International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - Vol 10 Issue 06, March, 2018

Pages: 07-09

Date of Publication: 28-Mar-2018


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Significance of Secreted Frizzled Related Protein 4 (SFRP4) in Type 2 Diabetic and non Diabetic Subjects in the Rural Agricultural Population Who are Exposed to Pesticides for the Prediction of Diabetes Mellitus

Author: Velayutharaj A., Muthumani L., Senthilnathan R., Rajendran S.M., Shivakumar R., Saraswathi R.

Category: Healthcare

Abstract:Introduction: Diabetes mellitus and its complications have become a major health problem for the public of South East Asians especially in India. Exposure to organophosphorus pesticides which are very much in use for the agriculture purpose worldwide produces disorders of glucose homeostasis, because there is increasing evidence of environmental pollutants especially pesticides to the development of insulin resistance and type2 diabetes mellitus. Background: To study the significance of Secreted Frizzled Related Protein4 (SFRP4) levels in both diabetic and non diabetic rural agriculture population who are exposed to pesticides for the prediction of diabetes mellitus. Total 46 Type 2 Diabetic patients and 42 non diabetic subjects were included in this study.
Results: The Pearson correlation coefficient was used to find the correlation between SFRP4 and Glycated hemoglobin (HbA1c) and Fasting glucose. And the correlation was found between SFRP4 levels with HbA1c (R=0.65) and also found between SFRP4 and fasting glucose levels (R=0.54) and both are statistically significant (p-< 0.05).
Conclusion: If properly intervene the population with proper health education regarding precautionary measures for the use of pesticides and awareness of diabetes who have a strong family history of diabetes mellitus with upper normal level after testing this new marker SFRP4, we can delay or even may reduce the incidence of diabetes mellitus in the rural population due to the exposure of pesticides.

Keywords: SFRP4-Secreted Frizzled Related Protein, HbA1c-Glycated Hemoglobin, T2DM-Type 2 Diabetes Mellitus, OPCOrgano phosphorous compounds.

DOI: 10.7324/IJCRR.2018.1062

Full Text:

Introduction:

With all precautionary and therapeutic approaches by the Government and Non-governmental organizations diabetes and its complications have become a major health problem for the public of South East Asians especially in India. There are many risk factors have been identified like lifestyle factors, genetic factors and for the prediction of diabetes that have been proposed and tested. Apart from these lifestyles and genetic factors, pesticides like organophosporous compounds (OPCs) which are very much in use for the agriculture purpose worldwide, disorders of glucose homeostasis are one of the most important complications following exposure to organophosphorus pesticides , because there is increasing evidence of environmental pollutants especially pesticides to the development of insulin resistance and   type2 diabetes mellitus1 . Hectors et al. stated that beta cell function has been found to be disrupted by the organophosphate pesticides like malathion and disturbance in carbohydrate metabolism2.  Many previous studies have proved that the use of OPCs like malathion, diazinon, chloripyrifos, dichlorvos without any proper precautionary measures may cause different health problems, including endocrine, reproductive, nervous, and immune systems3, 4, 5.

An adipocytokine known as Secreted frizzled related protein4 (SFRP4) one of the recently discovered group of 5 proteins has been described as a potential bio marker of early pancreatic beta cell dysfunction6. And it was stated in a study that there was a significant inverse correlation of SFRP4 expression in human pancreatic islets with insulin secretion and positive relationship with HbA1C levels was observed7. There was much focus on the risk factors for diabetes has been elaborated on the basis of life styles and genetics. So the aim of the study is to know the relationship between SFRP4 levels and type-2 diabetes mellitus among pesticide users in the rural population.

Aim: To study the significance of SFRP4 levels in both diabetic and non diabetic rural agriculture population who are exposed to pesticides for the prediction of diabetes mellitus.

Objectives:   
1.To know the levels of SFRP4 in Diabetes and non-diabetes persons.  
2. To reveal the role of pesticides in relation to the SFRP4 levels in Diabetes and non-diabetes persons.

 Materials and Methods:

  • 46 Type2 Diabetic (T2DM) and 42 non diabetic Male and Female subjects with age ranges from 20 to 75 were included in this study.

