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标准标志物（空腹血糖和糖化血红蛋白）对长期预后的价值，在一个大型代表性队列中，从中年到老年随访25年。目的是：1)评估新的血糖指标对已知指标的附加预后价值，以确定微血管和大血管结局高危人群和亚群；2)探讨血糖指标与健康结局相关性的种族和年龄相关差异；3)开展新的血糖标志物全基因组关联研究，寻找葡萄糖代谢的重要易感基因；4)表征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系。设计和方法：我们将分析储存的标本，并利用社区动脉粥样硬化风险研究（ARIC）的数据，这是一项正在进行的nhlbi资助的社区流行病学队列，约15,000名黑人和白人成年人，随访25年。拟议的研究将建立在父母研究的现有基础上，并利用参与者生命中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）。主要关注的结局是微血管疾病（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。意义：如果我们证明新的血糖指标能提供额外的预后信息，我们的结果将提示这些指标在临床实践中的实用性。这样的结果将挑战糖尿病的定义。我们还将证明记录的种族差异和年龄相关的血糖水平差异是否具有临床重要性。我们对共同遗传决定因素的研究将揭示糖尿病生物学和葡萄糖代谢促进并发症发展的机制。如果这个项目成功，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。

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.