Glycemic Variability and Fluctuations in Cognitive Status in Adults with Type 1 Diabetes

尽管有明确的科学和公共卫生相关性，但现实世界中血糖漂移对认知能力的影响 人们对成人1型糖尿病(T1D)的状况知之甚少。迫切需要确定血糖水平 T1D认知变异性的决定因素。我们的长期目标是提供以证据为基础的指导方针 监测成人T1D患者的认知状态并预防认知损害。我们的目标是 建议的研究是表征血糖漂移对T1D认知的影响，并确定 这一关系的调解人和调解人。这项工作是通过开发和提供 连续血糖监测仪(CGM)设备，可以提供关于血糖状态和转换的实时数据- 时间到了。我们的中心假设是血糖漂移(低血糖、高血糖和快速 成人T1D患者的血糖变化)与认知状态的波动有关。我们进一步 假设血糖相关的认知变异性受急性心理状态(压力、 消极情绪、疲劳)和慢性糖尿病相关因素(糖化血红蛋白、病程、并发症)。血糖升高 当认知资源耗尽(例如，由于压力)或 在那些由于糖尿病的不利神经影响而导致认知储备水平较低的人中。我们会 通过生态瞬间评估(EMA)和多个简短的日常客观认知来测试我们的假设 (加工速度、工作记忆和认知控制)和心理状态(压力、负面情绪、 对200名患有T1D的成年人同时进行Dexcom G6 CGM期间的疲劳)评估。我们利用这个机会 基于神经科学的自我管理认知测试，在移动设备上验证远程数据 收集。我们将通过以下具体目标完成这项工作：1)描述关系 血糖波动和认知状态之间的关系。我们预测，在过去的几年里，我们的认知表现会更差 低血糖、高血糖，以及当血糖迅速变化时。2)确定状态变量如何 (压力、消极情绪和疲劳)影响血糖和认知状态之间的关系。 我们预测，减少可用认知资源的时变因素(如压力、负面情绪、 疲劳)将解释(中介)或放大(适度)血糖和认知之间的关系 状态。3)确定糖尿病相关因素是否缓和了血糖和 认知状态。我们预测，糖尿病相关疾病因素将与更大的 由于认知资源的减少而导致的认知状态的血糖漂移。这项研究将使我们能够 确定血糖漂移如何影响认知，并确定其调节因子和调节因子 这种关系可能导致新的干预措施。这样的理解对于最大限度地提高日常工作效率是必要的。 日认知、功能状态和生活质量。它还将导致经验支持的自我管理 用于跟踪认知状态的工具，可快速转换为临床护理。

Despite clear scientific and public health pertinence, the real-world effects of glycemic excursions on cognitive status in adults with type 1 diabetes (T1D) are poorly understood. There is a critical need to identify glycemic determinants of cognitive variability in T1D. Our long-term goals are to provide evidence-based guidelines for monitoring cognitive status and preventing cognitive impairment in adults with T1D. Our objective for the proposed study is to characterize the impact of glycemic excursions on cognition in T1D and determine mediators and moderators of this relationship. This work is enabled by the development and availability of continuous glucose monitor (CGM) devices that can provide real-time data about glycemic status and change-over- time. Our central hypothesis is that glycemic excursions (hypoglycemia, hyperglycemia and rapid glycemic change) in adults with T1D are associated with fluctuations in cognitive status. We further hypothesize that glycemia-related cognitive variability is influenced by both acute psychological state (stress, negative affect, and fatigue) and chronic diabetes-related (HbA1c, duration, complications) factors. Glycemic excursions are expected to impact cognition more when cognitive resources are depleted (e.g. by stress) or among those with lower levels of cognitive reserve due to the adverse neurological effects of diabetes. We will test our hypotheses via ecological momentary assessment (EMA) with multiple brief daily objective cognitive (processing speed, working memory, and cognitive control) and psychological state (stress, negative affect, fatigue) assessments during concurrent blinded Dexcom G6 CGM, in 200 adults with T1D. We take advantage of neuroscience-based self-administered cognitive tests that are validated on mobile devices for remote data collection. We will accomplish this work through the following Specific Aims: 1) Characterize the relationship between glycemic excursions and cognitive status. We predict cognitive performance will be poorer during hypoglycemia, hyperglycemia, and when glucose is rapidly changing. 2) Determine how state variables (stress, negative affect, and fatigue) impact the relationship between glycemia and cognitive status. We predict that time-varying factors that reduce available cognitive resources (e.g. stress, negative affect, fatigue) will either explain (mediate) or amplify (moderate) the relationship between glycemia and cognitive status. 3) Determine if diabetes-related factors moderate the association between glycemia and cognitive status. We predict that diabetes-related disease factors will be associated with greater impact of glycemic excursions on cognitive status due to reductions in cognitive resources. This study will allow us to determine how glycemic excursions impact cognition, as well as to identify mediators and moderators of this relationship that could lead to novel interventions. Such an understanding will be necessary to maximize day-to- day cognition, functional status, and quality of life. It will also lead to an empirically supported self-management tool for tracking cognitive status that can be rapidly translated to clinical care.