Comparative Epidemiology for Emerging Glycemic Markers

描述（由申请人提供）：本项目将在一个从中年到老年随访25年的大型代表性队列中，评价替代血糖标志物是否为标准标志物（空腹血糖和HbA 1c）的长期预后增加价值。其目标是：1）评估新的血糖标志物对识别微血管和大血管结局高风险人群和亚组的已知指标的附加预后价值; 2）调查血糖标志物与健康结局相关性的种族和年龄相关差异; 3）进行新的血糖标志物的全基因组关联研究，以识别在葡萄糖代谢中重要的易感基因;以及4）描述低血糖和高血糖状态与老年人虚弱、情绪、身体和认知障碍以及痴呆风险的关联。设计和方法：我们将分析储存的标本，并利用来自社区动脉粥样硬化风险（ARIC）研究的数据，ARIC研究是一项由NHLBI资助的基于社区的流行病学队列研究，对约15，000名黑人和白色成年人进行了25年的随访。拟议的研究将建立在母研究的现有基础设施上，并利用参与者生命周期两个阶段获得的血液样本：中年（1990-92，48-68岁）和老年（2011-2013，69-89岁）。关注的主要结局是微血管疾病（肾脏和视网膜疾病）、大血管（心血管）疾病、虚弱、情绪、身体和认知障碍、痴呆和全因死亡率。重要性：如果我们证明，新的标记物的乳腺癌提供额外的预后信息，我们的研究结果将表明这些措施在临床实践中的效用。这些结果将挑战糖尿病的定义。我们还将证明是否记录种族差异和年龄相关的差异水平的糖尿病是临床重要的。我们对常见遗传决定因素的研究将揭示糖尿病的生物学和葡萄糖代谢促进并发症发展的机制。如果该项目成功，我们的研究结果将与临床实践直接相关，并为预防糖尿病及其并发症的策略提供信息。 公共卫生相关性：本项目将比较葡萄糖代谢的替代标志物与当前临床指标（空腹血糖、血红蛋白A1 c）的有效性。我们将评估这些标志物是否可以改善健康结果的预测。我们还将调查糖尿病风险中与种族和年龄相关的差异，并描述遗传相关性，以了解糖尿病的生物学。我们的研究结果应该有助于预防糖尿病及其并发症。

DESCRIPTION (provided by applicant): This project will evaluate whether alternative glycemic markers add value to standard markers (fasting glucose and HbA1c) for long-term prognosis across a wide range of outcomes in a large representative cohort followed for 25-years from midlife to older age. The aims are: 1) To assess the added prognostic value of novel glycemic markers to known measures for identifying populations and subgroups at high risk for microvascular and macrovascular outcomes; 2) To investigate racial- and age-related differences in the associations of glycemic markers with health outcomes; 3) To conduct a genome-wide association study of new glycemic markers to identify susceptibility genes important in glucose metabolism; and 4) To characterize the associations of hypo- and hyper-glycemic states with frailty, mood, and physical and cognitive impairment and dementia risk in the elderly. Design and Methods: We will analyze stored specimens and utilize data from the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing NHLBI-funded community-based epidemiologic cohort of ~15,000 black and white adults followed for 25 years. The proposed research will build on the existing infrastructure of the parent study and utilize blood samples obtained during two phases of the participants' lifespan: during midlife (1990-92, 48-68 years old) and old age (2011-2013, 69-89 years old). The main outcomes of interest are microvascular disease (kidney and retinal disease), macrovascular (cardiovascular) disease, frailty, mood, physical and cognitive impairment, dementia, and all-cause mortality. Significance: If we demonstrate that novel markers of glycemia contribute additional prognostic information, our results will suggest the utility of these measures in clinical practice. Such results would challenge the definition of diabetes. We will also demonstrate whether documented racial disparities and age-related differences in levels of glycemia are clinically important. Our investigation of common genetic determinants will shed light on the biology of diabetes and the mechanisms by which glucose metabolism contributes to the development of complications. If this project is successful, our results will have direct relevance to clinical practice and inform strategies for the prevention of diabetes and its complications. PUBLIC HEALTH RELEVANCE: This project will compare the effectiveness of alternative markers of glucose metabolism to current clinical measures (fasting glucose, hemoglobin A1c). We will assess whether these markers can improve prediction of health outcomes. We will also investigate racial and age-related disparities in diabetes risk and characterize genetic associations to inform the biology of diabetes. Our results should help prevent diabetes and its complications.