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。 发病率和死亡率。预计到2025年，糖尿病病例将增加72%， 影响到所有国家和收入群体的3.25亿人。人们日益认识 在糖尿病患者中存在表型异质性。一个亚组， 近年来引起特别关注的是"瘦型糖尿病"组，例如， 糖尿病在没有肥胖的情况下。患有DM的瘦型个体患糖尿病的风险显著较高， 死亡率和其他并发症。然而， 关于在没有肥胖的情况下促进糖尿病的因素，或糖尿病的潜在机制， 在这个子集中的结果更糟。亚洲人特别容易患瘦型糖尿病。 大约一半的亚洲糖尿病患者体重正常（BMI小于25 kg/m2）。这种倾向与居住国无关，例如，它影响居住在美国的亚洲人。 美国在亚洲国家也是如此。事实上，美国的研究表明，糖尿病的发病率非常高， 在亚裔美国人中。糖尿病的发病机制反映了遗传， 饮食和环境暴露影响多种途径。的一种方法 同时了解许多代谢途径的活性是代谢组学分析。 "代谢组学"是指对生物样本中的代谢物进行系统分析，例如 等离子体结合人群中的生物标志物和表型数据， 有机会确定代谢性疾病的生化特征，这可以提高 生物学理解以及疾病筛查的产量工具。代谢组学数据来自 非欧洲人，特别是亚洲人，数量稀少。的差异 不同种族/民族的糖尿病流行病学表明， 差异最近，在上海妇女健康研究（SWHS）的一项初步研究中， 我们发现有证据表明，中国女性有一些糖尿病的风险标志物， 在欧洲人群中描述的那些。因此，我们建议大大扩展我们的工作， 在欧洲人群和我们在SWHS的试点研究中，通过进行全面的 在2个中国队列中进行代谢组学分析，以确定与 事件DM。我们的目的是：（1）鉴定与中国人糖尿病发病相关的代谢物 参加SWHS和上海男性健康研究（SMHS）的个体;以及（2） 在一项单独的病例队列研究中重复代谢产物与糖尿病发病的相关性。