Proteomic and integrative omic profiles of sugar- and artificially sweetened beverage consumption and changes in type 2 diabetes risk factors

糖和人工甜味剂饮料消费的蛋白质组学和综合组学特征以及 2 型糖尿病危险因素的变化

• 批准号: 10723200
• 负责人: Danielle Haslam
• 金额: $ 15.97万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723200
• 关键词: Address; Adherence; American; Beverages; Biological; Biological Assay; Biological Markers; Biometry; Body Weight; Calibration; Calories; Cardiometabolic Disease; Clinical; Cohort Studies; Complement; Complex; Consumption; Data; Development Plans; Diabetes Mellitus; Diabetes prevention; Diet; Diet Monitoring; Dietary Assessment; Dietary Intervention; Dietary intake; Disease; Effectiveness; Ensure; Environment; Environmental Risk Factor; Epidemiology; Follow-Up Studies; Foundations; Funding; Genetic; Goals; Health Professional; Healthcare Systems; Individual; Inflammation; Intake; Interdisciplinary Study; Intervention Studies; Intervention Trial; K-Series Research Career Programs; Leadership; Life Style; Link; Lipids; Longevity; Machine Learning; Measures; Mentorship; Metabolic; Methods; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Network-based; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Obesity; Participant; Pathway interactions; Patient Self-Report; Pattern; Phenotype; Plasma; Plasma Proteins; Prevention; Prevention strategy; Proteomics; Quality of life; Randomized; Randomized, Controlled Trials; Reporting; Research; Research Design; Research Personnel; Risk Factors; Sampling; Scientist; Solid; Source; Statistical Data Interpretation; Strategic Planning; Sugar Substitute; Techniques; Technology; Testing; Training; United States; United States National Institutes of Health; Validation; Water; arm; biomarker discovery; biomarker identification; career; career development; clinical translation; cost; design; dietary; disorder risk; epidemiology study; experience; gut microbiome; high risk; improved; innovation; lifestyle intervention; multiple omics; notch protein; novel; novel marker; nutritional epidemiology; population based; precision nutrition; prevent; protein biomarkers; protein metabolite; response; screening; skills; success; sugar; sweetened beverage; tool; treatment strategy

PROJECT SUMMARY: Type 2 diabetes (T2D) is caused both by genetic and environmental factors, such as diet, as well as the complex interactions between them. While diet is the cornerstone for T2D prevention, dietary interventions are often difficult to implement and monitor due to limitations in dietary assessment techniques and strategies to produce dietary changes. Despite efforts to reduce SSB consumption, SSBs remain the largest single source of added sugar in the US. SSB consumption has been linked to a higher risk of T2D and related risk factors, but the underlying biological mechanisms are not completely understood. Proteomic profiling and multi-omic integration allow for more detailed phenotyping that may provide a broader view of diet-associated metabolic changes and their functional interpretation. Examination of plasma proteomic and integrative omic profiles that reflect SSB intake and a common alternative beverage, artificially sweetened beverages (ASB), may enhance current dietary assessment methods and unveil novel biological pathways linking diet to T2D and related risk factors through identification of novel dietary biomarkers. Discovery of plasma proteomic and multi-omic profiles of SSB and ASB consumption has immense potential to provide an objective assessment of individual beverage intake and enable informed beverage choices, which is in line with the precision nutrition approaches emphasized in the National Institute of Health’s (NIH) 10-year strategic plan. This proposal cost-effectively leverages existing proteomics profiling among the Nurses’ Health Study II and Health Professionals Follow-up Study cohorts (n=648). It also examines repeated assays in the ongoing NIH-funded SUBstituting with Preferred OPtions trial, a randomized parallel-arm 6- month beverage trial testing the effects of substituting SSBs with ASB or water among daily SSB consumers. We will utilize proteomic and multi-omic network and machine learning analyses to identify discriminatory profiles between SSB and ASB consumption levels and evaluate the associations of these profiles with T2D risk factors. The central hypothesis is that distinct proteomic and omic profiles reflect habitual SSB or ASB intake and that changes in their omic biomarkers are associated with changes in T2D risk factors, revealing novel biomarkers of beverage consumption and biological pathways modified by beverage consumption. This K01 career development award expands on the applicant’s experience in nutritional epidemiology, omics, and biostatistics to gain proficiency in the design and management of intervention studies, implementation of cutting-edge multi-omic statistical analysis techniques, and scientific leadership for precision nutrition applications for T2D prevention. With mentorship from a renowned multidisciplinary research team, the applicant will gain the crucial skills necessary to advance T2D prevention and refine a framework for the utilization of innovative multi-omics techniques in complementary interventional and epidemiological study designs to inform precision nutrition initiatives and transition to an independent investigator.

项目摘要： 2型糖尿病（T2D）是由遗传和环境因素（例如饮食）以及 它们之间的复杂互动。饮食是预防T2D的基石，但饮食干预措施是 由于饮食评估技术和策略的限制，通常难以实施和监控 产生饮食变化。尽管努力减少SSB消耗，但SSB仍然是最大的单一来源 在美国添加的糖。 SSB的消费与T2D和相关风险因素的较高风险有关， 但是，基本的生物学机制尚未完全理解。蛋白质组学分析和多运动 整合允许更详细的表型，可以为饮食相关代谢提供更广泛的视野 变化及其功能解释。检查血浆蛋白质组学和综合元素特征 反射SSB的摄入量和常见的替代床，人为甜味床（ASB）可能会增强 当前的饮食评估方法和揭露新的新型生物学途径，将饮食与T2D联系起来及其相关风险 通过鉴定新型饮食生物标志物的因素。 SSB和ASB消耗的等离子体蛋白质组学和多矩轮廓的发现巨大 提供对单个贝德摄入量的客观评估的潜力，并启用知情的床位 选择，这符合美国国家卫生研究院强调的精确营养方法 （NIH）十年战略计划。该提议具有成本效益的利用 护士健康研究II和卫生专业人员随访研究队列（n = 648）。它还检查重复 通过首选期权试验进行的NIH资助替代的测定，一个随机平行臂6-- 在每日SSB消费者中，用ASB或水代替SSB的月份试验测试SSB的效果。 我们将利用蛋白质组学和多摩变网络和机器学习分析来识别歧视性 SSB和ASB消耗水平之间的轮廓，并评估这些概况与T2D的关联 风险因素。中心假设是独特的蛋白质组学和泥土曲线反映了惯常的SSB或ASB 摄入量以及其OMIC生物标志物的变化与T2D风险因素的变化有关，揭示了 血液消耗和生物途径的新型生物标志物通过血液消耗修饰。这 K01职业发展奖扩展了申请人在营养流行病学，OMIC和 生物统计学以提高干预研究的设计和管理，实施 尖端的多族统计分析技术和精确营养的科学领导 预防T2D的申请。凭借著名的多学科研究团队的精神训练， 申请人将获得提高T2D预防并完善框架的至关重要技能 在完整的介入和流行病学研究中利用创新的多词技术 设计以告知精确营养计划，并过渡到独立研究者。