  •  Inclusion criteria: The study subjects who were exposed to pesticides for more than one year living in the rural area near by the Tertiary Care Teaching Hospital

  •  Exclusion criteria: Type-1Diabetes Mellitus(DM), Secondary causes of DM, Gestational DM and Diabetic patients with its complications were excluded from this study

  • After got the informed written consent from all patients and subjects, 5 ml of fasting blood sample was collected, 3ml in a clot activator tube for the analysis of Fasting plasma glucose in BS 420 auto analyzer, serum quantitative analysis of SFRP4 by ELISA method in the Biorad-680 system and 2 ml of blood into the EDTA tube for the analysis of HbA1c% by NGSP/IFCC approved method.

Results: The results were analyzed in SPSS16.0 version. The Mean value of SFRP4 among diabetic study subject was 3.2 + 0.6 (Normal value considered was <3) and for the non diabetic people 2.3 0.5 and the difference is statistically significant (p-<0.05) The Pearson correlation coefficient was used to find the correlation between SFRP4 and HbA1c and Fasting glucose. And the correlation was found between SFRP4 levels with HbA1c (R=0.65) and also found between SFRP4 and fasting glucose levels (R=0.54) and both are statistically significant (p-<0.05).

Table1.  Comparison of the values of Secreted Frizzled Related Protein4 (SFRP4) in Diabetic and Non diabetic study groups

Discussion: Since T2DM is a progressive disease which does not cause specific symptoms for many years, diagnosis at an early stage is of outmost importance and to reduce the burden for our health system in general. In spite of many biomarkers available to confirm the disease, the recent trend is to control the disease by the target base inhibiting of enzymes or proteins. The Malekirad etal study had confirmed that farmers are prone to neuropsychological disorders and diabetes caused by organophosphorous compounds (OPC) exposure8. Suarez-Lopez JR, Lee DH, Porta M, et al. stated those after decades of exposure to PCBs and OCPs at background environmental levels, glucose homeostasis may worsen irrespective of their BMI after 5thdecade of life9. Hansen et al.found that there was an increase in the prevalence of prediabetes among the Bolivian pesticide sprayers compared with a control group10

Michael et al in their prospective study showed that higher SFRP4 concentrations are associated with T2DM and the metabolic syndrome and SFRP4 concentrations are a novel marker of impaired glucose and triglyceride metabolism which is consistent with our study11. Elevated systemic SFRP4 causes reduced glucose tolerance through decreased islet expression of Ca2+ channels and suppressed insulin exocytosis thus SFRP4 provides a link between islet inflammation and impaired insulin secretion12.

Mahdi and his colleagues pointed out that increased SFRP4 causes reduced glucose tolerance through decreased islet expression of Ca++channels and suppressed insulin exocytosis thus provides a link between islet inflammation and impaired insulin secretion. Further, they have suggested that SFRP4 could be a potential biomarker for islet dysfunction in T2DM. The elevation of SFRP4 in serum several years before the diagnosis highlights this protein as a potential biomarker for the low-grade islet inflammation that is commonly seen in T2D, and it might prove useful for early disease detection in combination with glucose and other biomarkers and their data also raised the exciting possibility that SFRP4 could be a therapeutic target for specific treatment of islet dysfunction13. Also in a study by the Shazia Anwer Bukhari found that there is a possible treatment of type 2 diabetes mellitus by inhibiting the protein SFRP4 using the compounds like cyclothiazide, clopamide and perindopril14. Brix JM etal demonstrated that increased levels of SFRP4 found in patients with different types of diabetes, suggesting that SFRP4 irrespective of type of diabetes is generally involved in islet dysfunction and potentially due to subclinical inflammation15. In our study also the findings showed that there is a statistically significant association between SFRP4 levels and Type-2 Diabetes mellitus.

Conclusion:

Since diabetes now considered as one of the global economical burden because of its complications, it is mandatory to find out newer markers and therapeutic approach. Many previous studies had been pointed out that SFRP4 is a potential marker of beta cell dysfunction. So if properly intervene the population with proper education regarding precautionary measures for the use of pesticides and awareness of diabetes who have a strong family history of diabetes mellitus with upper normal level after testing this new marker SFRP4, we can delay or even may reduce the incidence of diabetes mellitus in the rural population due to the exposure of insecticides. Further large scale population study is needed for the importance of SFRP4 estimation in T2DM in farmers who are in the exposure of OPCs for the newer therapeutic implications.

