Development of obesity and metabolic clinical research programs

肥胖和代谢临床研究项目的开发

• 批准号: 8349918
• 负责人: Kong Chen
• 金额: $ 43.91万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349918
• 关键词: Air; Area; Body Composition; Body Weight; Carbon Dioxide; Cardiovascular system; Cessation of life; Characteristics; Chronic; Clinical Protocols; Clinical Research; Consent; Data; Data Analyses; Data Collection; Databases; Development; Diet; Energy Intake; Energy Metabolism; Enrollment; Environment; Epidemic; Equilibrium; Evaluation; Exercise; Family; Functional disorder; Generations; Goals; Gold; Health; Heating; Human; Humidity; Iceland; Indirect Calorimetry; Inpatients; International; Knowledge; Laboratories; Length; Life; Manuscripts; Measurement; Measures; Metabolic; Methods; Metric; Modification; Monitor; Morphologic artifacts; National Health and Nutrition Examination Survey; Netherlands; Obesity; Outpatients; Overweight; Oxygen; Patient Recruitments; Performance; Phenotype; Physical Function; Physical activity; Population; Predisposition; Preparation; Process; Property; Protocols documentation; Quality Control; Reaction Time; Recruitment Activity; Regulation; Research; Research Personnel; Resistance; Respiration; Rest; Running; Screening procedure; Series; Sleep; System; Techniques; Telephone; Temperature; Thermogenesis; Time; United States National Institutes of Health; Variant; Weight; Weight Gain; Work; aging gene; bone health; cognitive function; design; energy balance; experience; field study; fitness; improved; insight; interest; meetings; men; model development; muscle metabolism; non-compliance; older women; programs; response; sensor; symposium; tool; volunteer

For the first aim, we have made progress in the following three areas. 1. Indirect calorimeters are gold-standard measurements of energy expenditure. However, standard measurements using metabolic carts limit to only short time measurements such as 30-minute basal or exercise conditions. Whole-room calorimeters (respiration chambers) expand our ability to study humans in near free-living conditions and allow us to separate out different components of energy expenditure (e.g., sleeping vs. resting, activity vs. postprandial). The major limitation of the chambers is the larger size (20-30 m3) reduces its sensitivity and response time, and allows environmental artifacts. We have been systematically evaluating our whole-room indirect calorimetry chamber systems since their inception (2008) and through a series of modifications we performed in FY 2011. We measured specific impacts from inlet air supply, outgoing flow characteristics, temperature, humidity, and filtering on the measurements of oxygen and carbon dioxide. Ultimately, we are using this knowledge to optimize the chamber performances (accuracy, precision, and response time). The data will be presented at the 2nd international conference on Recent Advances and Controversies in Measuring Energy Metabolism (Nov 2-4, Maastricht, The Netherlands). 2. For accurate free-living physical activity measurements, portable accelerometers are the gold-standard objective technique. This is a fast-developing field, both in sensor designs and in data analyses. We developed a universal calibrator from a standard bench-top orbital shaker, and evaluated the technical and field applicability of two new generation physical activity monitors (Actigraph GT3X+ and GENEActive G3) for the National Health and Nutrition Examination Survey (NHANES 2011-12) study. We designed specific metrics for studying the properties of these monitors for the NHANES field applications, while drawing experiences and expertise from our previous work with sensor designs (Chen et al. 2011), model development (Van Hees et al. 2011), and analysis of the NHANES field data from 2003-2006 (Bankoski et al. 2011). Working closely with our NCI and NHANES collaborators, we selected the monitor that met the major needs of NHANES, and has been working on continue evaluation the monitor (1800 units in the field) and quality control during the 2-year data collection process. 3. We continue to work with our Iceland and NIA investigators on the free-living physical activity and sleep assessment data we collected for the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study from March 2009 to July 2010. We have cleaned the activity and sleep data, extracted parameters relevant to metabolic health and function, such as total amount of physical activity and moderate to vigorous activity times. We are analyzing these parameters with combined measures from the large database such as cardiovascular health, bone and muscle, metabolism, and cognitive function. Two manuscripts are in preparations. For the second aim, we made every effort in recruiting study volunteers for the clinical protocol titled Diet-Induced-Obesity Resistant Phenotypes in Humans (09-DK-0238), with the goal of identifying healthy lean subjects who are resistant (gain less than 25% of weight as predicted) to hypercaloric diets for 4 weeks (+1000 kcal/day over weight balanced diets). During FY11, we have phone-screened 32 potential volunteers (referred either by NIH Patient Recruitment office, flyers, word of mouth, or by direct contact). We consented 4 subjects for outpatient screening, and two study volunteers have enrolled. Unfortunately, both subject decided to withdraw voluntarily after the first week of study, one due to dietary noncompliance issue, and the other had a family death. The major factor impacted accrual has been the commitment to the study length (5 weeks of inpatient study + one month run-in period). After discussions with our Branch Chief Dr. Marc Reitman, we decided to temporarily halt further recruitment of new study volunteers and reevaluate the protocol. We have developed a new clinical protocol titled Energy expenditure responses to a range of environmental temperatures around the thermal neutral zone, which is the temperature region where heat production (energy expenditure)is a minimum and does not vary with environmental temperature. Surprisingly, little is understood about how the body regulates heat production (and thus energy expenditure) in response to subtle changes in environmental temperature and about the population variation in these processes. It is plausible that the mechanisms governing heat production contribute to regulation of body weight. Thus understanding these control mechanisms should provide insight into the pathophysiology underlying the current epidemic of obesity. The primary goals of this study are to develop metrics to study resting energy expenditure responses to change in temperature, both cold and hot, and establish the ranges of such responses in normal lean and obese, young and old, women and men. While this topic has interested many over decades, we were unaware of detailed data in heat and energy balances over multiple temperature points and in different subject populations. We plan to start the protocol in FY12.

