The Interplay between Glucose Metabolism and Heat in Kidney Disease using a Metabolomics Approach

使用代谢组学方法研究肾脏疾病中葡萄糖代谢与热量之间的相互作用

• 批准号: 10429561
• 负责人: Roxana Cristina Chicas
• 金额: $ 14.83万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10429561
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Age; Agriculture; Aldosterone; Area; Automobile Driving; Awareness; Big Data Methods; Bioinformatics; Biological Markers; Biological Monitoring; Blood; Blood Glucose; Body Temperature; Body mass index; California; Cessation of life; Chronic; Chronic Kidney Failure; Clinical; Communities; Community Health; Complex; Creatinine; Data; Dehydration; Development; Diabetes Mellitus; Disease Progression; Doctor of Philosophy; Early Intervention; Environment; Fasting; Florida; Funding; Future; Generations; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Guatemala; Harvest; Health; Heart Rate; Heat Stress Disorders; Heat-Shock Proteins 90; Hispanic; Hispanic Populations; IL8 gene; Immigrant; Impairment; Industry; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-10; Interleukin-6; Intervention Trial; Investigation; Kidney; Kidney Diseases; Latina; Link; Longitudinal Studies; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic; Metabolic Pathway; Nephrology; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Nurses; Occupational; Pathway Analysis; Pathway interactions; Phenotype; Physiological; Plague; Plasma; Play; Population; Prediabetes syndrome; Prevalence; Proteinuria; Protocols documentation; Renal function; Research; Resolution; Risk; Risk Factors; Role; Sampling; Science; Scientist; Seasons; Serum; Signal Transduction; Subgroup; Symptoms; TNF gene; Temperature; Time; Training; United States National Institutes of Health; Uric Acid; Vulnerable Populations; Weather; Work; bilingualism; clinical phenotype; cohort; design; disorder risk; early detection biomarkers; farm worker; glucose metabolism; health care availability; health disparity; health equity; hot climate; kidney dysfunction; metabolic profile; metabolome; metabolomics; mortality; nephrogenesis; novel; population health; programs; recruit; renal damage; response; sex; success

PROJECT SUMMARY Roxana Chicas, PhD, RN is a 1st generation bilingual Latina and her goal is to become an independent NIH- funded nurse scientist developing a sustainable research program in the area of glucose metabolism and kidney disease. Support from the K23 award will provide the dedicated research time that will enable fundamental training and mentorship to further her understanding of: 1) the relationship of glucose metabolic pathways and heat exposure and the development of kidney disease in farmworkers using a metabolomics approach; and 2) the design and management of community-engaged intervention trials to decrease the risk of heat stress, renal dysfunction, and glucose dysregulation in vulnerable populations. Heat is the leading cause of weather-related deaths in the US, and farmworkers comprise an occupational sector particularly vulnerable to heat-related illness (HRI). Between 2-3 million workers in the US agricultural industry are at risk of heat related mortality at a rate that is 35 times greater than that of the general workforce population. In the last decade a number of investigations have shown a link between heat exposure and the risk of acute kidney injury (AKI). The chronic effects of the insidious and unexplained uptick of AKI among farmworkers, and the disproportionate burden of HRI and repetitive heat stress-induced dehydration are not well understood. The role that predisposing health conditions such as prediabetes may play in the risk of AKI has not been examined. While studies have documented heat-related risk factors and the body’s physiologic response to heat, few investigations have considered whether glucose metabolism and high environmental heat conditions are a risk factor for acute kidney injury, and less is known about the metabolic pathways underlying the body’s response to heat stress. The goal of this project is to characterize the physiologic phenotypes of farmworkers across seasons and exposures (indoors v. outdoors), using non-targeted, high-resolution metabolomics (HRM) to compare metabolomic profiles, and examine the associations between HRI clinical profiles (including core body temperature, heart rate, dehydration, HRI symptoms); inflammation biomarkers (IL-10, IL-6, IL-8, IL-1β, TNF-α, HSP72, HSP90); renal biomarkers (serum creatinine, BUN, eGFR, proteinuria, uric acid; aldosterone, and copeptin); and glucose clinical profiles (HbA1c, AM fasting blood glucose, and PM blood glucose levels). This proposed study will explore interplay of glucose metabolism and HRI and advance our understanding of the physiologic underpinnings of AKI and renal function. The incorporation of metabolomic profiles will add to the state of the science by indicating the underlying metabolic mechanisms and consequences of the physiologic response to heat stress.

项目摘要 ROXANA CHICAS，PHD，RN是第一代双语拉丁裔，她的目标是成为独立的NIH- 资助的护士科学家在该领域制定可持续研究计划 葡萄糖代谢和 肾脏疾病。 K23奖的支持将为专门的研究时间提供 基本培训和心态，以进一步了解她：1） 葡萄糖代谢 途径和热量暴露以及 使用代谢组学的农场工人中的肾脏疾病 方法; 2）社区参与干预试验的设计和管理，以降低 脆弱人群中的热应激，肾功能障碍和葡萄糖失调。热量是主要原因 美国与天气有关的死亡人数，农场工人组成一个占领部门特别脆弱 与热有关的疾病（HRI）。美国农业产业的2-3万工人面临着炎热的风险 相关死亡率的速度是一般劳动力人口的35倍。在最后 十年的许多调查显示了热暴露与急性肾脏的风险之间有联系 受伤（AKI）。 AKI在农场工人中的阴险和意外增长的慢性影响， HRI的不成比例的伯宁和重复的热应激引起的脱水尚不清楚。这 容易发生健康状况（例如糖尿病前期）可能在AKI风险中扮演的角色尚未 检查。研究记录了与热有关的危险因素以及人体对 热量，很少有人考虑葡萄糖代谢和高环境温度条件是否 是急性肾脏损伤的危险因素，对人体的代谢途径知之甚少 对热应力的反应。该项目的目的是表征农场工人的生理表型 在各个季节和曝光中（室内诉室外），使用非目标，高分辨率代谢组学（HRM） 比较代谢组谱并检查HRI临床轮廓之间的关联（包括核心 体温，心率，脱水，HRI症状）；炎症生物标志物（IL-10，IL-6，IL-8，IL-1β， TNF-α，HSP72，HSP90）;肾脏生物标志物（血清肌酐，BUN，EGFR，蛋白尿症，尿酸；醛固酮，醛固酮， 和copeptin）;和葡萄糖临床特征（HBA1C，AM AM AM空腹血糖和PM血糖水平）。 这项拟议的研究将探索葡萄糖代谢和HRI的相互作用，并提高我们对 AKI和肾功能的生理基础。代谢组概况的合并将添加到 科学的状态通过指出了基本的代谢机制和后果 对热应激的生理反应。