既往研究报道肠黏膜上皮细胞损伤的标志物与糖尿病密切相关，而且在动物实验中发现肠黏膜上皮细胞损伤引起的肠道细菌易位是参与糖尿病发病的重要机制。血清16S rDNA主要是肠道细菌易位至外周血后降解产生。但是，迄今为止血清16S rDNA与糖尿病的关联性尚无可靠的人群证据。缺乏敏感性高、特异性好的定量检测方法是阻碍研究的重要原因之一。我们拟通过建立基于Real-time PCR的血清16S rDNA定量检测方法，结合已有的大队列研究人群基础（已具有18550例对象的基线资料和血清标本），采用巢式病例对照研究方法，针对新发生的糖尿病病例和相应的对照，进行基线16S rDNA的检测，分析并明确血清16S rDNA与糖尿病的关联性、16S rDNA与其他传统危险因素的交互作用对糖尿病发病的影响。本研究将为糖尿病的病因研究和防控研究提供新的思路。

In the previous studies, significant associations were observed between the markers of enterocyte damage and diabetes mellitus (DM). Moreover, the gut bacteria translocation caused by enterocyte damage was proved as a critical factor involved in DM development in animal experiments. Serum 16S rDNA, mainly produced by bacteria in peripheral blood, is widely used as an indicator for bacteria translocation in previous studies. However, the population evidences for the associations between serum 16S rDNA and DM remain insufficient so far. A lack of quantitative measurement method with higher sensitivity and better specificity for the serum 16S rDNA detection is an important reason that stands in the way of the further research. In order to analyze the relationships between serum 16S rDNA and DM in population in the present study, firstly, we will develop the new real-time PCR for the serum 16S rDNA quantitative measurement. Secondly, we will conduct the nested case-control study based on the large cohort study established before (including 18550 subjects with detailed baseline information and serum samples). Thirdly, the DM patients and controls will be selected in the follow-up study according to the exclusion and inclusion criteria. The 16S rDNA levels in baseline serum samples will be quantified in all of selected subjects. Lastly, we will analyze the associations between the serum 16S rDNA and DM, and the effects of the interaction between 16S rDNA and traditional DM risk factors on the DM development. Our study will provide the new strategies for the research on the pathogeny and prevention of diabetes.