Abstract
Air pollution is known to be a major risk factor for cardiopulmonary disease, but this is unclear for cardiometabolic disease (e.g. diabetes). This is of considerable public health importance, given the nationwide epidemic of diabetes, accompanied by severe air pollution, in China. The evidence so far remained inadequate to answer questions of whether individuals with cardiometabolic dysfunctions are susceptible to air pollution and whether air pollution exacerbates diabetes development via certain biological pathways. In this manuscript, we summarize the results and limitations of studies exploring these two topics and elaborate our design of a prospective panel study (SCOPE) as a solution. We assessed and compared the health effect of air pollution among pre-diabetic individuals and matched healthy controls through four repeated clinical visits over 1 year. Comprehensive evaluation was made to both health endpoints and exposure. The primary biomarkers were assessed to reveal the impact on multiple biological pathways, including glycolipid metabolism and insulin resistance, endothelial function, and inflammation. Detailed chemical and size fractional components of particulate matter were measured in this study, along with the application of personal monitors. The work should increase our understanding of how air pollution affects individuals with cardiometabolic dysfunction and the underlying mechanisms.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Barraza-Villarreal, A., Sunyer, J., Hernandez-Cadena, L., Escamilla-Nuñez, M.C., Sienra-Monge, J.J., Ramírez-Aguilar, M., Cortez-Lugo, M., Holguin, F., Diaz-Sánchez, D., Olin, A.C., and Romieu, I. (2008). Air pollution, airway inflammation, and lung function in a cohort study of mexico city schoolchildren. Environ Health Perspect 116, 832–838.
Bragg, F., Holmes, M.V., Iona, A., Guo, Y., Du, H., Chen, Y., Bian, Z., Yang, L., Herrington, W., Bennett, D., Turnbull, I., Liu, Y., Feng, S., Chen, J., Clarke, R., Collins, R., Peto, R., Li, L., Chen, Z., and Chen, Z. (2017). Association between diabetes and cause-specific mortality in rural and urban areas of China. JAMA 317, 280–289.
Brook, R.D., Rajagopalan, S., Pope, C.A., Brook, J.R., Bhatnagar, A., Diez-Roux, A.V., Holguin, F., Hong, Y., Luepker, R.V., Mittleman, M.A., Peters, A., Siscovick, D., Smith, S.C., Whitsel, L., Kaufman, J.D., and Kaufman, J.D. (2010). Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the american heart association. Circulation 121, 2331–2378.
Brook, R.D., Xu, X., Bard, R.L., Dvonch, J.T., Morishita, M., Kaciroti, N., Sun, Q., Harkema, J., and Rajagopalan, S. (2013). Reduced metabolic insulin sensitivity following sub-acute exposures to low levels of ambient fine particulate matter air pollution. Sci Total Environ 448, 66–71.
Brook, R.D., Sun, Z., Brook, J.R., Zhao, X., Ruan, Y., Yan, J., Mukherjee, B., Rao, X., Duan, F., Sun, L., Liang, R., Lian, H., Zhang, S., Fang, Q., Gu, D., Sun, Q., Fan, Z., and Rajagopalan, S. (2016). Extreme air pollution conditions adversely affect blood pressure and insulin resistancenovelty and significance. Hypertension 67, 77–85.
Calderón-Garcidueñas, L., Cross, J.V., Franco-Lira, M., Aragón-Flores, M., Kavanaugh, M., Torres-Jardón, R., Chao, C., Thompson, C., Chang, J., Zhu, H., and D’Angiulli, A. (2013). Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution. Front Neurosci 7, 183.
Chemla, D., Nitenberg, A., Teboul, J.L., Richard, C., Monnet, X., le Clesiau, H., Valensi, P., and Brahimi, M. (2008). Subendocardial viability ratio estimated by arterial tonometry: a critical evaluation in elderly hypertensive patients with increased aortic stiffness. Clin Exp Pharmacol Physiol 35, 909–915.
Chen, H., Burnett, R.T., Kwong, J.C., Villeneuve, P.J., Goldberg, M.S., Brook, R.D., van Donkelaar, A., Jerrett, M., Martin, R.V., Brook, J.R., and Copes, R. (2013). Risk of incident diabetes in relation to long-term exposure to fine particulate matter in Ontario, Canada. Environ Health Perspect 121, 804–810.
