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（T2 D）是由遗传和环境因素引起的，如饮食，以及 它们之间的复杂互动。虽然饮食是预防T2 D的基石，但饮食干预是 由于饮食评估技术和策略的局限性， 产生饮食变化。尽管努力减少SSB的消耗，SSB仍然是最大的单一来源 添加糖在美国SSB消费与T2 D和相关风险因素的风险较高有关， 但其潜在的生物学机制还不完全清楚。蛋白质组学分析和多组学 整合允许更详细表型分析，其可以提供饮食相关代谢的更广泛的观点 变化及其功能解释。检测血浆蛋白质组学和整合组学谱， 反映SSB摄入量和常见的替代饮料，人工增甜饮料（ASB），可能会提高 目前的饮食评估方法，并揭示了新的生物途径，将饮食与T2 D和相关风险联系起来 通过识别新的饮食生物标志物来确定这些因素。 SSB和ASB消耗的血浆蛋白质组学和多组学谱的发现具有巨大的意义。 提供对个体饮料摄入量的客观评估并使知情饮料 选择，这符合国家卫生研究所强调的精确营养方法。 (NIH)十年战略规划。该提案经济有效地利用了现有的蛋白质组学分析， 护士健康研究II和健康专业人员随访研究队列（n=648）。它还检查了重复的 在正在进行的NIH资助的首选方案替代试验（一项随机平行组6- 一项为期一个月的饮料试验，测试以ASB或水取代SSB对日常SSB消费者的影响。 我们将利用蛋白质组学和多组学网络和机器学习分析来识别歧视性 SSB和ASB消费水平之间的配置文件，并评估这些配置文件与T2 D的关联 危险因素核心假设是不同的蛋白质组学和组学图谱反映了习惯性SSB或ASB 摄入量及其组学生物标志物的变化与T2 D风险因素的变化相关，揭示了 饮料消耗的新生物标志物和通过饮料消耗改变的生物途径。这 K 01职业发展奖扩大了申请人在营养流行病学，组学和 生物统计学，以获得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 预防T2 D的应用。在著名的多学科研究团队的指导下， 申请人将获得必要的关键技能，以推进T2 D预防和完善的框架， 在互补的干预性和流行病学研究中利用创新的多组学技术 旨在为精准营养计划提供信息，并过渡到独立调查员。