Lifestyle Interventions, metabolites, microbiome, and diabetes risk

生活方式干预、代谢物、微生物组和糖尿病风险

• 批准号: 10370323
• 负责人: Frank B Hu
• 金额: $ 48.27万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370323
• 关键词: Accelerometer; Adipose tissue; Ancillary Study; Attenuated; Behavioral; Bioinformatics; Body Composition; Body Weight; Body Weight decreased; Cardiovascular system; Chronic Disease; Consumption; Control Groups; Development; Diabetes prevention; Diet; Dietary Intervention; Dual-Energy X-Ray Absorptiometry; Fatty acid glycerol esters; Feces; Functional disorder; Glycosylated hemoglobin A; Grant; Incidence; Individual; Intervention; Life Style; Measures; Mediating; Mediterranean Diet; Metabolic Pathway; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; Olive oil preparation; Participant; Physical Fitness; Physical activity; Placebos; Plasma; Population; Prevention; Prevention trial; Randomized Clinical Trials; Recommendation; Risk; Statistical Methods; Testing; Visceral; Woman; aged; diabetes prevention program; diabetes risk; dietary; disorder prevention; fitness; follow-up; group intervention; gut microbiome; healthy lifestyle; intervention effect; lifestyle intervention; men; metabolic profile; microbiome; multi-ethnic; non-diabetic; precision nutrition; prospective; recruit; secondary endpoint; stool sample; tyrosol; urinary

Abstract This application is an ancillary study of the PREDIMED-Plus trial to examine the effects of a diet and lifestyle intervention on incidence of T2D as a secondary endpoint among 4,770 participants who were non-diabetics at baseline. PREDIMED-Plus is an ongoing primary cardiovascular prevention trial (www.predimedplus.com), which has recruited 6,874 women and men (aged 55 to 75 years) between October 2013 and December 2016. Participants were randomly allocated to 2 groups: an energy-reduced Mediterranean diet (MedDiet) group, with physical activity and behavioral support for weight loss; or a control group receiving low-intensity advice on the MedDiet. The intervention will last 6 years. We will examine four Specific Aims. First, we will evaluate whether an intensive lifestyle intervention consisting of an energy-reduced MedDiet, increased physical activity, and weight loss, reduces the incidence of T2D comparied with the control group (intervention group n=2,384; control group n=2,451). Second, we will evaluate the effect of the lifestyle intervention on total fat mass and visceral adipose tissue (VAT) measured by Dual-energy X-ray Absorptiometry (DXA) after 1, 3, and 6-year intervention in a subsample (n=1,569). Third, we will examine whether the lifestyle intervention modifies the association of the metabolite risk score (MRS) with the incidence of T2D in a nested case-control study (n=620 incident T2D cases and 620 matched controls). These analyses will be replicated in the multi-ethnic US Diabetes Prevention Program (DPP, 775 cases and 1,386 non-cases from the placebo/lifestyle groups). Fourth, we will examine whether the intervention induces beneficial changes in stool metabolites from baseline to year 1, in a subsample of 250 participants in the intervention group and 250 in the control group. We will also examine whether changes in stool metabolites are associated with changes in gut microbiome induced by the intervention. The preliminary results among the PREDIMED-Plus participants showed that the intervention significantly reduced body weight and HbA1c, which was sustained over three years. This study builds upon a large RCT and will be the first and largest of its kind to prospectively assess the effects of an intensive lifestyle intervention on plasma and stool metabolites and the risk of T2D, using the state-of-the-art LC-MS platform and cutting-edge bioinformatics and statistical methods. Objective measures will be used to assess functional fitness (a 30-second chair sit- and-stand (CSS) test), physical activity (accelerometers), body composition (DXA), and extra-virgin olive oil consumption (urinary tyrosol and hydroxytyrosol levels). This application has the potential to advance our understanding of T2D pathophysiology and inform precision nutrition and T2D prevention. It has important implications for the US population because it may provide further evidence to strengthen current recommendations on the MedDiet as a part of a healthy lifestyle for chronic disease prevention.

抽象的 该应用程序是 PREDIMED-Plus 试验的辅助研究，旨在检查饮食和生活方式的影响 对 4,770 名非糖尿病参与者的 T2D 发病率进行干预作为次要终点 在基线。 PREDIMED-Plus 是一项正在进行的初级心血管预防试验 (www.predimedplus.com)， 2013 年 10 月至 12 月期间，已招募了 6,874 名女性和男性（年龄 55 至 75 岁） 2016 年。参与者被随机分为 2 组：低能量地中海饮食 (MedDiet) 小组，进行体力活动和减肥行为支持；或对照组接受低强度 关于医学饮食的建议。干预将持续6年。我们将研究四个具体目标。首先，我们将 评估由减少能量的医疗饮食组成的强化生活方式干预是否可以增加 与对照组相比，体力活动和体重减轻可降低 T2D 的发病率 （干预组 n=2,384；对照组 n=2,451）。其次，我们会评估生活方式的影响 双能X射线测量总脂肪量和内脏脂肪组织（VAT）的干预 对子样本 (n=1,569) 进行 1 年、3 年和 6 年干预后的吸光光度测定 (DXA)。第三，我们将检查 生活方式干预是否会改变代谢物风险评分（MRS）与 巢式病例对照研究中 T2D 的发病率（n=620 例 T2D 病例和 620 例匹配对照）。 这些分析将在美国多种族糖尿病预防计划（DPP，775 例和 来自安慰剂/生活方式组的 1,386 例非病例）。第四，我们将检查干预是否会导致 在 250 名参与者的子样本中，粪便代谢物从基线到第一年的有益变化 干预组和对照组各250人。我们还将检查粪便代谢物是否发生变化 与干预引起的肠道微生物组的变化有关。初步结果其中 PREDIMED-Plus 参与者表明，干预措施显着降低了体重和 HbA1c， 这种情况持续了三年多。这项研究建立在大型随机对照试验的基础上，并且将是第一个也是最大的 它前瞻性地评估强化生活方式干预对血浆和粪便的影响 使用最先进的 LC-MS 平台和尖端生物信息学研究代谢物和 T2D 风险 和统计方法。将使用客观措施来评估功能健康（在椅子上坐 30 秒） 站立 (CSS) 测试）、体力活动（加速度计）、身体成分 (DXA) 和特级初榨橄榄油 消耗（尿液酪醇和羟基酪醇水平）。该应用程序有潜力推进我们的 了解 T2D 病理生理学并为精准营养和 T2D 预防提供信息。它有重要的 对美国民众的影响，因为它可能提供进一步的证据来加强当前的 关于将医疗饮食作为预防慢性病的健康生活方式的一部分的建议。