Chuang, K.J., Yan, Y.H., and Cheng, T.J. (2010). Effect of air pollution on blood pressure, blood lipids, and blood sugar: a population-based approach. J Occupat Environ Med 52, 258–262.
Chuang, K.J., Yan, Y.H., Chiu, S.Y., and Cheng, T.J. (2011). Long-term air pollution exposure and risk factors for cardiovascular diseases among the elderly in Taiwan. Occupat Environ Med 68, 64–68.
Coogan, P.F., White, L.F., Jerrett, M., Brook, R.D., Su, J.G., Seto, E., Burnett, R., Palmer, J.R., and Rosenberg, L. (2012). Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles. Circulation 125, 767–772.
Dunn, W.B., Broadhurst, D., Begley, P., Zelena, E., Francis-McIntyre, S., Anderson, N., Brown, M., Knowles, J.D., Halsall, A., Haselden, J.N., Nicholls, A.W., Wilson, I.D., Kell, D.B., Goodacre, R., and Goodacre, R. (2011). Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc 6, 1060–1083.
Gandhi, P., and Rao, G. (2014). The spectral analysis of photoplethysmography to evaluate an independent cardiovascular risk factor. Int J Gen Med 7, 539–547.
Goldberg, M.S., Burnett, R.T., Yale, J.F., Valois, M.F., and Brook, J.R. (2006). Associations between ambient air pollution and daily mortality among persons with diabetes and cardiovascular disease. Environ Res 100, 255–267.
Gong, J., Zhu, T., Kipen, H., Wang, G., Hu, M., Guo, Q., Ohman-Strickland, P., Lu, S.E., Wang, Y., Zhu, P., Rich, D.Q., Huang, W., and Zhang, J. (2014). Comparisons of ultrafine and fine particles in their associations with biomarkers reflecting physiological pathways. Environ Sci Technol 48, 5264–5273.
Guo, S., Hu, M., Zamora, M.L., Peng, J., Shang, D., Zheng, J., Du, Z., Wu, Z., Shao, M., Zeng, L., Molina, M.J., and Zhang, R. (2014). Elucidating severe urban haze formation in China. Proc Natl Acad Sci USA 111, 17373–17378.
Hamburg, N.M., Keyes, M.J., Larson, M.G., Vasan, R.S., Schnabel, R., Pryde, M.M., Mitchell, G.F., Sheffy, J., Vita, J.A., and Benjamin, E.J. (2008). Cross-sectional relations of digital vascular function to cardiovascular risk factors in the framingham heart study. Circulation 117, 2467–2474.
Han, Y., Zhu, T., Guan, T., Zhu, Y., Liu, J., Ji, Y., Gao, S., Wang, F., Lu, H., and Huang, W. (2016). Association between size-segregated particles in ambient air and acute respiratory inflammation. Sci Total Environ 565, 412–419.
Kelishadi, R., Mirghaffari, N., Poursafa, P., and Gidding, S.S. (2009). Lifestyle and environmental factors associated with inflammation, oxidative stress and insulin resistance in children. Atherosclerosis 203, 311–319.
Kim, J.H., and Hong, Y.C. (2012). GSTM1, GSTT1, and GSTP1 polymorphisms and associations between air pollutants and markers of insulin resistance in elderly koreans. Environ Health Perspect 120, 1378–1384.
Krämer, U., Herder, C., Sugiri, D., Strassburger, K., Schikowski, T., Ranft, U., and Rathmann, W. (2010). Traffic-related air pollution and incident type 2 diabetes: results from the SALIA cohort study. Environ Health Perspect 118, 1273–1279.
Li, R., Qiu, X., Xu, F., Lin, Y., Fang, Y., and Zhu, T. (2016). Macrophagemediated effects of airborne fine particulate matter (PM2.5) on hepatocyte insulin resistance in vitro. ACS Omega 1, 736–743.
