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.

抽象的 该应用是对Predimed-Plus试验的辅助研究，以检查饮食和生活方式的影响 在4,770名非糖尿病的参与者中，T2D的发生率是二次终点 基线。 Predimed-Plus是一项持续的主要心血管预防试验（www.predimedplus.com）， 在2013年10月至12月之间，已招募了6,874名男女（55至75岁） 2016年。将参与者随机分配给2组：减少能量的地中海饮食（Meddiet） 小组，具有体育锻炼和为体重减轻的行为支持；或接收低强度的对照组 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，我们会的 评估包括减少能量的医学会增加的密集生活方式干预措施是否增加 体育锻炼和体重减轻，降低了与对照组相比的T2D的发生率 （干预组n = 2,384;对照组n = 2,451）。第二，我们将评估生活方式的影响 通过双能量X射线测量的总脂肪质量和内脏脂肪组织（VAT）的干预 在子样本中1、3和6年干预后的吸收法（DXA）（n = 1,569）。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 在嵌套的病例对照研究中T2D的发生率（n = 620个事件T2D病例和620个匹配的对照）。 这些分析将在多种族的美国糖尿病预防计划中复制（DPP，775例和 安慰剂/生活方式组的1,386个非案例）。第四，我们将检查干预措施是否引起 从基线到第1年的粪便代谢产物的有益变化，在250名参与者的子样本中 干预组，对照组为250。我们还将检查粪便代谢物的变化是否 与干预诱导的肠道微生物组的变化有关。初步结果 PERIMED-PLUS参与者表明，干预措施显着降低了体重和HBA1C，， 这持续了三年。这项研究以大型RCT为基础，将是最大的也是最大的 这是一种预期评估强化生活方式干预对等离子体和粪便的影响 使用最先进的LC-MS平台和尖端的生物信息学的代谢物和T2D的风险 和统计方法。客观措施将用于评估功能适应性（30秒的椅子位置 - 和 - 固定测试），体育活动（加速度计），身体成分（DXA）和特定效果橄榄油 消费（尿酪醇和羟基苯基醇水平）。该应用程序有可能提高我们的 了解T2D病理生理学并为精确营养和T2D预防提供信息。它很重要 对美国人口的影响，因为它可能会提供进一步的证据来加强当前 关于Meddiet的建议是预防慢性疾病的健康生活方式的一部分。