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

点击翻译按钮获取中文摘要

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.