Polycyclic aromatic hydrocarbons (PAHs) are formed
due to natural and anthropogenic activities and known for their
potential impact and persistence in the environment. PAHs exposure has been
linked to cause adverse health effect including lung cancer, heart conditions
and genetic mutations. The understanding of metabolic effects of PAHs exposure is less clear especially in the presence of
pro-inflammatory stress like alcoholism or diabetes.The aim of this article is to understand the metabolic effects
of PAHs exposure on Type 2 Diabetes Mellitus (T2DM) by analyzing the clinical
biomarkers data retrieved from the National Health and Nutrition Examination
Survey, Center for Disease Control (CDC NHANES) (2015-16). This study has also
accessed the interactive impact of PAHs and other proinflammatory factors, like
alcohol intake on the metabolic syndrome on T2DM. We investigated urinary
levels of hydroxylated PAHs metabolites (OH-PAHs) along with demographic,
clinical and laboratory data. Generalize linear model Univariate factorial
ANOVA was used to evaluate the group differences in the demographics, PAH
exposure, drinking patterns, clinical data, and biomarker levels. Linear
regression model was used to analyze the association of biomarkers, PAH
exposure and drinking data. Multivariable regression model was used for
multi-independent model to assess comorbidity association and their effect
sizes on the clinical outcomes. The results indicated that BMI (p = 0.002), and
age (≤0.001) are independent demographic risk factors for T2DM in high PAHs
exposure. Acute proinflammatory activity characterized by CRP, is augmented by
elevated monocyte levels (p ≤ 0.001) and stepwise addition of 1-Hydroxynapthelene
(p = 0.005), and 2-Hydroxynapthelene (p = 0.001) independently. Prevalence of
highest average drinks over time is observed in the high PAHs exposure; with
males drinking almost twice compared to females in highly exposed population.
Pathway response of T2DM shows sexual dimorphism; with males showing
association with triglycerides (p ≤ 0.001), and females with CRP (p = 0.015)
independently with HbA1C.
References
[1]
Department of Health and Human Services PHS (1995) Toxicological Profile for Polycyclic Aromatic Hydrocarbons (PAHs). https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=122&tid=25
[2]
European Commission Scientific Committee on Food (2002) Polycyclic Aromatic Hydrocarbons-Occurrence in Foods, Dietary Exposure, and Health Effects. https://ec.europa.eu/food/system/files/2020-12/sci-com_scf_out154_en.pdf
[3]
Maliszewska-Kordybach, B. (1999) Sources, Concentrations, Fate and Effects of Polycyclic Aromatic Hydrocarbons (PAHs) in the Environment. Part A: PAHs in Air Polish Journal of Environmental Studies, 8, 131-136.
[4]
Li, Z., Wang, Y., Guo, S., Li, Z., Xing, Y., Liu, G., et al. (2019) PM2.5 Associated PAHs and Inorganic Elements from Combustion of Biomass, Cable Wrapping, Domestic Waste, and Garbage for Power Generation. Aerosol and Air Quality Research, 19, 2502-2517. https://doi.org/10.4209/aaqr.2019.10.0495
[5]
Bentsen, R.K., Halgard, K., Noto, H., Daae, H.L. and Ovrebo, S. (1998) Correlation between Urinary 1-Hydroxypyrene and Ambient Air Pyrene Measured with an Inhalable Aerosol Sampler and a Total Dust Sampler in an Electrode Paste Plant. Science of the Total Environment, 212, 59-67. https://doi.org/10.1016/S0048-9697(97)00331-8
[6]
