西部典型地区PM2.5对2型糖尿病发病影响及机制的前瞻性队列研究

With the background of serious air PM2.5 pollution and higher prevalence of type 2 diabetes (T2DM) in China, the relationship between PM2.5 and T2DM has been focused widely. Because the long term monitoring data of PM2.5 in China is lack, limited studies focused on the effect of PM2.5 onT2DM incidence and the biological mechanism. .This research will base on the platform of “Jinchang Cohort”. Firstly, subject-level PM2.5 exposure were created by averaging concentrations for the period 2005-2015 using estimates of PM2.5 derived from satellite remote sensing observations of aerosol optical depth and assigning these values to each subject by their place of residence in baseline data. Secondly, prospective cohort study will be carried out to reveal the health risk of long term exposure to PM2.5 on T2DM incidence among normal and pre-diabetes people. .Thirdly, T2DM new cases in Jinchang Cohort will be selected to research on the biological mechanism. (1) Physical examination data will be used to reveal the association between PM2.5 and the change scope of physiological and biochemical indexes in the onset process of T2DM at the population level, and the related sensitive indexes will be found. (2) The blood sample of some T2DM new cases and controls will be selected from biological samples library of Jinchang Cohort. ELISA methods will be used to test some pancreas islet function biomarker. Then the dose-response relationship between exposure to PM2.5 and these biomarkers change scope in the onset process of T2DM will be discovered at individual level. .In the end, this program will reveal the adverse effect of long term exposure PM2.5 on T2DM incidence, and find the potential biological mechanism in a population-based study , which could provide a scientific basis for deeply assessing the health risk of PM2.5 on T2DM.

随着我国PM2.5污染日趋加重及2型糖尿病（T2DM）患病率快速上升，PM2.5对T2DM影响问题成为新热点。本项目针对我国长序列PM2.5历史数据缺乏及其对T2DM发病风险与机制研究的缺憾，依托甘肃5万人“金昌队列”平台，首先采用卫星遥感技术反演近10年金昌市PM2.5暴露水平，由此开展PM2.5对正常人与糖尿病前期人群发生T2DM风险的前瞻性队列研究，定量评估PM2.5对T2DM发病的风险。进而以队列随访中T2DM新发病例为研究对象，一方面利用体检数据从群体水平构建PM2.5与T2DM发生过程中相关理化指标的暴露-反应关系；另一方面通过实验室生物样本检测从个体水平分析在T2DM发生过程中PM2.5对胰岛功能生物标志物的影响，最终揭示PM2.5暴露对人体T2DM发病的潜在生物学机制，实现以人群为基础的试验研究，弥补以往动物实验的不足，为深入开展PM2.5与T2DM的健康风险评估提供依据。

依托“金昌队列”平台，在我国西部地区开展PM10暴露对2型糖尿病患病、发病及生物机制的影响研究。研究结果显示：1）大气PM10浓度每升高10μg/m3，糖尿病患病风险增加5%（OR=1.05, 95%CI：1.01-1.09），且随着PM10浓度的增加而上升（P-trend=0.016）。2）大气PM10浓度每增加10μg/m3，糖尿病发病率将上升17%（HR=1.17，95%CI：1.08-1.26），且随着大气PM10浓度升高，糖尿病发病风险逐渐升高（P-trend<0.05）。3）横断面研究显示，随着PM10污染物浓度每增加10μg/m3，基线总人群空腹血糖、葡萄糖甘油三酯指数、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白分别增加0.10%、-0.02%、0.05%、-0.40%、0.14%、0.14。 4）前瞻性研究显示，随着基线PM10污染物浓度每增加10μg/m3，人群2年平均随访期间内相关理化指标的升高风险均有不同增加，其HR分别为1.29(95%CI:1.26,1.32)、1.29(95%CI:1.26,1.33)、1.32(95%CI:1.29,1.35)、1.27(95%CI:1.24,1.31)、1.32(95%CI:1.28,1.35)、1.27(95%CI:1.24,1.30)、1.36(95%CI:1.33,1.39)、1.32(95%CI:1.28,1.35)、1.32(95%CI:1.29,1.36)。5）实验室研究显示，随着PM10浓度每升高10μg/m3 ，血糖正常人群VCAM1炎症因子将上升10.85%，胰岛素和胰岛B 细胞功能分别下降2.86%和4.50%。针对糖尿病前期人群，随着PM10浓度每升高10μg/m3，其炎症因子IL6和VCAM1分别上升1.21%和2.22%。对糖尿病患者而言，随着PM10浓度每升高10μg/m3糖尿病患者8-iso-PGF2α水平将增加5.65%。综上所述，大气PM10暴露将导致2型糖尿病的发生风险有所增加，其主要生物学机制是通过影响人群空腹血糖、代谢性指标、炎症反应、氧化损伤及胰岛功能而产生效应。