A Review of Mechanisms Which May Explain the Positive Epidemiologic Association of Organochlorines with Type 2 Diabetes
Main Article Content
Mary Beth Dail
http://orcid.org/0000-0001-6767-979X
Janice E. Chambers
http://orcid.org/0000-0002-7826-7042
http://orcid.org/0000-0001-6767-979X
Janice E. Chambers
http://orcid.org/0000-0002-7826-7042
Abstract
The Stockholm Convention on Persistent Organic Pollutants eliminated the production, use, and/or emissions of persistent pollutants which include organochlorines. Banned organochlorines are resistant to biodegradation and are therefore still present in soil, air, and water. They are lipophilic and bioaccumulate up the food chain so the major source of human exposure comes from fatty food. More than 40 epidemiological studies have indicated a positive association of organochlorines with type 2 diabetes but the data are insufficient to establish causality since most studies are case-control and cross-sectional where temporal associations cannot be determined. Also, some epidemiological studies have reported negative associations where organochlorine concentrations were lower in diabetics than controls and others showed inconsistencies across different populations or geographic areas. Because cross-sectional studies are prone to such biases, prospective studies were indicated. Most of these cohort prospective studies were not population based and had such small numbers of diabetics that the odds ratios’ confidence intervals were large enough to engender uncertainty. It has also been suggested that obesity or diabetes may increase the level of organochlorines (reverse causation) rather than high levels leading to disease (causation). In addition, non-monotonic dose-response relationships have been reported between organochlorines and metabolic syndrome endpoints such as impaired insulin action, triglyceride levels, and type 2 diabetes prevalence. Concerns like these reinforce the need to move away from epidemiological studies and toward mechanistic research to determine whether the association between organochlorines and type 2 diabetes is causal. To this end, a literature review was conducted searching for publications suggesting mechanisms for the positive association. The most interesting mechanisms are described in detail. In addition to describing the evidence for possible mechanisms, various concerns and suggestions are discussed.
Keywords:
organochlorine, type 2 diabetes, positive epidemiologic association, mechanism of action, metabolic dysregulation, insulin signaling dysregulation
Article Details
How to Cite
DAIL, Mary Beth; CHAMBERS, Janice E..
A Review of Mechanisms Which May Explain the Positive Epidemiologic Association of Organochlorines with Type 2 Diabetes.
Medical Research Archives, [S.l.], v. 14, n. 1, jan. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7218>. Date accessed: 03 feb. 2026.
doi: https://doi.org/10.18103/mra.v14i1.7218.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Taylor KW, Novak RF, Anderson HA, et al. Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: A National Toxicology Program Workshop review. Environ Health Perspect. 2013;121:774-783.
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6. Magliano DJ, Rancière F, Slama R, et al. Exposure to persistent organic pollutants and the risk of type 2 diabetes: A case-cohort study. Diabetes Metab. 2021;47:101234.
7. Petrlik J, Bell L, DiGangi J, et al. Monitoring dioxins and PCBs in eggs as sensitive indicators for environmental pollution and global contaminated sites and recommendations for reducing and controlling releases and exposure. Emer Contam. 2022;8:254-279.
8. Mondal T, Loffredo CA, Trnovec T, et al. Gene expression signatures in PCB‑exposed Slovak children in relation to their environmental exposures and socio‑physical characteristics. Environ Sci Pollut Res Int. 2022;40:60531-60541.
9. Russell EP. The strange career of DDT: Experts, federal capacity, and environmentalism in World War II. Technol Cult. 1999;40:770-796.
10. Meade MS. The rise and demise of malaria: Some reflections on southern settlement and landscape. Southeast Geogr. 1980;20:77-99.
11. Rogan WJ, Chen A. Health risks and benefits of bis (4-chlorophenyl)-1,1,1-trichloroethane (DDT). The Lancet. 2005;366:763-773.
12. Langer P, Kočan A, Tajtáková M, et al. Adverse health effects of heavy industrial and agricultural pollution in Eastern Slovakia. In: Newbury H, De Lorne W, eds. Industrial Pollution Including Oil Spills. Air, Water and Soil Pollution Science and Technology Series. Nova Science Publishers, Inc.; 2009:145-183.
13. Zhang C, Liu L, Ma Y, Li F. Using isomeric and metabolic ratios of DDT to identify the sources and fate of DDT in Chinese agricultural topsoil. Environ Sci Tech. 2018;52:1990-1996.
