Despite associations between hypoglycemia and cognitive performance using cross-sectional and experimental methods (e.g., Insulin clamp studies), few studies have evaluated this relationship in a naturalistic setting. This pilot study utilizes an EMA study design in adults with T1D to examine the impact of hypoglycemia and hyperglycemia, measured using CGM, on cognitive performance, measured via ambulatory assessment.

Twenty adults with T1D (mean age 38.9 years, range 26-67; 55% female; 55% bachelor’s degree or higher; mean HbA1c = 8.3%, range 5.4% - 12.5%), were recruited from the Joslin Diabetes Center at SUNY Upstate Medical University. A blinded Dexcom G6 CGM was worn during everyday activities while completing 3-6 daily EMAs using personal smartphones. EMAs were delivered between 9 am and 9 pm, for 15 days. EMAs included 3 brief cognitive tests developed by testmybrain.org and validated for brief mobile administration (Gradual Onset CPT d-prime, Digit Symbol Matching median reaction time, Multiple Object Tracking percent accuracy) and self-reported momentary negative affect. Day-level average scores were calculated for the cognitive and negative affect measures. Hypoglycemia and hyperglycemia were defined as the percentage of time spent with a sensor glucose value <70 mg/dL or > 180 mg/dL, respectively. Daytime (8 am to 9 pm) and nighttime (9 pm to 8 am) glycemic excursions were calculated separately. Multilevel models estimated the between- and within-person association between the night prior to, or the same day, time spent in hypoglycemia or hyperglycemia and cognitive performance (each cognitive test was modeled separately). To evaluate the effect of between-person differences, person-level variables were calculated as the mean across the study and grand-mean centered. To evaluate the effect of within-person fluctuations, day-level variables were calculated as deviations from these person-level means.

Within-person fluctuations in nighttime hypoglycemia were associated with daytime processing speed. Specifically, participants who spent a higher percentage of time in hypoglycemia than their average percentage the night prior to assessment performed slower than their average performance on the processing speed test (Digit Symbol Matching median reaction time, b = 94.16, p = 0.042), while same day variation in hypoglycemia was not associated with variation in Digit Symbol Matching performance. This association remained significant (b = 97.46, p = 0.037) after controlling for within-person and between-person effects of negative affect. There were no significant within-person associations between time spent in hyperglycemia and Digit Symbol Matching, nor day/night hypoglycemia or hyperglycemia and Gradual Onset CPT or Multiple Object Tracking.

Our findings from this EMA study suggest that when individuals with T1D experience more time in hypoglycemia at night (compared to their average), they have slower processing speed the following day, while same day hypoglycemia and hyperglycemia does not similarly impact processing speed performance. These results showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive variation in real world settings that have direct clinical applications for optimizing cognitive performance. Future research with larger samples is needed to replicate these findings.