申请者致力于糖尿病及心血管并发症的早期筛查及危险因素研究。在参与建立学科三大研究队列基础上，首次采用国际最新诊断标准，系统阐述我国成人糖尿病患病和控制现状；率先引入“心血管健康”概念，全面剖析我国成人心血管健康行为和健康因素达标情况，为国家制定慢病防控策略提供科学依据。长期关注糖尿病相关血清生物标志物，并进一步聚焦血清肝脏因子与代谢紊乱相关研究领域，率先在队列人群中探讨肝脏因子Fetuin-A与糖尿病的相关性，并初步发现全新血清肝脏因子GREM2可能参与调节血糖代谢。以第一或通讯作者在JAMA，JACC，Diabetes Care等期刊发表SCI收录论文15篇，第一或通讯作者论文总影响因子105.5分，单篇最高他引289次。本项目拟延续前期工作，结合人群队列和动物模型深入探讨GREM2在改善胰岛素抵抗参与血糖代谢中的作用及分子机制，最终发现可以运用于临床的疾病预测标志物及药物干预靶点。

The applicant has committed herself to the research of early diagnosis and risk factors of diabetes and cardiovascular complications. Based on 3 large national cohorts, the applicant and her research team reported current prevalence and control rates of diabetes in Chinese adults using the most updated diagnostic criteria. She is among the first to integrate the concept of 'cardiovascular health' and reported the status of cardiovascular health behaviors and health factors in the general population of China. This has provided invaluable data for the country to plan strategically for chronic disease prevention and treatment. The applicant has focused her research on serum biomarkers of diabetes and hepatokines in particular. She found that Fetuin-A, one of the hepatokines, is associated with risks of diabetes, metabolic syndrome, insulin resistance, and albuminuria. In addition, she and her research team have identified a novel hepatokine GREM2, which might play an important role in the regulation of insulin sensitivity and glucose metabolism according to their preliminary data. She has published 15 first- or corresponding-authored original research papers in journals such as JAMA, JACC, and Diabetes Care. The overall impact factor for her first- and corresponding-authored papers is 105.5 and the highest singer-paper citation is 289 times. The proposed project aims (1) to explore further the association and potential causal relationship between GREM2 and insulin sensitivity using population cohorts and animal models; (2) to examine the molecular mechanisms of GREM2-BMP-SMAD/P38MAPK signaling pathway in the regulation of glucose metabolism. Pursuit of this study will facilitate the discovery of new biomarkers for diabetes prediction and new targets for diabetes treatment.