14. Hagen PE, Walls MP. The Stockholm Convention on persistent organic pollutants. Nat Resour Env. 2005;19:49-52.
15. Berg H. Global status of DDT and its alternatives for use in vector control to prevent disease. Environ Health Perspect. 2009;117:1656-1663.
16. World Health Organization. Malaria. Published December 4, 2023. Accessed December 11, 2024. http://www.WHO.int/news-room/fact-sheets/detail/malaria.
17. Ward A, Dail M, Meek E, Chambers JE. DDE blood levels and health of a unique rural population of African American females residing in the Mississippi Delta of the United States of America. Int J Environ Stud. 2023;80:1108-1125.
18. International Diabetes Federation. IDF Diabetes Atlas:10th ed. International Diabetes Federation; 2021.
19. Evangelou E, Ntritsos G, Chondrogiorgi M, et al. Exposure to pesticides and diabetes: A systematic review and meta-analysis. Environ Int. 2016;91:60-68.
20. Wei Y, Wang L, Liu J. The diabetogenic effects of pesticides: Evidence based on epidemiological and toxicological studies. Environ Pollut. 2023;331: 121927.
21. Cordier S, Anassour-Laouan-Sidia E, Lemirea M, Costet N, Lucasa M, Ayottea P. Association between exposure to persistent organic pollutants and mercury, and glucose metabolism in two Canadian Indigenous populations. Environ Res. 2020;184:109345.
22. Kerger BD, Scott PK, Pavuk M, Gough M, Paustenbach DJ. Re-analysis of Ranch Hand study supports reverse causation hypothesis between dioxin and diabetes. Crit Rev Toxicol. 2012;42:669-687.
23. Lee DH, Porta M, Jacobs DR Jr, Vandenberg LN. Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. Endocr Rev. 2014;35:557-601.
24. Meek EC, Jones DD, Crow JA, Wills RA, Cooke III WH, Chambers JE. Association of serum levels of p,p’-Dichlorodiphenyldichloroethylene (DDE) with type 2 diabetes in African American and Caucasian adult men from agricultural (Delta) and nonagricultural (non-Delta) regions of Mississippi. J Toxicol Environ Health A. 2019;82:387-400.
25. Mahmood A, Agarwal N, Sanyal S, Dudeja PK, Subrahmanyam D. Alterations in the intestinal brush border membrane structure and function in chronic DDT-exposed monkeys. Pestic Biochem Physiol. 1979;12:141-146.
26. Ghosh S, Mitra PS, Loffredo CA, et al. Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: Indicator of disease and disorder development in humans. Environ Res. 2015;138:202-216.
27. Moreira BP, Silva JF, Jarak I, Pereira ML, Oliveira PF, Alves MG. Technical-grade chlordane compromises rat Sertoli cells proliferation, viability and metabolic activity. Toxicol In Vitro. 2020;63:104673.
28. Park CM, Kim KT, Rhyu DY. Exposure to a low concentration of mixed organochlorine pesticides impairs glucose metabolism and mitochondrial function in L6 myotubes and zebrafish. J Hazard Mater. 2021;414:125437.
29. Lee H, Gao Y, Kim JK, et al. Synergetic effects of concurrent chronic exposure to a mixture of OCPs and high-fat diets on type 2 diabetes and beneficial effects of caloric restriction in female zebrafish. J Hazard Mater. 2023;446:130659.
30. Ibrahim MM, Fjære E, Lock EJ, et al. Metabolic impacts of high dietary exposure to persistent organic pollutants in mice. Toxicol Lett. 2012;215:8-15.
31. Jørgensen ME, Borch-Johnsen K, Bjerregaard P. A cross-sectional study of the association between persistent organic pollutants and glucose intolerance among Greenland Inuit. Diabetologia. 2008;51:1416-1422.
32. Howell GE III, Mulligan C, Meek E, Chambers JE. Effect of chronic p,p´-dichlorodiphenyldichloroethylene (DDE) exposure on high fat diet-induced alterations in glucose and lipid metabolism in male C57BL/6H mice. Toxicology. 2015;328:112-122.
33. Arab A, Mostafalou S. Pesticides and insulin resistance-related metabolic diseases: Evidences and mechanisms. Pestic Biochem Physiol. 2023;195:105521.
34. Baumert BO, Goodrich JA, Hu X, et al. Plasma concentrations of lipophilic persistent organic pollutants and glucose homeostasis in youth populations. Environ Res. 2022;212:113296.
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