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

项目摘要 目前预防糖尿病的饮食指导重点是尽量减少添加糖和精制糖的摄入。 碳水化合物和促进非淀粉蔬菜消费。关于《公约》的证据和来文 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。检查控制 饮食摄入，代谢和随后的葡萄糖稳态的变化将澄清和隔离的影响， 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。并发 我的K23提案“饮食和代谢组学预防2型糖尿病”的工作使用了非靶向的 代谢组学数据来表征高质量饮食的代谢物谱，并确定与 在大型、特征良好的观察性队列研究的背景下发生糖尿病。为了巩固 根据这些发现，本建议的目的是评估蛋白质来源（红肉， 白色肉和植物性）和饱和脂肪水平（高和低）， 代谢物和葡萄糖稳态的标志物在控制饮食干预的情况下。这 该提案将利用已完成的动植物蛋白的数据和生物标本， 心血管健康”（APPROACH）（PI：Krauss）试验，该试验最初研究了动脉粥样硬化的变化， 根据蛋白质来源和饱和脂肪水平的血脂异常。目标1将评估精益生产的效果 红肉、白色禽肉和植物性蛋白质来源对循环中酰基肉毒碱的影响， 葡萄糖和胰岛素敏感性、分泌和处置指数（DI）。目标2将评估饱和脂肪的水平 从黄油和高脂乳制品中产生的对循环鞘脂，包括神经酰胺的影响， 葡萄糖和胰岛素作用的测量。每个目标都将检查这些特定的循环 代谢物介导饮食摄入和葡萄糖稳态测量的关联。 NIDDK K23接受者小额赠款计划的候选人Meghana Gadgil博士是一名将军， 加州大学普通内科的内科医生和副教授， 旧金山弗朗西斯科。Gadgil博士是NIDDK 3年K23奖的最后一年的医生调查员， 在营养和糖尿病方面有很强的背景，目前正在研究代谢组学在这些方面的作用。 话题这项建议将加强和扩大在职业发展期间获得的知识， 并将导致一个独立的奖项，调查蛋白质来源和饱和脂肪的变化， 代谢物谱的个体在糖尿病的风险。这项研究是相关和及时的，因为两者的发病率 糖尿病及其危险因素继续上升，进一步完善公共卫生饮食指导， 预防糖尿病是必要的。拟议的调查将有助于理解，新的知识， 预防糖尿病的饮食干预的潜在目标。

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.