环境双酚A与夜间轮班作业在Ⅱ型糖尿病发病中的交互作用及机制研究

Understanding interactions amongst different exposures on the etiology of type II diabetes mellitus (T2DM) has important implications for public health. Limited evidence shown that Bisphenol A (BPA) and night shift work are the independent risk factors for the development of T2DM; however, their interactive effects on the etiology of T2DM remains unclear. The NSFC provides us one-year funding (no. 81273172) which helps us to establish a prospective cohort of 6000 workers with night shift work and 6000 workers without night shift work by the end of 2013. Up to the early March of 2013, we have recruited more than 1000 workers, and it is promising that we can be able to recruit an overall of 12000 cohort members at the baseline. In this proposed project, we shall make use of this existing cohort by further collection of workers' urine samples. By measuring the urinary BPA level in the baseline and in the subsequent 3 years of follow-up, we primarily intend to examine the dose-response relationship between BPA exposure and the risk of T2DM (primary outcome), and secondarily to examine the association with the risk of prediabeties - HbA1C, fasting plasma glucose or impaired glucose tolerance. In addition, the additive and multiplicative interaction between BPA exposure and night shift work for the risk of T2DM will also be examined. Meanwhile, we will measure the plasma concentration of inflammatory cytokines including IL-1b, TNFa, IL-6, adiponectin, and white cell count. The associations of different types of inflammatory cytokines with BPA exposure and night shift work will be studied, and the biological mechanisms for T2DM will also be better understood. Results from this proposed study shall be able to contribute solid evidence to the current literature regarding the associations amongst BPA exposure, night shift work, and the risk of T2DM development.

证据显示双酚A（BPA）与夜间轮班作业分别是Ⅱ型糖尿病（T2DM）独立的环境或职业危险因素，二者联合暴露在人群中广泛存在，但对T2DM发病的交互作用并不清楚。我们在研的1年期NSFC项目旨在建立包括6000名夜间轮班作业工人和6000名非暴露工人的队列基线，以观察夜间轮班作业与将来代谢综合征发生的关联性，以此为基础，本课题计划将基线人群随访3年，并增加BPA暴露评价，测量基线及随访期间尿液BPA浓度，以T2DM及T2DM前期病变（糖化血红蛋白升高、空腹血糖升高或糖耐量异常）为一级和二级观察终点，分析环境BPA暴露对T2DM发病的独立效应及与夜间轮班作业之间相乘或相加的联合效应，检测血液中IL-1β、TNFα、IL-6、脂联素、白细胞计数等炎性指标，探讨炎性因子与单一或联合暴露的关系以及对T2DM发病的预测价值，本课题为确立环境BPA与夜间轮班作业联合暴露与T2DM的关联性提供新的证据。

夜间轮班工作广泛存在于零售、交通运输、卫生服务等各种行业。现有证据表明夜间轮班工作增加糖尿病、代谢综合征、脂肪肝和肥胖等代谢相关疾病的发病风险，但具体机制并不清楚。本课题建立6889人的夜间轮班工人前瞻性队列，其中近一半从事夜间轮班工作；详细评估他们的夜班工作暴露以及其他相关危险因素；每年随访工人一次，鉴定糖尿病、代谢综合征和其他代谢相关疾病的新发病例，以确定夜间轮班工作在这些疾病发病中的作用和可能的机制。.基于目前的数据分析结果显示，夜间轮班工作与超重/肥胖的发生有关，增加20%的腹型肥胖发生风险。与其他类型的夜间轮班工作相比，常夜班工人的腹型肥胖发生风险最高，增加2.34倍。职业人群体检中肝酶ALT和AST异常发生率较高，其原因并不十分清楚。夜间轮班工作能引起脂肪肝，而脂肪肝与与肝酶异常有密切联系。一般认为脂肪肝可能在夜间轮班工作引起的肝酶异常中发挥中介作用。但是我们的研究结果表明，非脂肪肝工人从事夜班工作发生血清ALT水平异常的风险升高，而且随着从事夜班工作时间的增加，风险不断提高。结果提示脂肪肝在夜间轮班工作相关的ALT异常中并无中介作用，其具体机制需要深入研究。工人双酚A暴露和炎性因子测定仍在进行中，研究结果将陆续发表。

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