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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2021; 12(11): 1818-1831
Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1818
Organophosphate pesticides and new-onset diabetes mellitus: From molecular mechanisms to a possible therapeutic perspective
Ya-Ling Chung, Yi-Chou Hou, I-Kuan Wang, Kuo-Cheng Lu, Tzung-Hai Yen
Ya-Ling Chung, Department of Medical Laboratory, Cardinal-Tien Hospital, New Taipei City 231, Taiwan
Yi-Chou Hou, Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City 231, Taiwan
Yi-Chou Hou, Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Yi-Chou Hou, Kuo-Cheng Lu, School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
I-Kuan Wang, Department of Nephrology, China Medical University Hospital, Taichung 404, Taiwan
I-Kuan Wang, College of Medicine, China Medical University, Taichung 404, Taiwan
Kuo-Cheng Lu, Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, New Taipei City 242, Taiwan
Kuo-Cheng Lu, Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
Tzung-Hai Yen, Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan
Tzung-Hai Yen, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Author contributions: Chung YL and Hou YC contributed data collection and manuscript writing; Wang IK contributed data analysis; Lu KC and Yen TH contributed study design and supervision; Chung YL and Hou YC contributed equally to this work; Lu KC and Yen TH also contributed equally.
Supported by Chang Gung Memorial Hospital, Linkou, Taiwan, No. CORPG3K0191 and No. CMRPG3J1051-3.
Conflict-of-interest statement: The authors declare no conflicts of financial interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Tzung-Hai Yen, MD, PhD, Doctor, Professor, Department of Nephrology, Chang Gung Memorial Hospital, No. 199 Tung Hwa North Road, Linkou 333, Taiwan. m19570@adm.cgmh.org.tw
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: May 3, 2021
Revised: May 27, 2021
Accepted: September 22, 2021
Article in press: September 22, 2021
Published online: November 15, 2021
Abstract

Organophosphate is a commonly used pesticide in the agricultural sector. The main action of organophosphate focuses on acetylcholinesterase inhibition, and it therefore contributes to acute cholinergic crisis, intermediate syndrome and delayed neurotoxicity. From sporadic case series to epidemiologic studies, organophosphate has been linked to hyperglycemia and the occurrence of new-onset diabetes mellitus. Organophosphate-mediated direct damage to pancreatic beta cells, insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of new-onset diabetes mellitus. To date, a preventive strategy for organophosphate-mediated new-onset diabetes mellitus is still lacking. However, lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.

Keywords: Organophosphate, Pesticide, New-onset diabetes mellitus, Mechanism, Reactive oxygen species

Core Tip: Organophosphate may induce acute hyperglycemia by damaging pancreatic cells and result in new-onset diabetes mellitus after chronic exposure to organophosphate compounds. Organophosphate-mediated new-onset diabetes mellitus might be mediated by a polymorphism of paraoxonase-1, which is associated with organophosphate elimination in hepatocytes. Pancreatic beta cell damage, excessive gluconeogenesis, hepatic steatosis, systemic inflammation and possibly sarcopenia all contribute to insulin resistance and therefore hyperglycemia.