Dramatic Improvements to the Doubly Labeled Water Technique by Measurement of 17O

通过测量 17O 显着改进双标记水技术

• 批准号: 8592201
• 负责人: Elena S Berman
• 金额: $ 41.7万
• 依托单位: LOS GATOS RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-10 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8592201
• 关键词: Accounting; Algorithms; Blood; Businesses; Calibration; Chronic Disease; Clinical; Computer software; Conduct Clinical Trials; Consumption; Cost Savings; Data Analyses; Development; Energy Metabolism; Epidemic; Funding; Gold; High Prevalence; Housing; Human; Individual; Isotopes; Label; Laboratories; Lasers; Legal patent; Life; Liquid substance; Marketing; Mass Spectrum Analysis; Measurement; Measures; Medical; Medicine; Memory; Metabolic; Methods; Modeling; Monitor; Obesity; Output; Overweight; Phase; Plasma; Play; Population Study; Public Health; Research; Research Personnel; Research Project Grants; Risk; Role; Sampling; Secure; Source; Spectrum Analysis; Technical Expertise; Techniques; Technology; Testing; Time; Urine; Water; Work; base; cost; design; improved; innovation; instrument; metabolic abnormality assessment; novel; professor; public health relevance; research study; standard measure; stem; treatment center; water testing

DESCRIPTION (provided by applicant): The high prevalence of obesity in the US is a major public health concern, as overweight and obese individuals are at increased risk for many chronic diseases. Obesity stems from an imbalance between total caloric consumption and total energy expenditure (TEE), therefore accurate measurements of TEE play a pivotal role in understanding and ultimately reversing this epidemic. The gold standard for measuring TEE in free-living individuals is the doubly labeled water (DLW) method; major limitations of the method include high cost and precision of only ¿ 7% for individual measurements. In this Small Business Innovative Research (SBIR) project, Los Gatos Research (LGR) will develop, fabricate, and test a novel, laser-based analyzer based on LGR's patented, laser-based Off-Axis Integrated Cavity Output Spectroscopy technology to dramatically improve DLW measurements of TEE by measuring 17O/16O to correct for natural isotopic fluctuations in 18O and 2H. The Triple Isotope Water Analyzer (TIWA) will be capable of real-time, simultaneous, high-throughput (45 samples/day) monitoring of 2H/1H, 18O/16O, and 17O/16O in H2O from human bodily fluids, with a target accuracy and precision of better than ¿0.6% for 2H/1H, ¿0.15% for 18O/16O, and ¿0.2% for 17O/16O at natural isotopic abundances. For enriched body waters that have been labeled with 2H and 18O, the accuracy and precision will be comparable to IRMS and better than ¿1.0% for 2H/1H and ¿0.2% for 18O/16O. By measuring 17O/16O, the TIWA will allow quantification of isotopic background fluctuation in 18O/16O and 2H/1H during DLW measurements of TEE, thus eliminating the significant "constant background" assumption made during DLW experiments, and thereby improving measurement precision and significantly reducing the cost of TEE experiments. Based on the excellent correlation measured during Phase I, we estimate that measurement of the isotopic background fluctuation will result in a 40% increase in the precision of DLW tests of TEE, allowing for smaller study sizes while maintaining the statistical power of the measurements and reducing study costs by an estimated 72%! Additionally, the improved precision introduces the possibility of extending this technique from population studies to the accurate assessment of the TEE of a single subject. During Phase II, LGR will continue to work with Prof. Edward Melanson and Prof. John Speakman to demonstrate and apply an improved instrument for simultaneous isotope measurements using minimally prepared, human urine samples. TEE will be measured using the improved, triple isotope method and the results compared with simultaneous, gold-standard measurement of TEE in a metabolic chamber, standard DLW as measured by IRMS, and standard DLW as measured using laser-based isotope analysis. At the conclusion of this research project, LGR will have demonstrated the use of the TIWA for triple-isotope DLW measurements and empirically determined the improvement in TEE accuracy and reduction in the DLW method cost due to the measurement of background fluctuation using 17O/16O.

描述（由适用提供）：美国肥胖症的高流行率是一个主要的公共卫生问题，因为超重和肥胖的人对许多慢性疾病的风险增加。肥胖植物从总热量消耗和总能量消耗（TEE）之间的不平衡，因此，准确的TEE测量在理解和最终逆转这种流行病方面起着关键作用。在自由生活个体中测量T恤的金标准是双标记水（DLW）方法；该方法的主要局限性包括高成本和精度仅为单个测量值7％。在这项小型企业创新研究（SBIR）项目中，Los Gatos研究（LGR）将基于LGR的基于LASER的基于激光的非轴外腔输出频谱技术来开发，制造和测试基于激光的分析仪，以通过测量17o/16o的DLW测量，以促进17O/16O的自然效率，以符合自然效率和2的fluct，从而极大地改善了TEE的DLW测量。三倍同位素水分析仪（TIWA）将能够对2H/1H，18O/16O，18O/16O和17o/16o进行实时，同时，高通量（45个样本/天）监测，从人体体液中进行H2O中的17O/16O，对于2H/1H的目标准确性和0.6％的目标和精度，且准确性为0.6％。天然同位素丰度的17o/16o。对于已标记为2H和18O的富集体水，准确性和精度将与IRM相当，而2H/1H的准确性和精度将比1.0％优于1.0％，而18o/16o的准确性和精度为0.2％。通过测量17o/16o，TIWA将允许在TEE的DLW测量过程中定量18O/16O和2H/1H中的同位素背景波动，从而消除了DLW实验过程中显着的“恒定背景”假设，从而可以改善测量精度并显着降低TEE的成本。基于在第一阶段测得的出色相关性，我们估计同位素背景波动的测量将导致TEE的DLW测试精确度增加40％，从而使研究尺寸较小，同时维持测量的统计能力，并降低研究成本估计为72％！此外，改进的精度引入了将该技术从人群研究扩展到单个受试者TEE的准确性评估的可能性。在第二阶段，LGR将继续与爱德华·梅兰森（Edward Melanson）教授和约翰·斯泰曼（John Speakman）教授一起演示并应用改进的仪器，以使用最小制备的人类尿液样品进行简单的同位素测量。将使用改进的三重同位素方法和结果测量与使用基于激光的同位素分析测量的代谢室中的TEE，标准DLW和标准DLW相比测量的结果。在该研究项目的结论中，LGR将证明使用TIWA在三异位DLW测量中使用，并紧急确定了TEE准确性的提高，并且由于使用17o/16o的背景波动的测量，DLW方法成本的降低。