Drukteinis, J.S., Medrano, T., Ablordeppey, E.A., Kitzman, J.M. and Shiverick, K.T. (2005) Benzo[a]pyrene, But Not 2,3,7,8-TCDD, Induces G2/M Cell Cycle Arrest, p21CIP1 and p53 Phosphorylation in Human Choriocarcinoma JEG-3 Cells: A Distinct Signaling Pathway. Placenta, 26, S87-S95. https://doi.org/10.1016/j.placenta.2005.01.013
[7]
Tithof, P.K., Elgayyar, M., Cho, Y., Guan, W., Fisher, A.B. and Peters-Golden, M. (2002) Polycyclic Aromatic Hydrocarbons Present in Cigarette Smoke Cause Endothelial Cell Apoptosis by a Phospholipase A2-Dependent Mechanism. The FASEB Journal, 16, 1463-1464. https://doi.org/10.1096/fj.02-0092fje
[8]
Farhadian, A., Jinap, S., Hanifah, H. and Zaidul, I. (2011) Effects of Meat Preheating and Wrapping on the Levels of Polycyclic Aromatic Hydrocarbons in Charcoal-Grilled Meat. Food Chemistry, 124, 141-146. https://doi.org/10.1016/j.foodchem.2010.05.116
[9]
Singh, L., Varshney, J.G. and Agarwal, T. (2016) Polycyclic Aromatic Hydrocarbons Formation and Occurrence in Processed Food. Food Chemistry, 199, 768. https://doi.org/10.1016/j.foodchem.2015.12.074
[10]
ASTDR (2013) What Are the Standards and Regulations for PAHs Exposure? ASTDR, Environmental Health and Medicine Education. https://www.atsdr.cdc.gov/csem/polycyclic-aromatic-hydrocarbons/standards_and_regulations_for_exposure.html
[11]
Wang, Y., Meng, L., Pittman, E.N., Etheredge, A., Hubbard, K., Trinidad, D.A., et al. (2017) Quantification of Urinary Mono-Hydroxylated Metabolites of Polycyclic Aromatic Hydrocarbons by On-Line Solid Phase Extraction-High Performance Liquid Chromatography-Tandem Mass Spectrometry. Analytical and Bioanalytical Chemistry, 409, 931-937. https://doi.org/10.1007/s00216-016-9933-x
[12]
Jongeneelen, F.J. (2001) Benchmark Guideline for Urinary 1-hydroxypyrene as Biomarker of Occupational Exposure to Polycyclic Aromatic Hydrocarbons. Annals of Occupational Hygiene, 45, 3-13. https://doi.org/10.1016/S0003-4878(00)00009-0
[13]
Nemmar, A. (2004) Possible Mechanisms of the Cardiovascular Effects of Inhaled Particles: Systemic Translocation and Prothrombotic Effects. Toxicology Letters, 149, 243-253. https://doi.org/10.1016/j.toxlet.2003.12.061
[14]
Moorthy, B., Chu, C. and Carlin, D.J. (2015) Polycyclic Aromatic Hydrocarbons: From Metabolism to Lung Cancer. Toxicological Sciences, 145, 5-15. https://doi.org/10.1093/toxsci/kfv040
[15]
Marris, C.R., Kompella, S.N., Miller, M.R., Incardona, J.P., Brette, F., Hancox, J.C., et al. (2020) Polyaromatic Hydrocarbons in Pollution: A Heart-Breaking Matter. The Journal of Physiology, 598, 227-247. https://doi.org/10.1113/JP278885
[16]
Ranjbar, M., Rotondi, M.A., Ardern, C.I. and Kuk, J.L. (2015) Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons Are Associated with Cardiometabolic Health Risk. PLoS ONE, 10, e0137536. https://doi.org/10.1371/journal.pone.0137536
[17]
Penn, A. and Snyder, C. (1988) Arteriosclerotic Plaque Development Is “Promoted” by Polynuclear Aromatic Hydrocarbons. Carcinogenesis, 9, 2185-2189. https://doi.org/10.1093/carcin/9.12.2185
[18]
Sarma, S.N., Kimpe, L.E., Doyon, V.C., Blais, J.M. and Chan, H.M. (2019) A Metabolomics Study on Effects of Polyaromatic Compounds in Oil Sand Extracts on the Respiratory, Hepatic and Nervous Systems Using Three Human Cell Lines. Environmental Research, 178, Article ID: 108680. https://doi.org/10.1016/j.envres.2019.108680
[19]
Curtis, L.R., Garzon, C.B., Arkoosh, M., Collier, T., Myers, M.S., Buzitis, J., et al. (2011) Reduced Cytochrome P4501A Activity and Recovery from Oxidative Stress during Subchronic Benzo[a]pyrene and Benzo[e]pyrene Treatment of Rainbow Trout. Toxicology and Applied Pharmacology, 254, 1-7. https://doi.org/10.1016/j.taap.2011.04.015
