Metabolite profiles and the risk of diabetes in Asians

描述(申请人提供)：2型糖尿病(DM)是 世界范围内的发病率和死亡率。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。越来越多的人认识到 患有DM的个体之间存在表型异质性。其中一个亚群 近年来引起特别关注的是“瘦身糖尿病”群体，例如患有 糖尿病在没有肥胖的情况下。患有糖尿病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糖尿病肥胖者。然而，人们对此知之甚少 在没有肥胖的情况下促进糖尿病的因素，或潜在的机制 这一子集的结果更糟。亚洲人特别容易患上精益DM。 大约一半患有糖尿病的亚洲人被认为是正常体重(BMI小于25 Kg/m2)。这种倾向与居住国无关，例如，它会影响生活在 美国和亚洲国家也是如此。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一种复杂的遗传、 影响多种途径的饮食和环境暴露。一种方法是 同时了解许多代谢途径中的活性是代谢组学的特征。 “代谢组学”是指对生物样本中的代谢物进行系统分析，例如 血浆。结合生物标志物和人类群体的表型数据提供了丰富的 有机会确定代谢性疾病的生化特征，这可以增强 对生物学的理解以及用于疾病筛查的有效工具。代谢组学数据来自 非欧洲人群，尤其是亚洲人群，数量稀少。两个国家之间的差异 糖尿病跨种族/民族的流行病学表明，病理生理学可能 不同之处。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，中国女性有一些不同于 那些在欧洲人口中描述的。因此，我们建议大大扩大我们的工作。 在欧洲人口和我们在SWHS的试点研究中，通过执行全面的 在2个中国队列中进行代谢组学分析以确定与以下因素相关的代谢物 事件DM。我们的目标是(1)确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)的个人；及 在另一项病例队列研究中重复代谢物与糖尿病发病的关系。

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.