The Role of Nontraditional Glycemic Markers in Diabetes and Albuminuria

描述（由申请人提供）：糖尿病是一种与微血管并发症风险增加相关的慢性疾病。在美国，13%的成年人患有糖尿病，另外30%的成年人有患糖尿病的高风险。非传统的血糖标志物糖化白蛋白（GA）、果糖胺和1,5-无氢葡萄糖醇（1,5- ag）)可以提供额外的预后信息，以识别糖尿病和微血管并发症的高风险个体。GA、果糖胺和1,5- ag反映了短期高血糖，并显示出生理效应，包括信号通路的启动，这些信号通路在糖尿病微血管并发症的发展中很活跃。此外，GA、果糖胺和1,5- ag水平的重要种族差异已被报道，非洲裔美国人在有和没有糖尿病的白人中GA和果糖胺较高，1,5- ag水平较低。本研究的目的是：1)评估GA、果糖胺和1,5- ag与糖尿病发病的关系；2)评估GA、果糖胺和1,5- ag与蛋白尿流行和发生率的关系；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。为了实现这些目标，本研究建议使用来自年轻人冠状动脉风险发展（CARDIA）研究的存储标本来测量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设施上，该研究广泛收集了社会人口统计学、生活方式和临床变量。本研究结果可用于改善风险分层，并为开发新的治疗靶点提供信息，以预防糖尿病和微血管并发症。该研究项目也将有助于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，从而建立研究独立性。为了促进候选人的研究训练和职业发展，具体的训练活动建议：1)糖尿病和肾脏病理生理学；2)采用先进的统计方法进行风险预测；3)代谢组学;4)研究招募，数据收集和研究管理，这将有助于候选人过渡到独立研究者。总而言之，该导师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影响的专业知识的机会，促进候选人作为独立科学家的专业发展。

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.