[20]
Ataria, J.M., O’Halloran, K. and Gooneratne, R. (2007) Hepatic and Immune Biological Effect Assays in C57BL/6 Mice to Measure Polycyclic Aromatic Hydrocarbon Bioavailability under Laboratory Exposures with Increasing Environmental Relevance. Environmental Science and Pollution Research—International, 14, 256-265. https://doi.org/10.1065/espr2006.04.301
[21]
Ramesh, A., Hood, D.B., Inyang, F., Greenwood, M., Nyanda, A.M., Archibong, A.E., et al. (2002) Comparative Metabolism, Bioavailability, and Toxicokinetics of Benzo[a]pyrene in Rats after Acute Oral, Inhalation, and Intravenous Administration. Polycyclic Aromatic Compounds, 22, 969-980. https://doi.org/10.1080/10406630290104121
[22]
Meigs, J.B. (2000) Invited Commentary: Insulin Resistance Syndrome? Syndrome X? Multiple Metabolic Syndrome? A Syndrome at All? Factor Analysis Reveals Patterns in the Fabric of Correlated Metabolic Risk Factors. American Journal of Epidemiology, 152, 908-911. https://doi.org/10.1093/aje/152.10.908
[23]
Ford, E.S., Li, C. and Sattar, N. (2008) Metabolic Syndrome and Incident Diabetes: Current State of the Evidence. Diabetes Care, 31, 1898-1904. https://doi.org/10.2337/dc08-0423
[24]
Alshaarawy, O., Zhu, M., Ducatman, A.M., Conway, B. and Andrew, M.E. (2014) Urinary Polycyclic Aromatic Hydrocarbon Biomarkers and Diabetes Mellitus. Occupational and Environmental Medicine, 71, 437-441. https://doi.org/10.1136/oemed-2013-101987
[25]
Lee, I., Park, H., Kim, M.J., Kim, S., Choi, S., Park, J., et al. (2022) Exposure to Polycyclic Aromatic Hydrocarbons and Volatile Organic Compounds Is Associated with a Risk of Obesity and Diabetes Mellitus among Korean Adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017. International Journal of Hygiene and Environmental Health, 240, Article ID: 113886. https://doi.org/10.1016/j.ijheh.2021.113886
[26]
Yang, L., Zhou, Y., Sun, H., Lai, H., Liu, C., Yan, K., et al. (2014) Dose-Response Relationship between Polycyclic Aromatic Hydrocarbon Metabolites and Risk of Diabetes in the General Chinese Population. Environmental Pollution, 195, 24-30. https://doi.org/10.1016/j.envpol.2014.08.012
[27]
Yang, L., Yan, K., Zeng, D., Lai, X., Chen, X., Fang, Q., et al. (2017) Association of Polycyclic Aromatic Hydrocarbons Metabolites and Risk of Diabetes in Coke Oven Workers. Environmental Pollution, 223, 305-310. https://doi.org/10.1016/j.envpol.2017.01.027
[28]
Li, K., Yin, R., Wang, Y. and Zhao, D. (2021) Associations between Exposure to Polycyclic Aromatic Hydrocarbons and Metabolic Syndrome in U.S. Adolescents: Cross-Sectional Results from the National Health and Nutrition Examination Survey (2003-2016) Data. Environmental Research, 202, Article ID: 111747. https://doi.org/10.1016/j.envres.2021.111747
[29]
Stallings-Smith, S., Mease, A., Johnson, T.M. and Arikawa, A.Y. (2018) Exploring the Association between Polycyclic Aromatic Hydrocarbons and Diabetes among Adults in the United States. Environmental Research, 166, 588-594. https://doi.org/10.1016/j.envres.2018.06.041
[30]
Sarigiannis, D.Α., Karakitsios, S.P., Zikopoulos, D., Nikolaki, S. and Kermenidou, M. (2015) Lung Cancer Risk from PAHs Emitted from Biomass Combustion. Environmental Research, 137, 147-156. https://doi.org/10.1016/j.envres.2014.12.009
[31]
Armstrong, B.G. and Gibbs, G. (2009) Exposure-Response Relationship between Lung Cancer and Polycyclic Aromatic Hydrocarbons (PAHs). Occupational and Environmental Medicine, 66, 740-746. https://doi.org/10.1136/oem.2008.043711
[32]
