Associations of Targeted Metabolites with Protein, Saturated Fat and Glucose Homeostasis

目标代谢物与蛋白质、饱和脂肪和葡萄糖稳态的关联

• 批准号: 10598088
• 负责人: MEGHANA DIPTI GADGIL
• 金额: $ 12.11万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598088
• 关键词: Adult; Affect; Animals; Award; Betaine; Biological Assay; Butter; California; Carbohydrates; Ceramides; Communication; Consumption; Crossover Design; Dairying; Data; Diabetes Mellitus; Diabetes prevention; Diet; Dietary Factors; Dietary Intervention; Dietary Proteins; Disease; Domestic Fowls; Dyslipidemias; Energy Intake; Fasting; Fatty acid glycerol esters; Funding; Glucose; Goals; Grant; Impairment; Incidence; Individual; Insulin; Insulin Resistance; Intake; Internal Medicine; Internist; Intervention; Investigation; Knowledge; Link; Lipids; Longitudinal Studies; Measurement; Measures; Meat; Mediating; Mentored Patient-Oriented Research Career Development Award; Metabolic; Metabolism; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Nutritional Study; OGTT; Participant; Physicians; Plant Proteins; Plants; Plasma; Positioning Attribute; Prevention; Processed Meats; Proteins; Public Health; Randomized; Randomized, Controlled Trials; Recommendation; Research Personnel; Risk; Risk Factors; Risk Marker; Role; Sampling; San Francisco; Source; Specific qualifier value; Sphingolipids; Thinness; Universities; Vegetables; Work; acylcarnitine; arm; biomarker identification; blood glucose regulation; cardiovascular health; career development; design; diabetes risk; dietary; epidemiology study; feeding; glycemic control; indexing; insight; insulin secretion; insulin sensitivity; metabolomics; mid-career faculty; modifiable risk; nutrition; observational cohort study; precision nutrition; prevent; programs; protein biomarkers; protein intake; randomized trial; red meat consumption; saturated fat; sugar; tool; trial design

PROJECT SUMMARY Current dietary guidance to prevent diabetes focuses on minimizing intake of added sugars and refined carbohydrates and promoting non-starchy vegetable consumption. Evidence and communication regarding the impact of protein type and intake of saturated fat on diabetes risk is less clear. An examination of controlled diet intake, changes in metabolism and subsequent glucose homeostasis will clarify and isolate the effect of protein source and amount of saturated fat on short and long-term indicators of diabetes risk. The concurrent work on my K23 proposal “Prevention of Type 2 Diabetes with Diet and Metabolomics” uses untargeted metabolomics data to characterize a metabolite profile of a high-quality diet and determine associations with incident diabetes in the context of large, well-characterized observational cohort studies. In order to build on these findings, the objective of this proposal is to evaluate the associations of source of protein (red meat, white meat and plant-based) and level of saturated fat (high and low) with targeted and specific classes of metabolites and with markers of glucose homeostasis in the context of a controlled diet intervention. This proposal will leverage data and biospecimens from the completed Animal and Plant Protein and Cardiovascular Health” (APPROACH) (PI: Krauss) trial, which originally investigated changes in atherogenic dyslipidemia according to protein source and level of saturated fat. Aim 1 will evaluate the effect of lean sources of red meat, white poultry meat and plant-based protein on circulating acylcarnitines and measures of glucose and insulin sensitivity, secretion and the disposition index (DI). Aim 2 will evaluate level of saturated fat generated from butter and high-fat dairy on circulating sphingolipids, including ceramides, and the same measures of glucose and insulin action. Each aim will examine the extent to which these specified circulating metabolites mediate the association of diet intake and measures of glucose homeostasis. The candidate for this Small Grant Program for NIDDK K23 Recipients, Dr. Meghana Gadgil, is a General Internist and an Associate Professor in the Division of General Internal Medicine at the University of California, San Francisco. Dr. Gadgil is a physician-investigator in her final year of a 3-year K23 award from NIDDK, with a strong background in nutrition and diabetes and current work examining the role of metabolomics in these topics. This proposal will reinforce and extend the knowledge gained during the career development period, and will lead to an independent award investigating changes in protein source and saturated fat based on metabolite profile for individuals at risk for diabetes. This study is relevant and timely, as the incidence of both diabetes and its risk factors continues to rise and further refinement of public health dietary guidance to prevent diabetes is needed. The proposed investigations will contribute understanding, new knowledge, and potential targets of dietary intervention for diabetes prevention.

项目概要 目前预防糖尿病的饮食指南的目标是添加糖和精制糖的摄入量 碳水化合物和促进非淀粉类蔬菜消费的证据和沟通。 蛋白质类型和饱和脂肪摄入量对糖尿病风险的影响尚不清楚。 饮食摄入、新陈代谢的变化以及随后的葡萄糖稳态将澄清和分离的影响 蛋白质来源和饱和脂肪含量对糖尿病风险的短期和长期指标的影响。 我的 K23 提案“通过饮食和代谢组学预防 2 型糖尿病”的工作使用了非针对性的方法 代谢组学数据来表征高质量饮食的代谢物谱并确定与 大型、特征明确的观察性队列研究背景下的糖尿病事件。 这些发现，该提案的目的是评估蛋白质来源（红肉、 白肉和植物性肉类）和饱和脂肪水平（高和低）以及有针对性和特定类别的 在控制饮食干预的情况下，代谢物和葡萄糖稳态标志物。 该提案将利用来自已完成的动物和植物蛋白质和 心血管健康”（APPROACH）（PI：Krauss）试验，最初研究了致动脉粥样硬化的变化 血脂异常根据蛋白质来源和饱和脂肪水平评估瘦肉的效果。 红肉、白禽肉和植物蛋白的来源对循环酰基肉碱的影响及措施 葡萄糖和胰岛素敏感性、分泌和处置指数 (DI) 将评估饱和脂肪水平。 由黄油和高脂乳制品中的循环鞘脂（包括神经酰胺）产生 每个目标都将检查这些特定循环的程度。 代谢物介导饮食摄入和葡萄糖稳态测量的关联。 NIDDK K23 受助人小额赠款计划的候选人 Meghana Gadgil 博士是一名将军 加州大学普通内科内科医生和副教授， 旧金山，Gadgil 博士是一名医师研究员，正在获得 NIDDK 为期 3 年的 K23 奖的最后一年， 在营养和糖尿病方面拥有深厚的背景，目前正在研究代谢组学在这些方面的作用 该提案将加强和扩展职业发展期间获得的知识， 并将获得一项独立奖项，调查蛋白质来源和饱和脂肪的变化 鉴于这两种疾病的发病率，这项研究是相关且及时的。 糖尿病及其危险因素持续上升，公共卫生膳食指南进一步细化 预防糖尿病是必要的，拟议的研究将有助于理解、新知识和 预防糖尿病的饮食干预的潜在目标。