A Systematic Review on Organophosphate Pesticide and Type II Diabetes Mellitus

Author(s): Jothi Lakshmi, Krishnendu Mukhopadhyay*, Padmavathi Ramaswamy, Shriraam Mahadevan

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 6 , 2020

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Organophosphate (OP) pesticides are extremely poisonous and they affect the glucose breakdown in numerous and mechanism. There are higher evidence of stimulating diabetes mellitus through OP pesticides especially the type II diabetes. The upsurge in the level of glucose (hyperglycemia), and insulin resistance along with their related outcomes are discussed in this review. The data related to investigational and clinical techniques endorse a connection amid such molecular mechanism and compounds of OPs. Numerous studies conducted till March 2018 have reported OP’ exposures and diabetes-related outcomes. The acute and chronic exposure in case of these insecticides and diabetesrelated outcomes are defined in this study. Initially, it was declared that OPs prompt to hyperglycemia. Then, a high association of glucose in blood beside insulin was found out. The affirmation from some clinical as well as investigational studies supported a connection amid exposure to OP and diabetes, yet in maximum number of instances, non-specific diabetes occurs.

Keywords: Diabetes mellitus, glucose metabolism, organophosphates, pesticides, type-II diabetes mellitus.

Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94(3): 311-21.
[http://dx.doi.org/10.1016/j.diabres.2011.10.029] [PMID: 22079683]
Hansen MR, Jørs E, Lander F, Condarco G, Schlünssen V. Is cumulated pyrethroid exposure associated with prediabetes? A cross-sectional study. J Agromed 2014; 19(4): 417-26.
[http://dx.doi.org/10.1080/1059924X.2014.945708] [PMID: 25275407]
Juntarawijit C, Juntarawijit Y. Association between diabetes and pesticides: a case-control study among Thai farmers. Environ Health Prev Med 2018; 23(1): 3.
[http://dx.doi.org/10.1186/s12199-018-0692-5] [PMID: 29374457]
Campbell A, Chapman M. Handbook of poisoning in dogs and cats. 2008.
Rahimi R, Abdollahi M. A review on the mechanisms involved in hyperglycemia induced by organophosphorus pesticides. Pestic Biochem Physiol 2007; 88: 115-21.
Juntarawijit C, Juntarawijit Y. Association between diabetes and pesticides: a case-control study among Thai farmers. Environ Health Prev Med 2018; 23(1): 3.
[http://dx.doi.org/10.1186/s12199-018-0692-5] [PMID: 29374457]
Rathish D, Agampodi SB, Jayasumana MACS, Siribaddana SH. From organophosphate poisoning to diabetes mellitus: The incretin effect. Med Hypotheses 2016; 91: 53-5.
[http://dx.doi.org/10.1016/j.mehy.2016.04.002] [PMID: 27142144]
Saldana TM, Basso O, Hoppin JA, et al. Pesticide exposure and self-reported gestational diabetes mellitus in the Agricultural Health Study. Diabetes Care 2007; 30(3): 529-34.
[http://dx.doi.org/10.2337/dc06-1832] [PMID: 17327316]
Starling AP, Umbach DM, Kamel F, Long S, Sandler DP, Hoppin JA. Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study. Occup Environ Med 2014; 71(9): 629-35.
[http://dx.doi.org/10.1136/oemed-2013-101659] [PMID: 24727735]
Pajoumand A, Jalali N, Abdollah M, Shadnia S. Survival following severe aluminium phosphide poisoning. Journal of Pharmacy Practice and Research 2002; 32: 297-9.
Anini Y, Hansotia T, Brubaker PL. Muscarinic receptors control postprandial release of glucagon-like peptide-1: in vivo and in vitro studies in rats. Endocrinology 2002; 143(6): 2420-6.
[http://dx.doi.org/10.1210/endo.143.6.8840] [PMID: 12021207]
Anini Y, Brubaker PL. Muscarinic receptors control glucagon-like peptide 1 secretion by human endocrine L cells. Endocrinology 2003; 144(7): 3244-50.
[http://dx.doi.org/10.1210/en.2003-0143] [PMID: 12810581]
Lasram MM, Dhouib IB, Annabi A, El Fazaa S, Gharbi N. A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides. Toxicology 2014; 322: 1-13.
[http://dx.doi.org/10.1016/j.tox.2014.04.009] [PMID: 24801903]
Thayer KA, Heindel JJ, Bucher JR, Gallo MA. Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ Health Perspect 2012; 120(6): 779-89.