Zhang, H., Han, Y., Qiu, X., Wang, Y., Li, W., Liu, J., et al. (2020) Association of Internal Exposure to Polycyclic Aromatic Hydrocarbons with Inflammation and Oxidative Stress in Prediabetic and Healthy Individuals. Chemosphere, 253, Article ID: 126748. https://doi.org/10.1016/j.chemosphere.2020.126748
[33]
Hou, J., Sun, H., Huang, X., Zhou, Y., Zhang, Y., Yin, W., et al. (2017) Exposure to Polycyclic Aromatic Hydrocarbons and Central Obesity Enhanced Risk for Diabetes among Individuals with Poor Lung Function. Chemosphere, 185, 1136-1143. https://doi.org/10.1016/j.chemosphere.2017.07.056
[34]
Alshaarawy, O., Zhu, M., Ducatman, A., Conway, B. and Andrew, M.E. (2013) Polycyclic Aromatic Hydrocarbon Biomarkers and Serum Markers of Inflammation. A Positive Association That Is More Evident in Men. Environmental Research, 126, 98-104. https://doi.org/10.1016/j.envres.2013.07.006
[35]
Farzan, S.F., Chen, Y., Trachtman, H. and Trasande, L. (2016) Urinary Polycyclic Aromatic Hydrocarbons and Measures of Oxidative Stress, Inflammation and Renal Function in Adolescents: NHANES 2003-2008. Environmental Research, 144, 149-157. https://doi.org/10.1016/j.envres.2015.11.012
[36]
Ferguson, K.K., McElrath, T.F., Pace, G.G., Weller, D., Zeng, L., Pennathur, S., et al. (2017) Urinary Polycyclic Aromatic Hydrocarbon Metabolite Associations with Biomarkers of Inflammation, Angiogenesis, and Oxidative Stress in Pregnant Women. Environmental Science & Technology, 51, 4652-4660. https://doi.org/10.1021/acs.est.7b01252
[37]
Rehm, J., Greenfield, T.K. and Rogers, J.D. (2001) Average Volume of Alcohol Consumption, Patterns of Drinking, and All-Cause Mortality: Results from the US National Alcohol Survey. American Journal of Epidemiology, 153, 64-71. https://doi.org/10.1093/aje/153.1.64
[38]
Li, F., Xiang, B., Jin, Y., Li, C., Ren, S., Wu, Y., et al. (2020) Hepatotoxic Effects of Inhalation Exposure to Polycyclic Aromatic Hydrocarbons on Lipid Metabolism of C57BL/6 Mice. Environment International, 134, Article ID: 105000. https://doi.org/10.1016/j.envint.2019.105000
[39]
Tutuncu, Y., Satman, I., Celik, S., Dinccag, N., Karsidag, K., Telci, A., et al. (2016) A Comparison of hs-CRP Levels in New Diabetes Groups Diagnosed Based on FPG, 2-hPG, or HbA1c Criteria. Journal of Diabetes Research, 2016, Article ID: 5827041. https://doi.org/10.1155/2016/5827041
[40]
Zaidi, S.M.H., Ghafoor, A. and Randhawa, F.A. (2015) HbA1c as an Indirect Marker of Hypertriglyceridemia in Type 2 Diabetes Mellitus. Journal of Ayub Medical College Abbottabad, 27, 601-603.
[41]
Shanahan, L., Freeman, J. and Bauldry, S. (2014) Is Very High C-Reactive Protein in Young Adults Associated with Indicators of Chronic Disease Risk? Psychoneuroendocrinology, 40, 76-85. https://doi.org/10.1016/j.psyneuen.2013.10.019
[42]
Khosravipour, M. and Khosravipour, H. (2020) The Association between Urinary Metabolites of Polycyclic Aromatic Hydrocarbons and Diabetes: A Systematic Review and Meta-Analysis Study. Chemosphere, 247, Article ID: 125680. https://doi.org/10.1016/j.chemosphere.2019.125680
[43]
Mumtaz, M., George, J., Gold, K., Cibulas, W. and DeRosa, C. (1996) ATSDR Evaluation of Health Effects of Chemicals. IV. Polycyclic Aromatic Hydrocarbons (PAHs): Understanding a Complex Problem. Toxicology and Industrial Health, 12, 742-971. https://doi.org/10.1177/074823379601200601
[44]
Haffner, S.M. (2006) The Metabolic Syndrome: Inflammation, Diabetes Mellitus, and Cardiovascular Disease. The American Journal of Cardiology, 97, 3-11. https://doi.org/10.1016/j.amjcard.2005.11.010
