中国人群血浆脂质谱与2型糖尿病发病风险的关联研究

The rapidly developed epidemic trend of type 2 diabetes has become a major health challenge for Chinese people. Unhealthy diet and lifestyle are recognized as key drivers for epidemic trend of type 2 diabetes. Western studies have suggested the predictive role of lipidomic biomarkers in the risk of developing type 2 diabetes. However, evidence in Asian populations are limited. Our previous study suggested different concentration, related gene variants and disease associations of erythorocyte fatty acids compared with Western studies. Moreover, it is unknown whether the association between lipidomic biomarkers and diabetes could be modified by lifestyle and genetic variants relevant to lipids metabolism. Therefore, in an existing population-based prospective study of Chinese with genome-wide association study (GWAS) database and Exome chip database, we are going to measure plasma lipidomic profile by mass spectrometry, and aimed to investigate 1) the association between plasma lipidomic profile and the risk of developing type 2 diabetes; 2) the modifying effect of environmental factors including diet and genetic variants in the lipids metabolic pathway on the association; 3) potential mechanisms such as pancreatic islet function and chronic inflammation. Our study will provide novel insight for the etiologic role of nutrition and related genetic predispositions in the pathogenesis of type 2 diabetes in Chinese populations, and explore potential biomarkers for prevention and early intervention of type 2 diabetes.

快速流行的2型糖尿病严重威胁我国居民健康。脂代谢紊乱对2型糖尿病的发生发展起重要作用。西方研究提示血液脂质谱标志物可预测2型糖尿病的发病风险，但鲜见亚洲人群证据。本团队的前期靶向代谢组学研究提示：脂肪酸水平、基因及与疾病的关联可能存在中西方差异。此外，血液脂质谱与2型糖尿病的风险关联是否受到环境因素和脂代谢相关基因的影响，尚缺乏研究证据。因此，本项目将在已建立的队列人群和已有全基因组遗传关联研究和外显子组芯片数据库的基础上，采用质谱技术检测血浆脂质谱，重点研究1）血浆脂质谱与2型糖尿病发病风险的关联；2）膳食等环境因素和脂代谢相关基因变异与血浆脂质谱的关系，及对上述疾病关联的影响；3）胰岛功能和慢性炎症在上述疾病关联中的作用，探讨潜在机理。本项目首次在亚洲人群中系统研究血浆脂质谱、遗传多态性与2型糖尿病的风险关联，将有助于发现新的2型糖尿病早期预防和干预靶标，具有重要科学意义和应用价值。

快速流行的2型糖尿病严重威胁我国居民健康。脂代谢紊乱对2型糖尿病的发生发展起重要作用。西方研究提示血液脂质谱标志物可预测2型糖尿病的发病风险，但鲜见亚洲人群证据。本团队的前期靶向代谢组学研究提示：脂肪酸水平、基因及与疾病的关联可能存在中西方差异。此外，血液脂质谱与2型糖尿病的风险关联是否受到环境因素和脂代谢相关基因的影响，尚缺乏研究证据。本项目在已有的前瞻性研究和全基因组遗传多态性位点数据库基础上，发现29 种脂质（14种鞘脂，9种甘油酯和6种甘油磷脂）与6 年后新发2 型糖尿病风险显著相关，潜在机制可能是通过胰岛β细胞功能受损和肝脏脂肪累积发挥作用。孟德尔随机化研究还发现神经酰胺d18:1/20:1与2型糖尿病发病风险存在因果关系。本项目提示了特定脂质有可能作为2型糖尿病早期诊断和精准分型及精准干预的潜在标记物，为疾病的精准防诊治提供了新的思路和科学依据。