Advertisement

A low GLP-1 response among patients treated for acute organophosphate and carbamate poisoning: a comparative cross-sectional study from an agrarian region of Sri Lanka

  • Devarajan Rathish
  • Indika Senavirathna
  • Channa Jayasumana
  • Suneth Agampodi
  • Sisira Siribaddana
Research Article
  • 25 Downloads

Abstract

Higher incidence of diabetes along with increased use of pesticides is seen in Southeast Asia. Recent hypothesis postulated a link between acetylcholinesterase inhibitor insecticides and type 2 diabetes through the GLP-1 pathway. This study compares the GLP-1 response between groups with low and high red blood cell acetylcholinesterase (RBC-AChE) activity. A comparative cross-sectional study was conducted amongst patients who were within 3 months after an acute organophosphate or carbamate poisoning (acute group) and amongst vegetable farmers with low (chronic group) and high (control group) RBC-AChE activity. Acute (366 mU/μM Hb) and chronic (361 mU/μM Hb) groups had significantly lower RBC-AChE activity in comparison to the control (471 mU/μM Hb) group (P < 0.0001). Only the acute group, which has had atropine therapy, showed a significantly lower 120 min value in comparison to the control group (P = 0.0028). Also, the acute group had significantly low late (P = 0.0287) and total (P = 0.0358) responses of GLP-1 in comparison to the control group. The findings of the study allude towards attenuation of GLP-1 response amongst patients after acute organophosphate and carbamate poisoning. The possibility of an atropine-mediated attenuation of GLP-1 response was discussed.

Keywords

Atropine Organophosphate Carbamate Diabetes mellitus Glucagon-like peptide-1 Incretin effect Acetylcholinesterase activity 

List of abbreviations

ACh

acetylcholine

AChE

acetylcholinesterase

AUC

area under the curve

BMI

body mass index

CKD-EPI

Chronic Kidney Disease Epidemiology Collaboration

eGFR

estimated glomerular filtration rate

ELISA

enzyme-linked immunosorbent assay

GIP

glucose-dependent insulinotropic polypeptide

GLP-1

glucagon-like peptide-1

IQR

interquartile range

NA

not applicable

OGTT

oral glucose tolerance test

OPI

organophosphate insecticide

RBC

red blood cell

T2DM

type 2 diabetes mellitus

tAUC

area under the curve for total response

Notes

Authors’ contributions

DR conceived the idea of the study and all authors participated in designing the study. DR was involved in data collection and analysis. DR and IS were involved in biochemical analysis. All authors were involved in the interpretation of data. DR drafted the manuscript and IS, CJ, SA and SS critically revised it. All authors read and approved the final manuscript.

Funding information

The study was partially funded by the grant awarded by the Research, Publication & Higher Degrees Committee, Rajarata University of Sri Lanka to DR (grant number RJT/RP&HDC/2017/FMAS/R/01) and the sponsorship awarded to DR by the State Pharmaceutical Corporation, Sri Lanka. The above agents did not influence the design of the study, collection, analysis and interpretation of data or the writing of the manuscript.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Ethical clearance was obtained from the Ethics Review Committee of Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka (ERC/2016/80). Institutional permission was obtained from the institutional heads of Teaching Hospital Anuradhapura and Base Hospital Thambuttegama. Informed written consent to participate was obtained from all participants. All necessary measures were taken to preserve participant’s privacy and confidentiality.

Consent for publication

Consent to publish the information provided by the participants was obtained, provided that it will not be possible to identify individual participants in any way.

Supplementary material

11356_2018_3818_MOESM1_ESM.xls (84 kb)
Online Resource 1 (XLS 83 kb)

