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，血糖波动对认知功能的现实影响， 成人1型糖尿病（T1 D）的发病情况尚不清楚。迫切需要确定血糖 T1 D认知变异的决定因素。我们的长期目标是提供基于证据的指南， 监测T1 D成人的认知状态并预防认知障碍。我们的目标是 拟议的研究是描述血糖波动对T1 D认知的影响，并确定 调解人和调解人的关系。这项工作是通过开发和提供 持续葡萄糖监测仪（CGM）设备，可提供有关血糖状态和转换的实时数据， 时间我们的中心假设是，血糖波动（低血糖、高血糖和快速血糖）可能是一个重要的因素。 血糖变化）与认知状态的波动有关。我们进一步 假设糖尿病相关认知变异性受急性心理状态（压力， 负面影响和疲劳）和慢性糖尿病相关（HbA 1c、病程、并发症）因素。血糖 当认知资源耗尽（例如，压力）时，预计短途旅行对认知的影响更大，或者 在那些由于糖尿病的不良神经影响而认知储备水平较低的人中。我们将 通过生态瞬时评估（EMA）测试我们的假设， （处理速度，工作记忆和认知控制）和心理状态（压力，负面影响， 疲劳）评估。我们利用 在移动的设备上验证远程数据的基于神经科学的自我管理认知测试 收藏.我们将通过以下具体目标来完成这项工作：1）描述关系 血糖波动和认知状态之间的联系我们预测认知能力会更差 低血糖症、高血糖症和血糖快速变化时。2)确定状态变量 （压力，负面影响和疲劳）影响情绪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（例如压力，负面影响， 疲劳）将解释（调解）或放大（适度）之间的关系， status. 3)确定糖尿病相关因素是否会调节糖尿病与糖尿病之间的关联。 认知状态我们预测，糖尿病相关疾病因素将与更大的影响， 由于认知资源减少，血糖波动对认知状态的影响。这项研究将使我们能够 确定血糖波动如何影响认知，以及确定这种影响的介质和调节剂。 这种关系可能导致新的干预措施。这样的理解将是必要的，以最大限度地提高日常- 日常认知、功能状态和生活质量。这也将导致一个经验支持的自我管理 用于跟踪认知状态的工具，可以快速转化为临床护理。

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.