2型糖尿病是影响发达国家和发展中国家的重要公共卫生问题。有研究认为血浆转甲状腺素蛋白水平增高与2型糖尿病患病风险增加有关，但结论不一致。目前，中国人群中关于血浆转甲状腺素蛋白水平与2型糖尿病的关联性研究较少，且未见前瞻性研究的报道。鉴于此，本研究拟在前期建立的约3000对新诊断2型糖尿病病例对照数据库中探讨血浆转甲状腺素蛋白水平与2型糖尿病患病风险之间的关系，并在已经建立的前瞻性队列中进行验证。通过对转甲状腺素蛋白代谢相关基因位点的筛选和后续测定，挖掘遗传因素对上述关系的修正作用。与此同时，通过慢病毒转染人肝癌HepG2细胞系，验证人群研究中的交互作用结果，并探讨血浆转甲状腺素蛋白是否可以独立于视黄醇结合蛋白在2型糖尿病的发生发展中发挥作用。本项目的实施将有助于完善转甲状腺素蛋白影响2型糖尿病的分子机制，并为2型糖尿病个体化预防和干预提供基础数据。

Type 2 diabetes mellitus (T2DM) is a major public health problem affecting both developed and developing countries. Some studies have suggested that elevated plasma transthyretin (TTR) levels are associated with an increased risk of T2DM, but the conclusions remain inconsistent. So far, there are few studies focused on the relationship between plasma TTR levels and risk of T2DM in Chinese populations, along with no prospective studies being reported. Therefore, the present study will be designed to explore the above relationship in a pre-established 3000 pairs of newly diagnosed T2DM case-control databases and to validate the results in an established prospective cohort. In addition, genetic modifications will also be evaluated through screening and validating of TTR-related gene loci. Moreover, interaction results in population studies, together with whether TTR can play a role in the development of T2DM independent of retinol-binding protein 4 will be investigated by using lentiviral vector-transduced human hepatoma (HepG2) cell lines. The implementation of the present project is not only helpful to complete the molecular mechanisms of TTR affecting T2DM, but also supply important information for individualized T2DM prevention and intervention.