Identification and apportionment of source-specific contributions to the PM2.5-induced effects on type 2 diabetes in Hong Kong

Type 2 diabetes mellitus (T2DM), characterized by insulin resistant (IR), is a quickly growing global disease. In Hong Kong, diabetes is a major cause of morbidity and mortality, and it ranked the tenth leading disease of death in 2013. Recent epidemiological and experimental studies have demonstrated a positive association between exposure to PM2.5 and the development of T2DM. However, our understanding on the mechanisms underlying such an association and the source-specific contributions of PM2.5 to the induced susceptibility to T2DM is still quite limited. To investigate the PM2.5-induced toxicological effects, five T2DM-related biological factors including three pro-inflammation cytokines (IL-6, IL-1β and TNF-α), one key player for insulin resistant (insulin receptor substrate 1, IRS-1) and reactive oxygen species (ROS) activity will be measured. We plan to expose human lung epithelia cell (A549) to 61 PM2.5 samples collected in Hong Kong during a one-year long period, and measure the pro-inflammatory response in lung cells. Phosphorylation of IRS-1 on serine-307 activated by PM2.5-induced pro-inflammation cytokines will be determined using human hepatic cell line (LO-2). Chemical components of PM2.5 including metals, ionic species, elemental carbon, organic carbon, and organic species, especially PAHs and their nitrated-, oxygenated-, and hydroxylated derivatives and organic markers of various primary and secondary sources, will be identified and quantified using a series of advanced analytical techniques. Using the measured biological and chemical data, both positive matrix factorization and multivariate linear regression model will be applied to identify and apportion the contributions of major PM2.5 sources to oxidative stress, pro-inflammatory effects, and IR induced by PM2.5 exposure. The seasonal variability of the source-specific contributions to PM2.5-induced effects on T2DM and other toxicological responses, and the influences of origin of air masses, aerosol acidity, and major gaseous oxidants on these source-specific contributions will be assessed. Moreover, by investigating the correlations of measured toxicological responses with individual chemical species or specific groups of compounds (e.g. PAHs), the key “toxic” species/groups of compounds that are responsible for the PM2.5-induced effects on T2DM will be identified. Such a comprehensive study on the source-specific contributions of PM2.5 to the induced susceptibility to T2DM has not been carried out in the region before. Results from this project will provide scientific basis for the prediction of PM-associated adverse health effects and help the policy makers to formulate cost-effective and targeted PM mitigation strategies and diabetes control policies that may provide significant public health benefits.