References

  1. AChE check Control high/low (2018) Securetec Detektions-Systeme AG, Germany. Available at: https://www.securetec.net/sites/default/files/03_Produkte/ChECheck/Dateien/ache_control_acetylcholinesterase_flyer_70531_en_v01.pdf. Accessed 8 February 2018
  2. Adult Tobacco Use Information (2015) National Health Interview Survey. Available at: https://www.cdc.gov/nchs/nhis/tobacco/tobacco_glossary.htm. Accessed 10 March 2017
  3. Ahrén B, Holst JJ (2001) The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes 50(5):1030–1038CrossRefGoogle Scholar
  4. Anini Y, Hansotia T, Brubaker PL (2002) Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 143(6):2420–2426CrossRefGoogle Scholar
  5. Annual Bulletin (2014) Sri Lanka Labour Force Survey, Department of Census and Statistics, Ministry of Finance and Planning. Available at: http://www.statistics.gov.lk/samplesurvey/LFS_Annual%20Bulletin_2014-f.pdf. Accessed 4 February 2018
  6. Balks HJ, Holst JJ, von zur Mühlen A, Brabant G (1997) Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab 82(3):786–790Google Scholar
  7. Census of Population and Housing (2012) Department of Census and Statistics. Ministry of Finance and Planning, Sri LankaGoogle Scholar
  8. Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, H. F. (2009) Diabetes in Asia. Jama 301(20):2129–2140CrossRefGoogle Scholar
  9. Classification and diagnosis of diabetes: standards of medical care in diabetes—2018 (2018) Diabetes Care, 41(Supplement 1), pp. S13–S27Google Scholar
  10. Drinking Levels Defined (2016) National Institute on Alcohol Abuse and Alcoholism. Available at: https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/moderate-binge-drinking. Accessed 10 March 2017
  11. Drugbank (2018) GenomeCanada. Available at: https://www.drugbank.ca/drugs/DB00572. Accessed 26 March 2018
  12. Durdans hospital laboratory network (2018) Durdans hospital. Available at: https://www.durdans.com/lab-network/. Accessed 8 March 2018
  13. Elrick H, Stimmler L, Hlad CJ, Arai Y (1964) Plasma insulin response to oral and intravenous glucose administration. The Journal of clinical endocrinology and metabolism. J Clin Endocrinol Metab 24:1076–1082CrossRefGoogle Scholar
  14. Færch K, Torekov SS, Vistisen D, Johansen NB, Witte DR, Jonsson A, Pedersen O, Hansen T, Lauritzen T, Sandbæk A, Holst JJ, Jørgensen ME (2015) GLP-1 response to oral glucose is reduced in prediabetes, screen-detected type 2 diabetes, and obesity and influenced by sex: the ADDITION-PRO study. Diabetes 64(7):2513–2525CrossRefGoogle Scholar
  15. Fukuto TR (1990) Mechanism of action of organophosphorus and carbamate insecticides. Environ Health Perspect 87:245–254CrossRefGoogle Scholar
  16. Gifford R, Siribaddana S, Forbes S, Eddleston M (2015) Endocrine-disrupting chemicals and the diabetes epidemic in countries in the WHO South-East Asia region. Lancet Diabetes Endocrinol 3(12):925–927CrossRefGoogle Scholar
  17. Glucagon-Like Peptide-1 Total ELISA 96-Well Plate Assay (2013) EMD Millipore Corporation. Available at: http://www.merckmillipore.com/INTL/en/product/Multi-Species-GLP-1-Total-ELISA-EZGLP1T-36K,MM_NF-EZGLP1T-36K#anchor_PR. Accessed 26 February 2018
  18. GraphPad Prism 7 (2018) GraphPad software. Available at: https://www.graphpad.com. Accessed 8 March 2018
  19. Hectors TL, Vanparys C, van der Ven K, Martens GA, Jorens PG, Van Gaal LF, Covaci A, De Coen W, Blust R (2011) Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function. Diabetologia 54(6):1273–1290CrossRefGoogle Scholar
  20. Herrmann-Rinke C, Vöge A, Hess M, Göke B (1995) Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 147(1):25–31CrossRefGoogle Scholar
  21. Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 225:1409–1439CrossRefGoogle Scholar
