Abstract
Six organochlorine pesticides and pesticide metabolites in human blood were tested to determine their relationships with diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 (unweighted, n=2992, population estimate=133,088,752). The six chemicals were p,p′-DDT (dichlorodiphenyltrichloroethane), p,p′-DDE (dichlorodiphenyltrichloroethylene), beta-hexachlorocyclohexane, oxychlordane, trans-nonachlor and heptachlor epoxide. In this research, total diabetes included diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥6.5%), and nephropathy was defined as a urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria. The pesticide p,p′-DDT and pesticide metabolite heptachlor epoxide were significantly associated with total diabetes with nephropathy, with odds ratios of 2.08 (95% CI 1.06–4.11) and 1.75 (95% CI 1.05–2.93), respectively. Organochlorine pesticides are thought to act through the constitutive androstane receptor/pregnane X receptor disease pathway, but this is not well established. When p,p′-DDT and heptachlor epoxide were both elevated, the odds ratio for diabetic nephropathy was 2.76 (95% CI 1.31–5.81), and when six of six organochlorine pesticides and pesticide metabolites, were elevated, the odds ratio for diabetic nephropathy was 3.00 (95% CI 1.08–8.36). The differences in the odds ratios for these groups appear to be due to differences in the mean heptachlor epoxide concentration of each category. Organochlorine pesticides and pesticide metabolites are known to have estrogenic, antiestrogenic or antiandrogenic activity. The constitutive androstane receptor/pregnane X receptor pathway is thought to interact with the aryl hydrocarbon receptor pathway, and the associations noted may be due to that interaction.
References
1. Edwards JR, Prozialeck WC. Cadmium, diabetes and chronic kidney disease. Toxicol Appl Pharmacol 2009;238:289–93.10.1016/j.taap.2009.03.007Search in Google Scholar PubMed PubMed Central
2. Haswell-Elkins M, Satarug S, O’Rourke P, Moore M, Ng J, et al. Striking association between urinary cadmium level and albuminuria among Torres Strait Islander people with diabetes. Environ Res 2008;106:379–83.10.1016/j.envres.2007.10.004Search in Google Scholar PubMed
3. Marchewka Z, Grzebinoga A. Chemical substances as risk factors of nephropathy in diabetes mellitus. Postepy Hig Med Dosw 2009;63:592–7.Search in Google Scholar
4. Obert DM, Hua P, Pilkerton ME, Feng W, Jaimes EA. Environmental tobacco smoke furthers progression of diabetic nephropathy. Am J Med Sci 2011;341:126–30.10.1097/MAJ.0b013e3181f6e3bfSearch in Google Scholar PubMed PubMed Central
5. Gennings C, Ellis R, Ritter JK. Linking empirical estimates of body burden of environmental chemicals and wellness using NHANES data. Environ Int 2012;39:56–65.10.1016/j.envint.2011.09.002Search in Google Scholar PubMed PubMed Central
6. Haws LC, Su SH, Harris M, DeVito MJ, Walker NJ, et al. Development of a refined database of mammalian relative potency estimates for dioxin-like compounds. Toxicol Sci 2006;89:4–30.10.1093/toxsci/kfi294Search in Google Scholar PubMed
7. Van den Berg M, Birnbaum LS, Denison M, DeVito M, Farland W, et al. The 2005 World Health Organization reevaluation of human and mammalian toxic equivalency factors for dioxins and dioxin-like compounds. Toxicol Sci 2006;93:223–41.10.1093/toxsci/kfl055Search in Google Scholar PubMed PubMed Central
8. Everett CJ, Thompson OM. Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy? Environ Res 2014;132:126–31.10.1016/j.envres.2014.03.043Search in Google Scholar PubMed
9. Lee CC, Yao YJ, Chen HL, Guo YL, Su HJ. Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs levels in Taiwan. J Toxicol Environ Health A 2006;69:367–80.10.1080/15287390500244972Search in Google Scholar PubMed
10. Casals-Casas C, Desvergne B. Endocrine disruptors: from endocrine to metabolic disruption. Annu Rev Physiol 2011;73:135–62.10.1146/annurev-physiol-012110-142200Search in Google Scholar PubMed
11. Lee DH, Porta M, Jacobs DR Jr., Vandenberg LN. Chlorinated persistent organic pollutants, obesity and type 2 diabetes. Endocr Rev 2014;35:557–601.10.1210/er.2013-1084Search in Google Scholar PubMed PubMed Central
12. Centers for Disease Control and Prevention (CDC). Third national report on human exposure to environmental chemicals. Atlanta: National Center for Environmental Health, 2005: NCEH Pub No 05-0570, 467pp.Search in Google Scholar
13. Everett CJ, Matheson EM. Biomarkers of pesticide exposure and diabetes in the 1999-2004 National Health and Nutrition Examination Survey. Environ Int 2010;36:398–401.10.1016/j.envint.2010.02.010Search in Google Scholar PubMed
14. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. National Health and Nutrition Examination Survey, NHANES 1999-2004. Available at: http://www.cdc.gov/nchs/nhanes.htm.Search in Google Scholar
15. Molitch ME, DeFronzo RA, Franz MJ, Keane WF, Mogensen CE, et al. American Diabetes Association. Nephropathy in diabetes. Diabetes Care 2004;27(Suppl 1):S79–83.10.2337/diacare.27.2007.S79Search in Google Scholar PubMed
16. American Diabetes Association (ADA). Summary of revisions for the 2010 clinical practice recommendations. Diabetes Care 2010;33(Suppl 1):S3.10.2337/dc10-S003Search in Google Scholar PubMed PubMed Central
17. Schisterman EF, Whitcomb BW, Louis GM, Louis TA. Lipid adjustment in the analysis of environmental contaminants and human health risks. Environ Health Perspect 2005;113:853–57.10.1289/ehp.7640Search in Google Scholar PubMed PubMed Central
18. SAS Institute Inc. SAS version 9.3, 2014: Cary, North Carolina, USA.Search in Google Scholar
19. Everett CJ. Commentary on nephropathy and longitudinal studies of diabetes and dioxins, furans, and dioxin-like PCBs. Environ Res 2014;134:8.10.1016/j.envres.2014.06.020Search in Google Scholar PubMed
©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Exposure to and health effects of volatile PCBs
- Association of DDT and heptachlor epoxide in human blood with diabetic nephropathy
- Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action
- The 2008/2009 cholera outbreak in Harare, Zimbabwe: case of failure in urban environmental health and planning
- Development of banana-based weaning food mixes for infants and its nutritional quality evaluation
Articles in the same Issue
- Frontmatter
- Exposure to and health effects of volatile PCBs
- Association of DDT and heptachlor epoxide in human blood with diabetic nephropathy
- Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action
- The 2008/2009 cholera outbreak in Harare, Zimbabwe: case of failure in urban environmental health and planning
- Development of banana-based weaning food mixes for infants and its nutritional quality evaluation