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

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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.