nucleus [19]. POMC neurons are thought to provide tonic inhibition of food intake and energy expenditure by production and release of α-melanocyte stimulating hormone (α- MSH) [4]. α- MSH in turn activates the hypothalamic type 4 melanocortin receptor (MC-4R), leading to suppressed food intake and increased energy expenditure. Leptin is able to activate the POMC neurons in the hypothalamus, triggering the production and release of α- MSH, which binds to MC3/MC4 receptors expressed on the hypothalamic nuclei, inducing a reduction of appetite and increase in energy consumption [20]. Leptin also suppresses the activity of Neuropeptide Y & Agoutirelated peptide (AGRP), which are endogenous antagonists of MC- 4R [21]. Hence increased serum leptin levels could be an important causal factor for protein energy wasting/ cachexia seen in CKD patients [4,5].This fact has been tested by Wai Cheung et al, who have identified that leptin causes MC-4R blockade and that it plays a significant role in transducing cachexic signals in CKD [4]. Pecoits- Filho et al suggest that free circulating leptin concentrations are elevated in patients with end stage renal disease and may be associated with inflammation associated cachexia [5]. As we have observed in our study, serum leptin increases as the BMI decreases, showing a probable relation between increasing leptin levels and PEW/ cachexic manifestations. Hence leptin may play an important role in anorexia/ cachexia syndrome seen in CKD patients. Some of the causes of protein energy wasting (PEW) in CKD patents are inflammation, metabolic acidosis and insulin resistance [21]. Leptin secretion have been found to be regulated by insulin, glucocorticoids and catecholamines [22]. In our study we have identified the occurrence of hyperinsulinemia and increased HOMA-IR, in CKD patients. Hyperinsulinemia may be due to reduced clearance of insulin by the kidneys / compensatory to insulin resistance. We have also obtained negative significant correlation between serum insulin levels & HOMA-IR with GFR and BMI. The insulin resistance in CKD, results in uremic myopathy due to increased muscle breakdown. Insulin has an anticatabolic effect, by activating protein synthesis and inhibiting proteolysis. In insulin resistance, there is decreased utilization of glucose as an energy source, by the skeletal muscles.CKD attenuated insulin stimulated protein synthesis and increased protein degradation in skeletal muscle [23]. Many studies have documented insulin resistance as an important complication of CKD, with varied metabolic changes [24,25,26]. In CKD, insulin resistance is due to a post-receptor signalling defect : reduced activity of PI3K (phoshpatidylinositol 3-kinase) in turn causing reduced levels of phoshorylated Akt (pAkt). This dysfunction of PI3K signalling pathway is a common initiator of muscle protein degradation by enhancing the activity of ubiquitin-proteosome pathway, in muscle [27]. Ubiquitin proteosome proteolytic (Ub-P’some) system consists of the 7- KDa protein ubiquitin, E3 ubiquitin ligases (atrogin-1, MAFbx & MuRF1) and proteosome (large multi-subunit complex found in all mammalian cells). Insulin resistance activates the Ub-P’some system through suppressing PI3 Kinase pathway & by activating MEK/ERK pathway [28]. This PI3K signalling defect activates FOXO group of transcription factors ,which in turn induces the expression of ubiquitin conjugating enzymes atrogin-1, MAFbx & MuRF1 [29]. Insulin resistance also results in the activation of MEK/ERK pathway, causing increased expression of ubiquitin (UbC) . Hence the Ubiquitin proteosome proteolytic (Ub-P’some) system is activated as shown in figure1. The suppression of PI3K signalling pathway also results in activation of Bax proteins which in turn activates the enzyme caspase 3. Caspase 3 plays an initial role in muscle protein degradation, by cleaving actomyosin and presenting them to the ATP dependent Ubiquitin proteosome proteolytic (Ub-P’some) system which in turn degrades the monomeric actin/myosin fragments but not the actomyosin complexes [30]. Hence increased insulin resistance seen in CKD patients may play an important role in muscle protein degradation causing a reduction in lean body mass. An important consequence of insulin resistance in CKD is the pathogenesis of PEW/ cachexia [31]. Leptin and insulin- Role in kidney damage: Serum leptin levels and insulin resistance increases in chronic kidney disease and both these parameters play an important role in the pathogenesis of PEW/ cachexia. Apart from this both leptin & insulin are known to activate the sympathetic nervous system, causes impairment of natriuresis

and inhibition of nitric oxide synthesis [32,33]. All these factors may contribute to the up regulation of blood pressure and hence worsening of renal function.

CONCLUSION

The present study shows an increase in serum leptin, insulin and HOMA-insulin resistance, showing a strong correlation with GFR & BMI. Increased leptin signalling and insulin resistance might significantly contribute to the development of protein energy wasting (PEW)/ cachexia syndrome in patients with chronic kidney disease. Understanding the role played by these parameters might help in early intervention of the wasting disorder, when the skeletal muscle complications might still be reversible. The emerging role of therapeutic agents like AGRP (agouti-related peptide- endogenous antagonist of MC-4R receptors) & orexigenic agents/appetite stimulants (neuropeptide Y, Ghrelin) and their appropriate use in maintaining the skeletal muscle homeostasis, should be further confirmed by well controlled studies.

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

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A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
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
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
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
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
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
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
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
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
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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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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