Lin, W., Huang, W., Zhu, T., Hu, M., Brunekreef, B., Zhang, Y., Liu, X., Cheng, H., Gehring, U., Li, C., and Tang, X. (2011). Acute respiratory inflammation in children and black carbon in ambient air before and during the 2008 Beijing Olympics. Environ Health Perspect 119, 1507–1512.
Lin, W., Zhu, T., Xue, T., Peng, W., Brunekreef, B., Gehring, U., Huang, W., Hu, M., Zhang, Y., and Tang, X. (2015). association between changes in exposure to air pollution and biomarkers of oxidative stress in children before and during the Beijing Olympics. Am J Epidemiol 181, 575–583.
Lin, Y., Ma, Y., Qiu, X., Li, R., Fang, Y., Wang, J., Zhu, Y., and Hu, D. (2015). Sources, transformation, and health implications of PAHs and their nitrated, hydroxylated, and oxygenated derivatives in PM2.5 in Beijing. J Geophys Res Atmos 120, 7219–7228.
Liu, J., Han, Y., Tang, X., Zhu, J., and Zhu, T. (2016). Estimating adult mortality attributable to PM2.5 exposure in China with assimilated PM2.5 concentrations based on a ground monitoring network. Sci Total Environ 568, 1253–1262.
Mo, Y., Wan, R., Wang, J., Chien, S., Tollerud, D.J., and Zhang, Q. (2009). Diabetes is associated with increased sensitivity of alveolar macrophages to urban particulate matter exposure. Toxicology 262, 130–137.
O’Neill, M.S., Veves, A., Zanobetti, A., Sarnat, J.A., Gold, D.R., Economides, P.A., Horton, E.S., and Schwartz, J. (2005). Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function. Circulation 111, 2913–2920.
O’Neill, M.S., Veves, A., Sarnat, J.A., Zanobetti, A., Gold, D.R., Economides, P.A., Horton, E.S., and Schwartz, J. (2006). Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility. Occupat Environ Med 64, 373–379.
Oberdörster, G., Oberdörster, E., and Oberdörster, J. (2005). Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113, 823–839.
Ouyang, Y., Virasch, N., Hao, P., Aubrey, M.T., Mukerjee, N., Bierer, B.E., and Freed, B.M. (2000). Suppression of human IL-1β, IL-2, IFN-γ, and TNF-α production by cigarette smoke extracts. J Allergy Clin Immunol 106, 280–287.
Pearson, J.F., Bachireddy, C., Shyamprasad, S., Goldfine, A.B., and Brownstein, J.S. (2010). Association between fine particulate matter and diabetes prevalence in the U.S.. Diabetes Care 33, 2196–2201.
Rich, D.Q., Kipen, H.M., Huang, W., Wang, G., Wang, Y., Zhu, P., Ohman-Strickland, P., Hu, M., Philipp, C., Diehl, S.R., Lu, S.E., Tong, J., Gong, J., Thomas, D., Zhu, T., and Zhang, J.J. (2012). Association between changes in air pollution levels during the beijing olympics and biomarkers of inflammation and thrombosis in healthy young adults. JAMA 307, 2068–2078.
Rignell-Hydbom, A., Lidfeldt, J., Kiviranta, H., Rantakokko, P., Samsioe, G., Agardh, C.D., and Rylander, L. (2009). Exposure to p,p′-DDE: a risk factor for type 2 diabetes. PLoS ONE 4, e7503.
Schneider, A., Neas, L., Herbst, M.C., Case, M., Williams, R.W., Cascio, W., Hinderliter, A., Holguin, F., Buse, J.B., Dungan, K., Styner, M., Peters, A., and Devlin, R.B. (2008). Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals. Environ Health Perspect 116, 1666–1674.
Sun, Q., Wang, A., Jin, X., Natanzon, A., Duquaine, D., Brook, R.D., Aguinaldo, J.G.S., Fayad, Z.A., Fuster, V., Lippmann, M., Chen, L.C., and Rajagopalan, S. (2005). Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA 294, 3003–3010.
Sun, Y., Song, X., Han, Y., Ji, Y., Gao, S., Shang, Y., Lu, S., Zhu, T., and Huang, W. (2015). Size-fractioned ultrafine particles and black carbon associated with autonomic dysfunction in subjects with diabetes or impaired glucose tolerance in Shanghai, China. Part Fibre Toxicol 12, 8.
