The Role of Nontraditional Glycemic Markers in Diabetes and Albuminuria

描述(申请人提供)：糖尿病是一种慢性疾病，与微血管并发症的风险增加有关。在美国，13%的成年人患有糖尿病，另外30%的成年人患糖尿病的风险很高。非传统的血糖标志物糖化白蛋白(GA)、果糖胺和1，5-脱水葡萄糖醇(1，5-AG)可提供额外的预后信息，以确定糖尿病和微血管并发症的高危个体。GA、果糖胺和1，5-AG反映短期高血糖，并已被证明具有生理效应，包括启动信号通路，这些信号通路在糖尿病微血管并发症的发展中起活跃作用。此外，据报道，GA、果糖胺和1，5-AG水平存在重要的种族差异，在患有和不患有糖尿病的人中，非裔美国人的GA和果糖胺水平高于白人，而1，5-AG水平低于白人。本研究项目的目的是：1)评估GA、果糖胺和1，5-AG与糖尿病的相关性；2)评估GA、果糖胺和1，5-AG与普遍和偶发性蛋白尿的相关性；3)评估GA、果糖胺和1，5-AG与糖尿病和蛋白尿相关性的种族差异。为了达到这些目标，这项研究建议使用青年冠状动脉风险发展(CARDIA)研究的存储样本来测量GA、果糖胺和1，5-AG，并建立在这项前瞻性队列研究的现有基础上，该研究具有广泛的社会人口统计学、生活方式和临床变量集合。这项研究的发现可能被用来改善风险分层，并为开发新的治疗目标来预防糖尿病和微血管并发症提供信息。这项研究项目也将有助于帮助候选人在血糖标志物和代谢组学与糖尿病并发症的关系方面获得专业知识，以建立研究独立性。为了促进候选人的研究培训和职业发展，建议在以下方面开展具体的培训活动：1)糖尿病和肾脏病理生理学；2)风险预测方面的高级统计方法；3)代谢组学；以及4)研究招募、数据收集和研究管理，这将促进候选人向独立研究人员的转变。总而言之，这项有指导意义的研究科学家发展奖将通过提供获得血糖标志物和代谢组学及其对糖尿病和蛋白尿风险的影响的专业知识的机会，促进候选人作为独立科学家的职业发展。

DESCRIPTION (provided by applicant): Diabetes is a chronic disease associated with an increased risk of microvascular complications. In the United States, 13% of adults have diabetes and an additional 30% of adults are at high risk of developing diabetes. Nontraditional glycemic markers glycated albumin (GA), fructosamine, and 1,5-anhydroglucitol (1,5-AG)) may provide additional prognostic information to identify individuals at high risk of developing diabetes and microvascular complications. GA, fructosamine, and 1,5-AG reflect short-term hyperglycemia and have been shown to exhibit physiologic effects, including the initiation of signaling pathways, that are active in the development of diabetes microvascular complications. Moreover, important racial differences in GA, fructosamine, and 1,5-AG levels have been reported with African-Americans having higher GA and fructosamine and lower 1,5-AG levels than whites among individuals with and without diabetes. The aims of this research project are: 1) to evaluate the association of GA, fructosamine, and 1,5-AG with incident diabetes; 2) to evaluate the association of GA, fructosamine, and 1,5-AG with prevalent and incident albuminuria; and 3) to evaluate racial differences in the association of GA, fructosamine, and 1,5-AG with diabetes and albuminuria. To address these aims, this study proposes to measure GA, fructosamine, and 1,5- AG using stored specimens from the Coronary Artery Risk Development in Young Adults (CARDIA) Study and build upon the existing infrastructure of this prospective cohort study that has an extensive collection of socio- demographic, lifestyle, and clinical variables. The findings from this study may be used to improve risk stratification and inform the development of new therapeutic targets to prevent diabetes and microvascular complications. This research project will also be instrumental in helping the candidate gain expertise in the relation of glycemic markers and metabolomics with diabetes complications for establishing research independence. To foster the candidate's research training and career development, specific training activities are proposed in: 1) diabetes and renal pathophysiology; 2) advanced statistical methods in risk prediction; 3) metabolomics; and 4) research recruitment, data collection, and study management which will facilitate the candidate's transition to an independent investigator. In summary, this Mentored Research Scientist Development Award will foster the candidate's professional development as an independent scientist by providing an opportunity to gain expertise in glycemic markers and metabolomics and their effects on diabetes and albuminuria risk.