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.

摘要 本申请是PREDIMED-Plus试验的辅助研究，旨在检查饮食和生活方式的影响 在4，770名非糖尿病受试者中对T2 D发生率进行干预作为次要终点 在基线。PREDIMED-Plus是一项正在进行的一级心血管预防试验（www.predimedplus.com）， 该组织在2013年10月至2014年12月期间招募了6，874名女性和男性（年龄在55至75岁之间） 2016.参与者被随机分配到2组：能量减少的地中海饮食（MedDiet） 一组，通过身体活动和行为支持减肥;或对照组接受低强度 关于MedDiet的建议干预将持续6年。我们将研究四个具体目标。一是 评估是否强化生活方式干预，包括能量减少的MedDiet，增加 与对照组相比，体力活动和体重减轻降低了T2 D的发病率 （干预组n= 2，384;对照组n= 2，451）。其次，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干预研究 在子样本（n= 1，569）中进行1年、3年和6年干预后的吸光度测定（DXA）。第三，我们将研究 生活方式干预是否改变代谢物风险评分（MRS）与 一项巢式病例对照研究中T2 D的发病率（n=620例T2 D发病病例和620例匹配对照）。 这些分析将在多种族的美国糖尿病预防项目（DPP，775例， 安慰剂/生活方式组的1，386例非病例）。第四，我们将研究干预是否会导致 在250名参与者的子样本中，从基线到第1年粪便代谢物的有益变化， 对照组250例。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组变化有关。初步结果显示， PREDIMED-Plus参与者显示干预显著降低了体重和HbA 1c， 持续了三年多这项研究建立在一个大型RCT的基础上，将是第一个也是最大的 前瞻性评估强化生活方式干预对血浆和粪便的影响 代谢物和T2 D风险，使用最先进的LC-MS平台和尖端的生物信息学 和统计方法。客观的措施将被用来评估功能健康（30秒的椅子坐， 站立（CSS）测试），身体活动（加速计），身体成分（DXA）和特级初榨橄榄油 消耗（尿酪醇和羟基酪醇水平）。这个应用程序有可能推动我们的 了解T2 D病理生理学，并为精确营养和T2 D预防提供信息。具有重要 对美国人口的影响，因为它可能提供进一步的证据，以加强目前的 建议将MedDiet作为预防慢性病的健康生活方式的一部分。