Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case-control study

Duk-Hee Lee, Michael W Steffes, Andreas Sjödin, Richard S Jones, Larry L Needham, David R Jacobs Jr, Duk-Hee Lee, Michael W Steffes, Andreas Sjödin, Richard S Jones, Larry L Needham, David R Jacobs Jr

Abstract

Background: Low doses of some persistent organic pollutants (POPs) associate cross-sectionally with type 2 diabetes, whereas associations with high POP exposures are inconsistent.

Objectives: We investigated whether several POPs prospectively predict type 2 diabetes within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort.

Methods: Participants in this nested case-control study were diabetes free in 1987-1988. By 2005-2006, the 90 controls remained free of diabetes, whereas the 90 cases developed diabetes. Using serum collected in 1987-1988, we measured 8 organochlorine pesticides, 22 polychlorinated biphenyl congeners (PCBs), and 1 polybrominated biphenyl (PBB). We compared POP concentrations from CARDIA and the National Health and Nutrition Examination Survey (NHANES) in 2003-2004. We computed odds ratios (ORs) for incident diabetes using logistic regression analysis.

Results: Chlorinated POPs in CARDIA in 1987-1988 were much higher than corresponding NHANES 2003-2004 concentrations. POPs showed nonlinear associations with diabetes risk. The highest risk was observed in the second quartiles of trans-nonachlor, oxychlordane, mirex, highly chlorinated PCBs, and PBB153-a finding that suggests low-dose effects. We concentrated risk by summing these POPs and isolated very low concentrations of multiple POPs in the lowest sextile of the sum. The adjusted OR in the second sextile vs. the lowest sextile was 5.3 overall and 20.1 for body mass index > or = 30 kg/m2.

Conclusions: Several POPs at low doses similar to current exposure levels may increase diabetes risk, possibly through endocrine disruption. Certain POPs may a play a role in the current epidemic of diabetes, which has been attributed to obesity.

Figures

Figure 1
Figure 1
Adjusted ORs and 95% CIs of incident diabetes according to sextiles of the summary measure formed from serum concentrations of all 31 POPs (∑31POPs; A) or 16 selected POPs [∑16POPs; B) (trans-nonachlor + oxychlordane + mirex + PBB153 + 12 PCBs) with ORs ≥ 1.5 in the second quartile in Tables 3 and 4. Lipid-adjusted model, that is, adjusted for age, sex, race, BMI, triglycerides, and total cholesterol at year 2. *Significantly different from 1, p < 0.05.
Figure 2
Figure 2
Adjusted ORs and 95% CIs of incident diabetes according to sextiles of the summary measure formed from serum concentrations of all 31 POPs (∑31POPs; A, B) or 16 selected POPs (∑16POPs; C, D) (trans-nonachlor + oxychlordane + mirex + PBB153 + 12 PCBs) with ORs ≥ 1.5 in the second quartile in Tables 3 and 4 stratified by year 2 BMI. Lipid-adjusted model, that is, adjusted for age, sex, race, BMI, triglycerides, and total cholesterol at year 2. *Significantly different from 1, p < 0.05.