Conflict of Interest: Authors have no conflict of interest

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:

  1. Swaminathan K . Pesticides and human diabetes: a link worth exploring? 2013. Diabet Med.30(11):1268-71

  2. Hectors TL1, Vanparys C, van der Ven K, Martens GA, Jorens PG, Van Gaal LF, Covaci A, De Coen W, Blust R. Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function. Diabetologia. 2011 Jun;54(6):1273-90. Epub 2011 Mar 27.  [PubMed ]

  3. Soltaninejad K, Abdollahi M. Current opinion on the science of organophosphate pesticides and toxic stress: A systematic review. Med Sci Monit 2009;15:75-90.

  4. Mostafalou S, Abdollahi M. Current concerns on genotoxicity of pesticides. Int J Pharmacol 2012;8:473-4.

  1. Mostafalou S, Abdollahi M. Concerns of environmental persistence of pesticides and human chronic diseases. Clin Exp Pharmacol 2012;S5:e002.

  1. K. Bergmann, G. Sypniewska Secreted frizzled-related protein 4 (SFRP4) and fractalkine (CX3CL1) - Potential new biomarkers for β-cell dysfunction and diabetes. Clinical Biochemistry 47 (2014) 529–532                                                                                       

  2. Grazyna Sypniewska . How to diagnose diabetes? Biochemia medica 2014:24(Suppl 1) S3134

  3. Malekirad AA et al. NEUROCOGNITIVE, MENTAL, AND GLUCOSE DISORDERS IN OP-EXPOSED FARMERS Arh Hig Rada Toksikol 2013;64:

  4. Suarez-Lopez JR, Lee DH, Porta M, Steffes MW, Jacobs DR Jr

  1. .Persistent organic pollutants in young adults and changes in glucose related metabolism over a 23-year follow-up .2015. Environ Res. 137:485-94        

  2. Hansen MR, Jørs E, Lander F, Condarco G, Schlünssen V.Is cumulated pyrethroid exposure associated with prediabetes"? A cross-sectional study. J Agromedicine. 2014;19(4):417-26.

  1. Michael M Hoffmann, Christian Werner, Michael Böhm, Ulrich Laufs and Karl Winkler. Association of secreted frizzled-related protein 4 (SFRP4) with type 2 diabetes in patients with stable coronary artery disease. Cardiovasc Diabetol. 2014; 13: 155.

  1. Wilson C. Diabetes: SFRP4—a biomarker for islet dysfunction? Nature Reviews Endocrinology 2013: 9‚ 65.

  1. Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, Axelsson AS, Zhou Y, Jing X, Almgren P, Krus U, Taneera J, Blom AM, Lyssenko V,Esguerra JL, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH. Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes. Cell Metab. 2012 Nov 7;16(5):625-33.

  1. Shazia Anwer Bukhari , Waseem Akhtar Shamshari , Mahmood-Ur-Rahman  , Muhammad Zia-Ul-Haq, and Hawa Z. E. Jaafar. Computer Aided Screening of Secreted Frizzled-Related Protein 4 (SFRP4): A Potential Control for Diabetes Mellitus. Molecules 2014, 19, 10129-10136; 

  1. Brix JM, Krzizek EC, Hoebaus C, Ludvik B, Schernthaner G, Schernthaner GH Secreted Frizzled-Related Protein 4 (SFRP4) is Elevated in Patients with Diabetes Mellitus. Horm Metab Res. 2016 May;48(5):345-8.

Research Incentive Schemes

Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

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.

Women Researcher Award:

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Best Article Award

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 COLAKOGLU 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 Arpita M. et al 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
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List of Awardees

Awardees of COVID-19 Research

Woman Researcher Award

A Study by Neha Garg et al. entitled "Optimization of the Response to nCOVID-19 Pandemic in Pregnant Women – An Urgent Appeal in Indian Scenario" published in Vol 12 issue 09

A Study by Sana Parveen and Shraddha Jain entitled "Pathophysiologic Enigma of COVID-19 Pandemic with Clinical Correlates" published in Vol 12 issue 13

A Study by Rashmi Jain et al. entitled "Current Consensus Review Article on Drugs and Biologics against nCOVID-19 – A Systematic Review" published in Vol 12 issue 09

Emerging Researcher Award

A Study by Madhan Jeyaraman et al. entitled "Vitamin-D: An Immune Shield Against nCOVID-19" published in Vol 12 issue 09

Study by Dheeraj Kumar Chopra et al. entitled "Lipid-Based Solid Dispersions of Azilsartan Medoxomil with Improved Oral Bioavailability: In Vitro and In Vivo Evaluation" published in Vol 12 issue 19


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