Comparative Epidemiology for Emerging Glycemic Markers

描述(由申请人提供)：该项目将评估替代血糖标志物是否增加了标准标志物(空腹血糖和糖化血红蛋白)对长期预后的价值，对从中年到老年的大型代表性队列进行了25年的跟踪调查。其目的是：1)评估新的血糖标志物对确定微血管和大血管结果的高风险人群和亚群的已知措施的额外预后价值；2)调查血糖标志物与健康结果之间的种族和年龄相关的差异；3)对新的血糖标志物进行全基因组相关性研究，以确定在葡萄糖代谢中重要的易感基因；以及4)表征老年人中低血糖和高血糖状态与虚弱、情绪、身体和认知障碍以及痴呆症风险的关系。设计和方法：我们将分析存储的样本，并利用社区动脉粥样硬化风险(ARIC)研究的数据，这是一项由NHLBI资助的社区流行病学队列研究，对大约15,000名黑人和白人成年人进行了25年的跟踪调查。拟议的研究将建立在家长研究现有基础设施的基础上，并利用参与者生命的两个阶段获得的血液样本：中年(1990-92年，48-68岁)和老年(2011-2013年，69-89岁)。令人感兴趣的主要结果是微血管疾病(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、痴呆症和全因死亡。意义：如果我们证明新的血糖标志物有助于提供更多的预后信息，我们的结果将表明这些措施在临床实践中的实用性。这样的结果将挑战糖尿病的定义。我们还将证明记录在案的种族差异和与年龄相关的血糖水平差异是否具有临床重要性。我们对常见遗传决定因素的研究将有助于阐明糖尿病的生物学以及葡萄糖代谢促进并发症发生的机制。如果该项目成功，我们的结果将直接与临床实践相关，并为预防糖尿病及其并发症的战略提供参考。 公共卫生相关性：该项目将比较糖代谢替代标记物与当前临床措施(空腹血糖、血红蛋白A1c)的有效性。我们将评估这些标记物是否可以改善对健康结果的预测。我们还将调查糖尿病风险中与种族和年龄相关的差异，并确定基因关联的特征，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.