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）：类型2糖尿病（DM）是主要来源 全球发病率和死亡率。 DM病例预计将在2025年上升72％ 影响所有国家和收入群体的3.25亿人。它越来越被认可 发展DM的个体之间存在表型异质性。一个子组 近年来，“瘦糖尿病”组引起了人们的特别关注，例如有个人 在没有肥胖症的情况下DM。 DM的精益人物的风险要高得多 与DM肥胖个体相比，死亡率和其他并发症。但是，鲜为人知 关于在没有肥胖症的情况下促进DM的因素，或 在此子集中的结果更糟。亚洲人特别容易发展精益DM。 大约一半发展DM的亚洲人被认为是正常体重（BMI小于25 kg/m2）。这种倾向独立于居住国，例如它影响生活在亚洲人 美国以及亚洲国家。实际上，美国的研究表明DM的率很高 在亚裔美国人中。 DM的发病机理反映了遗传的复杂相互作用， 饮食和环境暴露影响多种途径。一种方法 立即了解许多代谢途径的活性是代谢组学分析。 “代谢组学”是指生物标本中代谢物的系统分析，例如 等离子体。在人类种群中结合生物标志物和表型数据提供了丰富的 识别代谢疾病的生化特征的机会，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 非欧洲人群，尤其是亚洲队列，很少。差异 跨种族/族裔DM的流行病学表明了病理生理的可能性 差异。最近，在上海妇女健康研究（SWHS）的初步研究中 我们发现有证据表明中国妇女对DM有一些风险标记，与众不同 那些在欧洲人口中所描述的。因此，我们建议在我们的工作中大大扩展 在欧洲人口和我们在SWHS中的试点研究中，通过进行全面 在2个中国人群中进行代谢组学分析，以识别与之相关的代谢物 事件DM。我们的目的是（1）识别与中文事件DM相关的代谢产物 参加了SWHS和上海男子健康研究（SMHS）的个人； （2）到 在另一项病例研究中，复制代谢产物与事件DM的关联。