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

项目总结 目前预防糖尿病的饮食指南侧重于最大限度地减少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。证据和通讯关于 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。对受控对象的审查 饮食摄入量、新陈代谢的变化和随后的葡萄糖稳态将澄清和分离 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。同时发生的 我的K23提案《通过饮食和代谢组学预防2型糖尿病》的工作使用了无针对性的 代谢组学数据，以表征高质量饮食的代谢物概况，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。为了在此基础上继续发展 这些发现，这项建议的目的是评估蛋白质来源(红肉， 白肉和植物性)和饱和脂肪水平(高和低)，有针对性的和特定的类别 在控制饮食干预的背景下，代谢物和葡萄糖动态平衡的标志物。这 提案将利用来自完整的动物和植物蛋白和 心血管健康“(Approach)(PI：Krauss)试验，最初调查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而定。目标1将评估精益的效果 红肉、白禽肉和植物蛋白在循环中的来源和措施 血糖和胰岛素敏感性、分泌和处置指数(DI)。目标2将评估饱和脂肪水平 从黄油和高脂肪乳制品中产生的对包括神经酰胺在内的循环神经鞘脂脂的影响 测量葡萄糖和胰岛素的作用。每个目标都将检查这些指定循环的程度 代谢产物调节饮食摄入量和葡萄糖动态平衡的测量之间的关系。 这项面向NIDDK K23获奖者的小额赠款计划的候选人Meghana Gadgil博士是一名将军 他是加州大学普通内科内科的内科医生和副教授， 旧金山。Gadgil博士是NIDDK颁发的为期3年的K23奖项的最后一年的医生兼研究员， 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 主题。这项提议将加强和扩展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 糖尿病高危人群的代谢物概况。这项研究是相关和及时的，因为这两种情况的发生 糖尿病及其危险因素持续上升和进一步细化公众健康饮食指导 预防糖尿病是必要的。拟议的调查将有助于理解、新的知识和 饮食干预预防糖尿病的潜在靶点。

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.