Dietary Interventions, Metabolites, and Risk of Type 2 Diabetes

饮食干预、代谢物和 2 型糖尿病的风险

基本信息

批准号：
8918612
负责人：
Frank B Hu
金额：
$ 48.19万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8918612
关键词：
Address Adult Affect Age Archives Aromatic Amino Acids Attention Attenuated Biological Biological Markers Blood specimen Body mass index Cell physiology Clinical Cohort Studies Control Groups Diabetes Mellitus Diabetes prevention Diagnosis Diet Dietary Intervention Dietary Practices Epidemic Fasting Fat-Restricted Diet Glutamine Goals Health Incidence Institutes Insulin Resistance Intervention Life Style Lipids Liquid Chromatography Massachusetts Measurement Measures Mediating Mediterranean Diet Metabolic Metabolic Pathway Non-Insulin-Dependent Diabetes Mellitus Nuts Obesity Olive oil preparation Outcome Participant Pathway interactions Plasma Prevention trial Primary Prevention Public Health Randomized Randomized Controlled Trials Recommendation Research Design Risk Risk Factors Sampling Spain Technology Time Trees acylcarnitine cohort cost effective design diabetes risk dietary supplements follow-up good diet gut microbiota intervention effect lifestyle factors lifestyle intervention metabolomics novel secondary outcome tandem mass spectrometry urea cycle

项目摘要

DESCRIPTION (provided by applicant): Type 2 diabetes (T2D) has reached epidemic proportion. Lifestyle factors such as a healthy diet are crucial for T2D prevention. Recently, the PREDIMED (PREvencion con DIeta MEDiterranea) trial was completed in Spain. The trial was a multicenter, randomized controlled trial in which 7,447 participants were randomly allocated to Mediterranean dietary interventions enriched with extra virgin olive oil or nuts or a control diet. Although the trial was primarily designed to assess the effect of the interventions on CVD, the dietary interventions also reduced incidence of T2D by 30% (95% CI 0.54-0.92). The goal of the present study is to examine whether the effects of Mediterranean diet on changes in metabolites and T2D risk. We will employ a case-cohort study design with 273 incident cases of T2D and 708 randomly selected participants free of diabetes at baseline (20%). Stored fasting blood specimens collected at baseline and at year 1 of the trial will be measured for a well-validated panel of ~300 metabolites, using the state-of-the-art LC-MS technology. Our Specific Aims are: 1) To examine the association between the baseline metabolite concentrations and the risk of T2D using a case-cohort design; 2). To examine whether the dietary interventions modify the relationships between baseline levels of metabolites and subsequent T2D risk using a case- cohort design; 3). To examine whether 1-year changes in metabolites mediate the effect of the dietary interventions on subsequent T2D outcomes from years 2 to 5 using a case-cohort design; and 4). To examine whether 1-year changes in metabolites influence insulin resistance and �-cell function from years 2 to 5 among 708 randomly selected participants free of diabetes at baseline. The large PREDIMED trial, with archived plasma samples and rich repeated measurements of diet, lifestyle, and biomarkers, represents an unprecedented opportunity to address our specific aims in an extremely cost-effective manner. This project has great potential to advance our understanding of the metabolic pathways through which dietary interventions influence T2D risk. It also has important public health and clinical implications because many of these metabolites and their associated pathways may be suitable for direct diet and lifestyle interventions. To prepare for this project, we have already completed a preliminary study by randomly selecting 20 samples from each diet group at one year of intervention and conducted metabolomic analyses using LC-MS at the Broad Institute of MIT and Harvard.

描述（适用提供）：2型糖尿病（T2D）已达到流行比例。健康饮食等生活方式因素对于预防T2D至关重要。最近，在西班牙完成了Predimed（预防饮食中地中海）试验。该试验是一项多中心，随机对照试验，在该试验中，将7,447名参与者随机分配给富含特级初榨橄榄油或坚果或对照饮食的地中海饮食干预措施。尽管该试验主要旨在评估干预措施对CVD的影响，但饮食干预措施也将T2D的事件降低了30％（95％CI 0.54-0.92）。本研究的目的是检查地中海饮食对代谢物变化和T2D风险的影响。我们将采用一个病例研究设计设计，其中有273例T2D事故病例和708个在基线时没有糖尿病的随机选择的参与者（20％）。使用最先进的LC-MS技术，将在基线上收集的储存的禁食标本和试验的第1年。我们的具体目的是：1）检查基线代谢物浓度与使用案例 - 霍特设计的T2D风险之间的关联； 2）。检查饮食干预措施是否改变了使用案例 - 霍特设计的代谢产物基线水平与随后的T2D风险之间的关系； 3）。检查代谢物的一年变化是否介导了使用案例 - 霍特设计的饮食干预措施对从2年到5年的T2D结果的影响；和4）。为了检查代谢产物的一年变化是否影响708名随机选择的参与者中的胰岛素抵抗和``cell功能''在基线时没有糖尿病。大型Predimed试验具有存档的等离子体样本以及对饮食，生活方式和生物标志物的丰富重复测量，这是一个前所未有的机会，可以以极其成本效益的方式解决我们的特定目标。该项目具有巨大的潜力，可以促进我们对饮食干预影响T2D风险的代谢途径的理解。它也具有重要的公共卫生和临床意义，因为这些代谢产物中的许多及其相关途径可能适合直接饮食和生活方式干预。为了准备该项目，我们已经完成了一项初步研究，通过在干预的一年中随机从每个饮食组中随机选择20个样本，并在麻省理工学院和哈佛大学广泛研究所使用LC-MS进行了代谢组分分析。