为了第一个目标，我们在以下三个领域取得了进步。 1。间接热量表是能量消耗的金标准测量值。但是，使用代谢推车使用的标准测量仅限于短时测量，例如30分钟的基础或运动条件。全室量热量器（呼吸室）扩大了我们在几乎自由生活条件下学习人类的能力，并使我们能够将不同的能量消耗组成部分分开（例如，睡眠与休息，活动与餐后的活动）。腔室的主要局限性是较大的尺寸（20-30 m3）降低了其灵敏度和响应时间，并允许环境伪像。 自成立（2008）以来，我们一直在系统地评估整个房间间接量热法室系统，并通过一系列修改我们在2011财年进行的一系列修改。我们衡量了进气供应，外向流动特性，温度，湿度，湿度以及氧化和二氧化碳测量的特定影响。 最终，我们正在利用这些知识来优化室内的性能（准确性，精度和响应时间）。该数据将在第二届国际衡量能源代谢的进步和争议的第二届国际会议上介绍（11月2-4日，马斯特里奇，荷兰）。 2。对于准确的自由运动测量值，便携式加速度计是金标准目标技术。这是一个快速发展的领域，无论是在传感器设计还是在数据分析中。我们从标准的台式轨道振动器开发了一种通用校准器，并评估了国家健康和营养检查调查（NHANES 2011-12）的两个新一代体育活动监测器（Actigraph GT3X+和遗传性G3）的技术和现场适用性。我们设计了特定的指标，用于研究NHANES现场应用的这些监视器的性质，同时从我们先前使用传感器设计的工作中汲取了经验和专业知识（Chen等，2011），模型开发（Van Hees等，2011），并分析了2003-2006的NHANES现场数据（Bankoski等人2011年）。与我们的NCI和NHANES合作者紧密合作，我们选择了满足NHANES的主要需求的监视器，并一直在继续评估监视器（现场1800个单位）和在2年数据收集过程中质量控制。 3。我们继续与我们的冰岛和NIA调查人员一起研究我们为年龄，基因/环境易感性-Reykjavik研究收集的自由生活的体育锻炼和睡眠评估数据（2009年3月至2010年3月至2010年7月，我们已经清理了与分泌健康的活动，并适应了这些参数，并适应了这些参数，并适应了这些活动，并适应了这些参数，并适应了这些参数，并适应了这些参数，并适应了这些参数，并适应了这些参数，并适应了这些参数，并适应了这些参数，并适应了这些参数。大型数据库的综合度量，例如心血管健康，骨骼和肌肉，代谢和认知功能。 为了第二个目标，我们为人类的临床协议招募了志愿者招募研究志愿者（09-DK-0238），目的是识别抗抗性的健康精益受试者（根据预测的体重增加的25％）到4周的高度饮食（+1000 kcal day）（+1000 kcal day）的体重（+1000 kcal day）。在2011财年期间，我们有电话筛选了32名潜在志愿者（由NIH患者招聘办公室，传单，口口相传或直接联系）。我们同意4名受试者进行门诊筛查，并参与了两名研究志愿者。不幸的是，两个受试者在学习的第一周后决定自愿撤回，一个是由于饮食不合规问题，另一个是家庭死亡。 影响应计的主要因素是对研究长度的承诺（住院研究5周 +一个月的磨合期）。在与分支机构负责人马克·雷特曼（Marc Reitman）博士讨论之后，我们决定暂时停止进一步招募新的研究志愿者并重新评估该协议。 我们已经开发了一种新的临床协议，标题为对热中性区域周围一系列环境温度的能量消耗响应，这是热量产生（能量消耗）最小的温度区域，并且随环境温度不变。 令人惊讶的是，关于人体如何调节热量产生（以及能量消耗），这对环境温度的细微变化以及这些过程中的种群变化几乎没有理解。控制热量产生的机制有助于调节体重是合理的。 因此，了解这些控制机制应提供对当前肥胖流行病基础的病理生理学的见解。 这项研究的主要目标是制定指标，以研究对温度变化（冷和热）的静息能量消耗的反应，并在正常的瘦和肥胖，年轻人和老年人，男女中建立这种反应的范围。尽管这个主题具有数十年的感兴趣，但我们并未意识到在多个温度点和不同受试者人群中的热量和能量平衡中的详细数据。我们计划在FY12中启动该协议。