[http://dx.doi.org/10.1289/ehp.1104597] [PMID: 22296744]
Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin hormones: Similarities and differences. J Diabetes Investig 2010; 1(1-2): 8-23.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00022.x] [PMID: 24843404]
Duttaroy A, Zimliki CL, Gautam D, Cui Y, Mears D, Wess J. Muscarinic stimulation of pancreatic insulin and glucagon release is abolished in m3 muscarinic acetylcholine receptor-deficient mice. Diabetes 2004; 53(7): 1714-20.
[http://dx.doi.org/10.2337/diabetes.53.7.1714] [PMID: 15220195]
Novelli M, Piaggi S, De Tata V. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced impairment of glucose-stimulated insulin secretion in isolated rat pancreatic islets. Toxicol Lett 2005; 156(2): 307-14.
[http://dx.doi.org/10.1016/j.toxlet.2004.12.004] [PMID: 15737493]
Pourkhalili N, Pournourmohammadi S, Rahimi F, et al. Comparative effects of calcium channel blockers, autonomic nervous system blockers, and free radical scavengers on diazinon-induced hyposecretion of insulin from isolated islets of Langerhans in rats. Arh Hig Rada Toksikol 2009; 60(2): 157-64.
[http://dx.doi.org/10.2478/10004-1254-60-2009-1917] [PMID: 19581208]
Singh M, Sandhir R, Kiran R. Erythrocyte antioxidant enzymes in toxicological evaluation of commonly used organophosphate pesticides 2006.
Karami-Mohajeri S, Abdollahi M. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum Exp Toxicol 2011; 30(9): 1119-40.
[http://dx.doi.org/10.1177/0960327110388959] [PMID: 21071550]
Kamath V, Rajini PS. Altered glucose homeostasis and oxidative impairment in pancreas of rats subjected to dimethoate intoxication. Toxicology 2007; 231(2-3): 137-46.
[http://dx.doi.org/10.1016/j.tox.2006.11.072] [PMID: 17197067]
Hagar HH, Azza H , Fahmy . A biochemical, histochemical, and ultrastructural evaluation of the effect of dimethoate intoxication on rat pancreas. Toxicol Lett 2002; 133(2-3): 161-70.
[http://dx.doi.org/10.1016/S0378-4274(02)00128-5] [PMID: 12119124]
Bretaud S, Saglio P, Saligaut C, Auperin B. Biochemical and behavioral effects of carbofuran in goldfish (Carassius auratus). Environ Toxicol Chem 2002; 21(1): 175-81.
[http://dx.doi.org/10.1002/etc.5620210125] [PMID: 11804052]
Lo AC, Soliman AS, El-Ghawalby N, et al. Lifestyle, occupational, and reproductive factors in relation to pancreatic cancer risk. Pancreas 2007; 35(2): 120-9.
[http://dx.doi.org/10.1097/mpa.0b013e318053e7d3] [PMID: 17632317]
Abdollahi M, Donyavi M, Pournourmohammadi S, Saadat M. Hyperglycemia associated with increased hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase in rats following subchronic exposure to malathion. Comp Biochem Physiol C Toxicol Pharmacol 2004; 137(4): 343-7.
[http://dx.doi.org/10.1016/j.cca.2004.03.009] [PMID: 15228952]
Basiri S, Esmaily H, Vosough-Ghanbari S, Mohammadirad A, Yasa N, Abdollahi M. Improvement by Saturejakhuzestanica essential oil of malathion-induced red blood cells acetylcholinesterase inhibition and altered hepatic mitochondrial glycogen phosphorylase and phosphoenolpyruvate carboxykinase activities. Pestic Biochem Physiol 2007; 89: 124-9.
Rezg R, Mornagui B, El-Fazaa S, Gharbi N. Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity. Toxicology 2008; 250(1): 27-31.
[http://dx.doi.org/10.1016/j.tox.2008.05.017] [PMID: 18588939]
Rezg R, Mornagui B, El-Arbi M, Kamoun A, El-Fazaa S, Gharbi N. Effect of subchronic exposure to malathion on glycogen phosphorylase and hexokinase activities in rat liver using native PAGE. Toxicology 2006; 223(1-2): 9-14.
[http://dx.doi.org/10.1016/j.tox.2006.02.020] [PMID: 16621213]
Adigun AA, Wrench N, Seidler FJ, Slotkin TA. Neonatal organophosphorus pesticide exposure alters the developmental trajectory of cell-signaling cascades controlling metabolism: differential effects of diazinon and parathion. Environ Health Perspect 2010; 118(2): 210-5.
[http://dx.doi.org/10.1289/ehp.0901237] [PMID: 20123610]
Begum G. Carbofuran insecticide induced biochemical alterations in liver and muscle tissues of the fish Clarias batrachus (linn) and recovery response. Aquat Toxicol 2004; 66(1): 83-92.
