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: 10708153
• 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/10708153
• 关键词: Acclimatization; 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; Dedications; 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; 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.

项目概要 Roxana Chicas 博士、注册护士是第一代双语拉丁裔人士，她的目标是成为一名独立的 NIH- 资助护士发展科学家在该领域的可持续研究计划 葡萄糖代谢和 K23 奖项的支持将提供专门的研究时间，使之成为可能。 基础培训和指导，以帮助她进一步理解：1） 葡萄糖代谢 途径和热暴露以及发展 使用代谢组学研究农场工人的肾脏疾病 方法；2) 设计和管理社区参与的干预试验，以降低风险 热应激、功能障碍和易受影响的肾脏人群的葡萄糖失调是主要原因。 美国与天气相关的死亡人数，以及职业部门中的农场工人尤其脆弱 美国农业行业有 2-300 万名工人面临高温风险。 相关死亡率是过去一般劳动力人口的 35 倍。 十年来，多项研究表明热暴露与急性肾病风险之间存在联系 农场工人中 AKI 的隐匿性和不明原因的增加的慢性影响，以及 HRI 造成的不成比例的负担和重复性热应激引起的脱水尚不清楚。 糖尿病前期等诱发健康状况可能在 AKI 风险中发挥的作用尚未得到证实 研究已经记录了与热有关的危险因素和身体对热的生理反应。 热，很少有研究考虑葡萄糖代谢是否与高环境热条件有关 是急性肾损伤的危险因素，而人们对身体基础代谢途径知之甚少。 该项目的目标是描述农场工人的生理表型。 跨季节和暴露（室内与室外），使用非靶向、高分辨率代谢组学 (HRM) 比较代谢组学特征，并检查 HRI 临床特征之间的关联（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、尿酸；醛固酮、 和和肽素）；以及血糖临床特征（HbA1c、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，并加深我们对 AKI 和肾功能的生理基础将增加代谢组学特征。 通过指出潜在的代谢机制和后果来了解科学的现状 对热应激的生理反应。