  22. Idorn T, Knop FK, Jørgensen MB, Christensen M, Holst JJ, Hornum M, Feldt-Rasmussen B (2014) Elimination and degradation of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with end-stage renal disease. J Clin Endocrinol Metab 99(7):2457–2466CrossRefGoogle Scholar
  23. Joshi A K R and Rajini P S (2012) Organophosphorus insecticides and glucose homeostasis, In Perveen, F. (ed.) Insecticides-pest engineering. InTech, pp. 65 – 84.Google Scholar
  24. Karami-Mohajeri S, Abdollahi M (2011) Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum Exp Toxicol 30(9):1119–1140CrossRefGoogle Scholar
  25. Karuranga S, da Rocha Fernandes J, Huang Y, Malanda B (eds) (2017) IDF diabetes atlas. 8th edn, International Diabetes Federation, 8th edn. International Diabetes Federation, Brussels, BelgiumGoogle Scholar
  26. Katulanda P, Rathnapala DAV, Sheriff R, Matthews DR (2012) Province and ethnic specific prevalence of diabetes among Sri Lankan adults. Sri Lanka Journal of Diabetes Endocrinology and Metabolism 1(1):2–7CrossRefGoogle Scholar
  27. Katz K D (2015) Organophosphate toxicity workup: laboratory studies, imaging studies, electrocardiography, medscape. Available at: http://emedicine.medscape.com/article/167726-workup. Accessed 26 February 2018
  28. Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM (2013) Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia 56(4):696–708CrossRefGoogle Scholar
  29. Kuhre RE, Wewer Albrechtsen NJ, Hartmann B, Deacon CF, Holst JJ (2015) Measurement of the incretin hormones: glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. J Diabetes Complicat 29(3):445–450CrossRefGoogle Scholar
  30. Lasram MM, Dhouib IB, Annabi A, El Fazaa S, Gharbi N (2014) A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides. Toxicology 322:1–13CrossRefGoogle Scholar
  31. Lenhard A, Lenhard W (2017) Computation of effect sizes. PsychometricaGoogle Scholar
  32. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRefGoogle Scholar
  33. Li B, Duysen EG, Volpicelli-Daley LA, Levey AI, Lockridge O (2003) Regulation of muscarinic acetylcholine receptor function in acetylcholinesterase knockout mice. Pharmacol Biochem Behav 74(4):977–986CrossRefGoogle Scholar
  34. Mace OJ, Schindler M, Patel S (2012) The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine. J Physiol 590(12):2917–2936CrossRefGoogle Scholar
  35. Martin J (ed.) (2015) Oral glucose tolerance test, In British National Formulary. 68th edn. London: BMJ group, Pharmaceutical press, p. 480.Google Scholar
  36. McNab, C. (2006) WHO Pesticides are a leading suicide method, WHO Communications. Geneva: World Health Organization. Available at: http://www.who.int/mediacentre/news/notes/2006/np24/en/. Accessed 4 February 2018
  37. Montgomery MP, Kamel F, Saldana TM, Alavanja MC, Sandler DP (2008) Incident diabetes and pesticide exposure among licensed pesticide applicators: agricultural health study, 1993–2003. Am J Epidemiol 167(10):1235–1246CrossRefGoogle Scholar
  38. MultiskanTM FC Microplate Photometer (2018) Thermo Fisher Scientific. Available at: https://www.thermofisher.com/order/catalog/product/51119000. Accessed 8 March 2018
  39. National list of essential medicines. 6th edn (2013-2014) Ministry of Health, Sri Lanka. Colombo: Ministry of Health, Sri Lanka. Available at: http://nmra.gov.lk/images/pdf/final-book.pdf. Accessed 4 February 2018
  40. Nauck M, Stöckmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependet) diabetes. Diabetologia 29(1):46–52CrossRefGoogle Scholar
  41. Organophosphates (2018) WikiTox. Available at: http://curriculum.toxicology.wikispaces.net/2.2.7.4.5+Organophosphates. Accessed 26 February 2018
  42. Perley MJ, Kipnis DM (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. J Clin Invest 46(12):1954–1962CrossRefGoogle Scholar
  43. Precinorm U and Precipath U (2018) Roche Diagnostics USA. Available at: https://usdiagnostics.roche.com/combinedResult.html#/q/precinorm%2Bu%2Band%2Bprecipath%2Bu/rt/docs/s/SCORE_DESC. Accessed 8 March 2018