[http://dx.doi.org/10.1016/j.aquatox.2003.08.002] [PMID: 14687981]
Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR Jr. Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002. Diabetologia 2007; 50(9): 1841-51.
[http://dx.doi.org/10.1007/s00125-007-0755-4] [PMID: 17624515]
Meggs WJ, Brewer KL. Weight gain associated with chronic exposure to chlorpyrifos in rats. J Med Toxicol 2007; 3(3): 89-93.
[http://dx.doi.org/10.1007/BF03160916] [PMID: 18072142]
Lassiter TL, Ryde IT, Mackillop EA, et al. Exposure of neonatal rats to parathion elicits sex-selective reprogramming of metabolism and alters the response to a high-fat diet in adulthood. Environ Health Perspect 2008; 116(11): 1456-62.
[http://dx.doi.org/10.1289/ehp.11673] [PMID: 19057696]
Rezg R, Mornagui B, El-Fazaa S, Gharbi N. Organophosphorus pesticides as food chain contaminants and type 2 diabetes: a review. Trends Food Sci Technol 2010; 21: 345-57.
Lee WJ, Chong K, Lee YC, et al. Effects of obesity surgery on type 2 diabetes mellitus Asian patients. World J Surg 2009; 33(9): 1895-903.
[http://dx.doi.org/10.1007/s00268-009-0115-2] [PMID: 19603228]
Lassiter TL, Brimijoin S. Rats gain excess weight after developmental exposure to the organophosphorothionate pesticide, chlorpyrifos. Neurotoxicol Teratol 2008; 30(2): 125-30.
[http://dx.doi.org/10.1016/j.ntt.2007.10.004] [PMID: 18166376]
Slotkin TA, Lassiter TL, Ryde IT, Wrench N, Levin ED, Seidler FJ. Consumption of a high-fat diet in adulthood ameliorates the effects of neonatal parathion exposure on acetylcholine systems in rat brain regions. Environ Health Perspect 2009; 117(6): 916-22.
[http://dx.doi.org/10.1289/ehp.0800459] [PMID: 19590683]
Montgomery MP, Kamel F, Saldana TM, Alavanja MC, Sandler DP. Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study, 1993-2003. Am J Epidemiol 2008; 167(10): 1235-46.
[http://dx.doi.org/10.1093/aje/kwn028] [PMID: 18343878]
Pournourmohammadi S, Farzami B, Ostad SN, Azizi E, Abdollahi M. Effects of malathion subchronic exposure on rat skeletal muscle glucose metabolism. Environ Toxicol Pharmacol 2005; 19(1): 191-6.
[http://dx.doi.org/10.1016/j.etap.2004.07.002] [PMID: 21783476]
Carmena R. Type 2 diabetes, dyslipidemia, and vascular risk: rationale and evidence for correcting the lipid imbalance. Am Heart J 2005; 150(5): 859-70.
[http://dx.doi.org/10.1016/j.ahj.2005.04.027] [PMID: 16290951]
Pinget M, Boullu-Sanchis S. Physiological basis of insulin secretion abnormalities 2002.
Poitout V, Robertson RP. Minireview: Secondary β-cell failure in type 2 diabetes--a convergence of glucotoxicity and lipotoxicity. Endocrinology 2002; 143(2): 339-42.
[http://dx.doi.org/10.1210/endo.143.2.8623] [PMID: 11796484]
Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care 2007; 10(2): 142-8.
[http://dx.doi.org/10.1097/MCO.0b013e328042ba90] [PMID: 17285001]
Bomser JA, Quistad GB, Casida JE. Chlorpyrifos oxon potentiates diacylglycerol-induced extracellular signal-regulated kinase (ERK 44/42) activation, possibly by diacylglycerol lipase inhibition. Toxicol Appl Pharmacol 2002; 178(1): 29-36.
[http://dx.doi.org/10.1006/taap.2001.9324] [PMID: 11781077]
Sarkar R, Mohanakumar KP, Chowdhury M. Effects of an organophosphate pesticide, quinalphos, on the hypothalamo-pituitary-gonadal axis in adult male rats. J Reprod Fertil 2000; 118(1): 29-38.
[http://dx.doi.org/10.1530/jrf.0.1180029] [PMID: 10793623]
Rezg R, Mornagui B, Benahmed M, et al. Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats. Food Chem Toxicol 2010; 48(6): 1473-7.
[http://dx.doi.org/10.1016/j.fct.2010.03.013] [PMID: 20233601]
Clement JG. Hormonal consequences of organophosphate poisoning. Fundam Appl Toxicol 1985; 5(6 Pt 2): S61-77.
