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: 10557795
• 负责人: Frank B Hu
• 金额: $ 46.64万
• 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/10557795
• 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; Random Allocation; Recommendation; Risk; Statistical Methods; Testing; Visceral; Woman; aged; comparison control; diabetes prevention program; diabetes risk; dietary; disorder prevention; fitness; follow-up; group intervention; gut microbiome; healthy lifestyle; improved; intervention effect; lifestyle intervention; men; metabolic profile; microbiome; multi-ethnic; non-diabetic; personalized intervention; precision nutrition; prospective; randomized, clinical trials; 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.

摘要 这项应用是Preedimed-Plus试验的辅助研究，以检查饮食和生活方式的影响 4770名非糖尿病患者中T2D作为次要终点的发生率的干预 在基线上。PREDIMED-Plus是一项正在进行的主要心血管预防试验(www.predimedplus.com)， 从2013年10月到12月，它招募了6874名男女(年龄在55岁到75岁之间) 2016年。参与者被随机分配到两组：减少能量的地中海饮食(MedDiet) 一组，接受体力活动和行为支持减肥；或对照组，接受低强度运动 关于MedDiet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 评估由能量减少的MedDiet组成的强化生活方式干预是否增加了 与对照组相比，体力活动和减肥可以降低T2D的发生率 (干预组n=2384；对照组n=2451)。第二，我们将评估生活方式的影响 双能X线测量总脂肪量和内脏脂肪组织的干预 对1,569名受试者进行1，3，6年干预后的骨密度测定(DXA)。第三，我们将审查 生活方式干预是否修改了代谢物风险评分(MRS)与 嵌套式病例对照研究中的T2D发生率(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，我们将考察干预是否会导致 从基线到第一年，250名参与者的粪便代谢物的有益变化 干预组250人，对照组250人。我们还将检查粪便代谢物的变化 与干预引起的肠道微生物群的变化有关。初步结果如下： PREDIMED-Plus参与者显示，干预显著降低了体重和糖化血红蛋白， 它持续了三年多。这项研究建立在一个大型随机对照试验的基础上，并将是第一个也是最大的 这是一种前瞻性评估强化生活方式干预对血浆和大便的影响 利用最先进的LC-MS平台和尖端生物信息学，研究代谢产物和T2D的风险 和统计方法。将使用客观测量来评估功能适合性(30秒的椅子坐- 体力活动(加速计)、身体成分(DXA)和特级初榨橄榄油 消费量(尿酪醇和羟基酪醇水平)。这个应用程序有可能推进我们的 了解T2D病理生理学，并告知精确营养和T2D预防。它具有重要的 对美国人口的影响，因为它可能提供进一步的证据来加强目前的 建议将MedDiet作为预防慢性病的健康生活方式的一部分。