Sun, Z., Mukherjee, B., Brook, R.D., Gatts, G.A., Yang, F., Sun, Q., Brook, J.R., Fan, Z., and Rajagopalan, S. (2013). Air-Pollution and Cardiometabolic Diseases (AIRCMD): a prospective study investigating the impact of air pollution exposure and propensity for type II diabetes. Sci Total Environ 448, 72–78.
Suzuki, H., Sasaki, T., Kumagai, T., Sakaguchi, S., and Nagata, K. (2010). Malondialdehyde-modified low density lipoprotein (MDA-LDL)-induced cell growth was suppressed by polycyclic aromatic hydrocarbons (PAHs). J Toxicol Sci 35, 137–147.
Vaughan, J., Ngamtrakulpanit, L., Pajewski, T.N., Turner, R., Nguyen, T.A., Smith, A., Urban, P., Hom, S., Gaston, B., and Hunt, J. (2003). Exhaled breath condensate pH is a robust and reproducible assay of airway acidity. Eur Respir J 22, 889–894.
Weber, T., Auer, J., O’Rourke, M.F., Kvas, E., Lassnig, E., Berent, R., and Eber, B. (2004). Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation 109, 184–189.
Wu, L.L., Chiou, C.C., Chang, P.Y., and Wu, J.T. (2004). Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clinica Chim Acta 339, 1–9.
Xu, Y., Wang, L., He, J., Bi, Y., Li, M., Wang, T., Wang, L., Jiang, Y., Dai, M., Lu, J., Xu, M., Li, Y., Hu, N., Li, J., Mi, S., Chen, C.S., Li, G., Mu, Y., Zhao, J., Kong, L., Chen, J., Lai, S., Wang, W., Zhao, W., Ning, G., and Ning, G. (2013). Prevalence and control of diabetes in chinese adults. JAMA 310, 948–958.
Yang, G., Wang, Y., Zeng, Y., Gao, G.F., Liang, X., Zhou, M., Wan, X., Yu, S., Jiang, Y., Naghavi, M., Vos, T., Wang, H., Lopez, A.D., and Murray, C.J. (2013). Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 381, 1987–2015.
Yeatts, K., Svendsen, E., Creason, J., Alexis, N., Herbst, M., Scott, J., Kupper, L., Williams, R., Neas, L., Cascio, W., Devlin, R.B., and Peden, D.B. (2007). Coarse Particulate Matter (PM2.5–10) affects heart rate variability, blood lipids, and circulating eosinophils in adults with asthma. Environ Health Perspect 115, 709–714.
Yin, P., Lehmann, R., and Xu, G. (2015). Effects of pre-analytical processes on blood samples used in metabolomics studies. Anal Bioanal Chem 407, 4879–4892.
Zanobetti, A., and Schwartz, J. (2002). Cardiovascular damage by airborne particles: are diabetics more susceptible? Epidemiology 13, 588–592.
Zhao, X., Sun, Z., Ruan, Y., Yan, J., Mukherjee, B., Yang, F., Duan, F., Sun, L., Liang, R., Lian, H., Zhang, S., Fang, Q., Gu, D., Brook, J.R., Sun, Q., Brook, R.D., Rajagopalan, S., and Fan, Z. (2014). Personal black carbon exposure influences ambulatory blood pressurenovelty and significance. Hypertension 63, 871–877.
Acknowledgements
We are greatly thankful to all the volunteers from our group and PKU hospital who helped to accomplish the study. This work was supported by the National Natural Science Foundation of China (41421064, 21190051, 41121004), and the China Postdoc Science Foundation (154248).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Figure S1
Step by step screening strategy.
Figure S2 Description of subjects residential location.
Table S1 Community clustering condition
Rights and permissions
About this article
Cite this article
Wang, Y., Han, Y., Zhu, T. et al. A prospective study (SCOPE) comparing the cardiometabolic and respiratory effects of air pollution exposure on healthy and pre-diabetic individuals. Sci. China Life Sci. 61, 46–56 (2018). https://doi.org/10.1007/s11427-017-9074-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-017-9074-2