References

    1. Centers for Disease Control and Prevention (CDC) National Health and Nutrition Examination Survey: NHANES 2003–2004. 2010. [[accessed 20 July 2010]]. Available: .
    1. Daston GP, Cook JC, Kavlock RJ. Uncertainties for endocrine disrupters: our view on progress. Toxicol Sci. 2003;74(2):245–252.
    1. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Jr, et al. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41(11):1105–1116.
    1. Henriksen GL, Ketchum NS, Michalek JE, Swaby JA. Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemiology. 1997;8(3):252–258.
    1. Howard BV. Insulin resistance and lipid metabolism. Am J Cardiol. 1999;84(1A):28J–32J.
    1. Jacobs DR, Jr, Hannan PJ, Wallace D, Liu K, Williams OD, Lewis CE. Interpreting age, period and cohort effects in plasma lipids and serum insulin using repeated measures regression analysis: the CARDIA Study. Stat Med. 1999;18(6):655–679.
    1. Lee DH, Jacobs DR, Jr, Porta M. Could low-level background exposure to persistent organic pollutants contribute to the social burden of type 2 diabetes? J Epidemiol Community Health. 2006a;60(12):1006–1008.
    1. Lee DH, Lee IK, Jin SH, Steffes M, Jacobs DR., Jr Association between serum concentrations of persistent organic pollutants and insulin resistance among nondiabetic adults: results from the National Health and Nutrition Examination Survey 1999–2002. Diabetes Care. 2007a;30(3):622–628.
    1. 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. 2007b;50(9):1841–1851.
    1. Lee DH, Lee IK, Song K, Steffes M, Toscano W, Baker BA, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999–2002. Diabetes Care. 2006b;29(7):1638–1644.
    1. Lee DH, Lee IK, Steffes M, Jacobs DR., Jr Extended analyses of the association between serum concentrations of persistent organic pollutants and diabetes. Diabetes Care. 2007c;30(6):1596–1598.
    1. Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002;23(2):201–229.
    1. Li QQ, Loganath A, Chong YS, Tan J, Obbard JP. Persistent organic pollutants and adverse health effects in humans. J Toxicol Environ Health A. 2006;69(21):1987–2005.
    1. Longnecker MP, Michalek JE. Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure. Epidemiology. 2000;11(1):44–48.
    1. Lopez-Carrillo L, Torres-Sanchez L, Lopez-Cervantes M, Blair A, Cebrian ME, Uribe M. The adipose tissue to serum dichlorodiphenyldichloroethane (DDE) ratio: some methodological considerations. Environ Res. 1999;81(2):142–145.
    1. McFarland VA, Clarke JU. Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis. Environ Health Perspect. 1989;81:225–239.
    1. Medlock KL, Lyttle CR, Kelepouris N, Newman ED, Sheehan DM. Estradiol down-regulation of the rat uterine estrogen receptor. Proc Soc Exp Biol Med. 1991;196(3):293–300.
    1. Nebert DW, Puga A, Vasiliou V. Role of the Ah receptor and the dioxin-inducible [Ah] gene battery in toxicity, cancer, and signal transduction. Ann NY Acad Sci. 1993;23:624–640.
    1. Needham LL, Barr DB, Caudill SP, Pirkle JL, Turner WE, Osterloh J, et al. Concentrations of environmental chemicals associated with neurodevelopmental effects in U.S. population. Neurotoxicology. 2005;26(4):531–545.
    1. Phillips KP, Foster WG, Leiss W, Sahni V, Karyakina N, Turner MC, et al. Assessing and managing risks arising from exposure to endocrine-active chemicals. J Toxicol Environ Health B Crit Rev. 2008;11(3–4):351–372.
    1. Schisterman EF, Whitcomb BW, Louis GM, Louis TA. Lipid adjustment in the analysis of environmental contaminants and human health risks. Environ Health Perspect. 2005;113:853–857.
    1. Sjödin A, Jones RS, Lapeza CR, Focant JF, McGahee EE, 3rd, Patterson DG., Jr Semiautomated high-throughput extraction and cleanup method for the measurement of polybrominated diphenyl ethers, polybrominated biphenyls, and polychlorinated biphenyls in human serum. Anal Chem. 2004;76(7):1921–1927.
    1. Steenland K, Piacitelli L, Deddens J, Fingerhut M, Chang LI. Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Natl Cancer Inst. 1999;91(9):779–786.
    1. Thomaseth K, Salvan A. Estimation of occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using a minimal physiologic toxicokinetic model. Environ Health Perspect. 1998;106(suppl 2):743–753.
    1. Turyk M, Anderson H, Knobeloch L, Imm P, Persky V. Organochlorine exposure and incidence of diabetes in a cohort of Great Lakes sport fish consumers. Environ Health Perspect. 2009;117:1076–1082.
    1. Vasseur P, Cossu-Leguille C. Linking molecular interactions to consequent effects of persistent organic pollutants (POPs) upon populations. Chemosphere. 2006;62(7):1033–1042.
    1. Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environ Health Perspect. 2003;111:994–1006.
    1. Wolff MS, Camann D, Gammon M, Stellman SD. Proposed PCB congener groupings for epidemiological studies. Environ Health Perspect. 1997;105:13–14.

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