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.

项目概要： 2 型糖尿病 (T2D) 是由遗传和环境因素（例如饮食）以及饮食习惯引起的。 它们之间存在复杂的相互作用。虽然饮食是预防 T2D 的基石，但饮食干预才是预防 T2D 的基础。 由于饮食评估技术和策略的限制，通常难以实施和监测 尽管努力减少 SSB 的消费，但 SSB 仍然是最大的单一来源。 美国的 SSB 消费量与 T2D 和相关风险因素的较高风险有关， 但潜在的生物学机制尚未完全了解。 整合允许更详细的表型分析，这可以提供更广泛的饮食相关代谢视图 血浆蛋白质组学和综合组学概况的检查。 反映了 SSB 的摄入量，而一种常见的替代饮料——人工甜味饮料 (ASB) 可能会增强 当前的饮食评估方法，并揭示将饮食与 T2D 及相关风险联系起来的新生物途径 通过识别新型饮食生物标志物来确定因素。 SSB 和 ASB 消耗的血浆蛋白质组学和多组学特征的发现具有巨大意义 能够对个人饮料摄入量进行客观评估并实现知情饮料 选择，这符合美国国立卫生研究院强调的精准营养方法 (NIH) 10 年战略计划。该提案经济有效地利用了现有的蛋白质组学分析。 它还对护士健康研究 II 和卫生专业人员随访研究队列 (n=648) 进行了重复检查。 NIH 资助的 SUBstituting with Preferred OPtions 试验正在进行中，这是一项随机平行臂 6- 为期一个月的饮料试验，测试日常 SSB 消费者中用 ASB 或水替代 SSB 的效果。 我们将利用蛋白质组学和多组学网络以及机器学习分析来识别歧视性 SSB 和 ASB 消耗水平之间的概况，并评估这些概况与 T2D 的关联 核心假设是不同的蛋白质组学和组学特征反映了习惯性的 SSB 或 ASB。 摄入量以及组学生物标志物的变化与 T2D 危险因素的变化相关，揭示 饮料消费的新生物标志物和饮料消费改变的生物途径。 K01 职业发展奖扩展了申请人在营养流行病学、组学和 生物统计学，以熟练掌握干预研究的设计和管理、实施 尖端的多组学统计分析技术和精准营养的科学领导力 在著名的多学科研究团队的指导下，T2D 预防的应用。 申请人将获得推进 T2D 预防和完善 T2D 框架所需的关键技能 多组学技术在补充介入和流行病学研究中的创新利用 旨在为精准营养计划提供信息并过渡到独立研究者。