Simulation-Based Evaluation of Treatment Adjustment to Exercise in Type 1 Diabetes

Regular exercise is beneficial and recommended for people with type 1 diabetes, but increased glucose demand and changes in insulin sensitivity require treatment adjustments to prevent exercise-induced hypoglycemia. Several different adjustment strategies based on insulin bolus reductions and additional carbohydrate intake have been proposed, but large inter- and intraindividual variability and studies using different exercise duration, intensity, and timing impede a direct comparison of their effects. In this study, we use a mathematical model of the glucoregulatory system and implement published guidelines and strategies in-silico to provide a direct comparison on a single 'typical' person on a standard day with three meals. We augment this day by a broad range of exercise scenarios combining different intensity and duration of the exercise session, and different timing with respect to adjacent meals. We compare the resulting blood glucose trajectories and use summary measures to evaluate the time-in-range and risk scores for hypo- and hyperglycemic events for each simulation scenario, and to determine factors that impede prevention of hypoglycemia events. Our simulations suggest that the considered strategies and guidelines successfully minimize the risk for acute hypoglycemia. At the same time, all adjustments substantially increase the risk of late-onset hypoglycemia compared to no adjustment in many cases. We also find that timing between exercise and meals and additional carbohydrate intake during exercise can lead to non-intuitive behavior due to superposition of meal- and exercise-related glucose dynamics. Increased insulin sensitivity appears as a major driver of non-acute hypoglycemic events. Overall, our results indicate that further treatment adjustment might be required both immediately following exercise and up to several hours later, but that the intricate interplay between different dynamics makes it difficult to provide generic recommendations. However, our simulation scenarios extend substantially beyond the original scope of each model component and proper model validation is warranted before applying our in-silico results in a clinical setting.