Metabolite profiles and the risk of diabetes in Asians

亚洲人的代谢特征和糖尿病风险

• 批准号: 10227610
• 负责人: ROBERT E GERSZTEN
• 金额: $ 19.11万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-10 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227610
• 关键词: Metabolite; profiles; risk; diabetes; Asians

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus (DM) is a major source of morbidity and mortality worldwide. Cases of DM are expected to rise by 72% through 2025, affecting 325 million people across all nations and income groups. It is increasingly recognized that there is phenotypic heterogeneity among individuals who develop DM. One subgroup that has attracted particular attention in recent years is the "lean diabetes" group, e.g. individuals with DM in the absence of obesity. Lean individuals with DM are at substantially higher risk of mortality and other complications than obese individuals with DM. However, little is known about the factors that promote DM in the absence of obesity, or the mechanisms underlying the worse outcomes in this subset. Asians are particularly susceptible to developing lean DM. Approximately half of Asians who develop DM are considered normal weight (BMI less than 25 kg/m2). This propensity is independent of country of residence, e.g. it affects Asians living in th U.S. as well as in Asian countries. Indeed, studies in the U.S. indicate very high rates of DM among Asian-Americans. The pathogenesis of DM reflects a complex interplay of genetic, dietary, and environmental exposures affecting multiple pathways. One approach to understanding the activity in many metabolic pathways at once is metabolomics profiling. "Metabolomics" refers to the systematic analysis of metabolites in a biological specimen, such as plasma. Combining biomarker and phenotypic data in human populations provides a rich opportunity to identify the biochemical signatures of metabolic diseases, which can enhance biological understanding as well as yield tools for disease screening. Metabolomics data from non-European cohorts, and particularly Asian cohorts, are sparse. The differences in the epidemiology of DM across racial/ethnic groups suggest the possibility of pathophysiological differences. Recently, in a preliminary study in the Shanghai Women's Health Study (SWHS), we found evidence that Chinese women had some risk markers for DM that were distinct from those described in European populations. Thus, we propose to expand considerably on our work in European populations and our pilot studies in the SWHS, by performing comprehensive metabolomics profiling in 2 Chinese cohorts to identify metabolites that are associated with incident DM. Our aims are (1) to identify metabolites that associate with incident DM in Chinese individuals enrolled in the SWHS and Shanghai Men's Health Study (SMHS); and (2) to replicate the association of metabolites with incident DM in a separate case-cohort study.

描述（由申请人提供）：2 型糖尿病 (DM) 是糖尿病的主要来源 全世界的发病率和死亡率。到 2025 年，糖尿病病例预计将增加 72%， 影响所有国家和收入群体的 3.25 亿人。越来越被人们认可 患有糖尿病的个体之间存在表型异质性。一个子群 近年来特别引起关注的是“瘦糖尿病”群体，例如个人与 没有肥胖的糖尿病。患有 DM 的瘦人患糖尿病的风险要高得多 死亡率和其他并发症高于肥胖糖尿病患者。然而，鲜为人知 关于在没有肥胖的情况下促进 DM 的因素，或潜在的机制 该子集中的结果更差。亚洲人特别容易患瘦型糖尿病。 大约一半患有糖尿病的亚洲人体重正常（BMI 低于 25） 千克/平方米）。这种倾向与居住国家/地区无关，例如它影响了生活在这个国家的亚洲人 美国以及亚洲国家。事实上，美国的研究表明糖尿病发病率非常高 在亚裔美国人中。 DM 的发病机制反映了遗传、 饮食和环境暴露影响多种途径。一种方法 同时了解许多代谢途径的活动就是代谢组学分析。 “代谢组学”是指对生物样本中代谢物的系统分析，例如 等离子体。结合人群中的生物标志物和表型数据提供了丰富的信息 有机会识别代谢疾病的生化特征，这可以增强 生物学理解以及疾病筛查的产量工具。代谢组学数据来自 非欧洲群体，尤其是亚洲群体，数量很少。差异在于 跨种族/族裔群体的 DM 流行病学表明病理生理学的可能性 差异。最近，上海女性健康研究（SWHS）的一项初步研究显示， 我们发现有证据表明，中国女性有一些与女性不同的糖尿病风险标记 欧洲人群中描述的那些。因此，我们建议大幅扩展我们的工作 在欧洲人群中以及我们在 SWHS 中的试点研究中，通过进行全面的 对 2 个中国队列进行代谢组学分析，以确定与 事件DM。我们的目标是 (1) 识别与中文糖尿病事件相关的代谢物 参加 SWHS 和上海男性健康研究 (SMHS) 的个人； (2) 至 在一项单独的病例队列研究中复制了代谢物与糖尿病发病之间的关联。