  44. Prins JB (2008) Incretin mimetics and enhancers: mechanisms of action. Aust Prescr 31:102–104CrossRefGoogle Scholar
  45. Rathish D, Jayasumana MACS (2017) An atlas of commonly used pesticides in Sri Lanka, 1st edn. Samudra book publications, AnuradhapuraGoogle Scholar
  46. Rathish D, Agampodi SB, Jayasumana MACS, Siribaddana SH (2016) From organophosphate poisoning to diabetes mellitus: the incretin effect. Med Hypotheses 91:53–55CrossRefGoogle Scholar
  47. Rathish D, Premarathna I, Jayathilake T, Kandegedara C, Punchihewa K, Ananda L, Bandara T, Jayasumana C, Siribaddana S (2017) Availability of essential medicines in selected public, primary and secondary health care institutions of a rural Sri Lankan district: a spot survey. BMC Health Serv Res 17(1):11CrossRefGoogle Scholar
  48. Scheen AJ (2003) Pathophysiology of type 2 diabetes. Acta Clin Belg 58(6):335–341CrossRefGoogle Scholar
  49. Seino Y, Fukushima M, Yabe D (2010) GIP and GLP-1, the two incretin hormones: similarities and differences. Journal of Diabetes Investigation 1(1-2):8–23CrossRefGoogle Scholar
  50. Senarathna L, Jayamanna SF, Kelly PJ, Buckley NA, Dibley MJ, Dawson AH (2012) Changing epidemiologic patterns of deliberate self poisoning in a rural district of Sri Lanka. BMC Public Health 12(1):593CrossRefGoogle Scholar
  51. Sigma-Aldrich, analytical reagents and solvents (2018) Merck KGaA, Darmstadt, Germany. Available at: https://www.sigmaaldrich.com/analytical-chromatography/analytical-reagents.html. Accessed 8 February 2018
  52. Singh AK (2015) Incretin response in Asian type 2 diabetes: are Indians different? Indian J Endocrinol Metab 19(1):30–38CrossRefGoogle Scholar
  53. Spectro 2000 (2001) Labomed, Inc, USA. Available at: http://www.labomed.com/2000rs.htm. Accessed 8 February 2018
  54. Stangroom J (2018) Kruskal-Wallis test calculator, Social science statistics. Available at: http://www.socscistatistics.com/tests/kruskal/Default.aspx. Accessed 8 March 2018
  55. Thayer KA, Heindel JJ, Bucher JR, Gallo MA (2012) Role of environmental chemicals in diabetes and obesity: a national toxicology program workshop review. Environ Health Perspect 120(6):779–789CrossRefGoogle Scholar
  56. Thomas S H L and White J (2014) Organophosphorus insecticides and nerve agents, In Walker BR, Colledge NR, Ralston SH, Penman ID (ed.) In Davidson’s principles and practice of medicine. 22nd edn Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto: Elsevier Limited, p. 220.Google Scholar
  57. Vale JA (1998) Toxicokinetic and toxicodynamic aspects of organophosphorus (OP) insecticide poisoning. Toxicol Lett 102-103:649–652CrossRefGoogle Scholar
  58. Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ (2001) Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 50(3):609–613CrossRefGoogle Scholar
  59. Worek, F (2013) Standard operation procedure - determination of cholinesterase status in whole blood and plasma. 4.1 edn. Munich.Google Scholar
  60. Worek F, Mast U, Kiderlen D, Diepold C, Eyer P (1999) Improved determination of acetylcholinesterase activity in human whole blood. Clin Chim Acta 288(1-2):73–90CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Devarajan Rathish
    • 1
  • Indika Senavirathna
    • 2
  • Channa Jayasumana
    • 1
  • Suneth Agampodi
    • 3
  • Sisira Siribaddana
    • 4
  1. 1.Department of Pharmacology, Faculty of Medicine and Allied SciencesRajarata University of Sri LankaSaliyapuraSri Lanka
  2. 2.Department of Biochemistry, Faculty of Medicine and Allied SciencesRajarata University of Sri LankaSaliyapuraSri Lanka
  3. 3.Department of Community Medicine, Faculty of Medicine and Allied SciencesRajarata University of Sri LankaSaliyapuraSri Lanka
  4. 4.Department of Medicine, Faculty of Medicine and Allied SciencesRajarata University of Sri LankaSaliyapuraSri Lanka

Personalised recommendations