[http://dx.doi.org/10.1016/0272-0590(85)90115-0] [PMID: 3005101]
Liang Y, Osborne MC, Monia BP, et al. Antisense oligonucleotides targeted against glucocorticoid receptor reduce hepatic glucose production and ameliorate hyperglycemia in diabetic mice. Metabolism 2005; 54(7): 848-55.
[http://dx.doi.org/10.1016/j.metabol.2005.01.030] [PMID: 15988691]
Meller D, Fraser I, Kryger M. Hyperglycemia in anticholinesterase poisoning. Can Med Assoc J 1981; 124(6): 745-8.
[PMID: 7471018]
Liu SH, Lin JL, Shen HL, et al. Acute large-dose exposure to organophosphates in patients with and without diabetes mellitus: analysis of mortality rate and new-onset diabetes mellitus. Environ Health 2014; 13(1): 11.
[http://dx.doi.org/10.1186/1476-069X-13-11] [PMID: 24597539]
Badrane N, Askour M, Berechid K, Abidi K, Dendane T, Zeggwagh AA. Severe oral and intravenous insecticide mixture poisoning with diabetic ketoacidosis: a case report. BMC Res Notes 2014; 7: 485.
[http://dx.doi.org/10.1186/1756-0500-7-485] [PMID: 25078103]
Swaminathan K, Thangavel G. Pesticides and human diabetes: a pilot project to explore a possible link. Pract Diabetes 2015; 32: 111-3.
Debost-Legrand A, Warembourg C, Massart C, et al. Prenatal exposure to persistent organic pollutants and organophosphate pesticides, and markers of glucose metabolism at birth. Environ Res 2016; 146: 207-17.
[http://dx.doi.org/10.1016/j.envres.2016.01.005] [PMID: 26775002]
Raafat N, Abass MA, Salem HM. Malathion exposure and insulin resistance among a group of farmers in Al-Sharkia governorate. Clin Biochem 2012; 45(18): 1591-5.
[http://dx.doi.org/10.1016/j.clinbiochem.2012.07.108] [PMID: 22885474]
Rezg R, Mornagui B, El-Fazaa S, Gharbi N. Organophosphorus pesticides as food chain contaminants and type 2 diabetes: a review. Trends Food Sci Technol 2010; 21: 345-57.
Park J, Park SK, Choi YH. Environmental pyrethroid exposure and diabetes in U.S. adults. Environ Res 2019; 172: 399-407.
[http://dx.doi.org/10.1016/j.envres.2018.12.043] [PMID: 30825691]
Shrestha S, Parks CG, Goldner WS, et al. Pesticide use and incident hyperthyroidism in farmers in the Agricultural Health Study 2019.
Rathish D, Senavirathna I, Jayasumana C, Agampodi S, Siribaddana S. 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. Environ Sci Pollut Res Int 2019; 26(3): 2864-72.
[http://dx.doi.org/10.1007/s11356-018-3818-9] [PMID: 30499084]
Shrestha S, Kumar Singh V, Kumar Sarkar S, Shanmugasundaram B, Jeevaratnam K, Chandra Koner B. Effect of sub-toxic exposure to Malathion on glucose uptake and insulin signaling in L6 myoblast derived myotubes. Drug Chem Toxicol 2018; •••: 1-8.
[http://dx.doi.org/10.1080/01480545.2018.1531881] [PMID: 30486685]
Chuang MC, Chang CH, Lee CS, et al. One-year mortality among hospital survivors of cholinesterase inhibitor poisoning based on Taiwan National Health Insurance Research Database from 2003 to 2012. BMC Pharmacol Toxicol 2018; 19(1): 72.
[http://dx.doi.org/10.1186/s40360-018-0263-9] [PMID: 30424813]
Shrestha S, Parks CG, Goldner WS, et al. Pesticide use and incident hypothyroidism in pesticide applicators in the Agricultural Health Study. Environ Health Perspect 2018; 126(9): 97008.
[http://dx.doi.org/10.1289/EHP3194] [PMID: 30256155]
Paul KC, Jerrett M, Ritz B. Type 2 diabetes mellitus and alzheimer’s disease: overlapping biologic mechanisms and environmental risk factors. Curr Environ Health Rep 2018; 5(1): 44-58.
[http://dx.doi.org/10.1007/s40572-018-0176-1] [PMID: 29464502]
Arrebola JP, Pumarega J, Gasull M, et al. Adipose tissue concentrations of persistent organic pollutants and prevalence of type 2 diabetes in adults from Southern Spain. Environ Res 2013; 122: 31-7.
[http://dx.doi.org/10.1016/j.envres.2012.12.001] [PMID: 23290489]

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Year: 2020
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