In this project we aim to transform glycemic control during physical activity (PA) among persons with Type 1 diabetes (PwD) by testing three novel complementary approaches toward adjusting insulin delivery before, during, and after PA. The vision behind these approaches is based on the importance of PA for myriad health considerations among PwD—and the reluctance among some to exercise because of fear of hypoglycemia or the need to plan and manage insulin requirements around PA. The approaches we will test each employ separate ways to adjust insulin delivery related to PA: 1) accounting for real-time changes in insulin sensitivity following PA, 2) the amount of “activity-on-board,” which acknowledges the ongoing influence of prior activity on future insulin needs, and 3) anticipated future activity based on past PA patterns. These studies are particularly valuable given the long track-record of the UVa Center for Diabetes Technology (CDT) in both T1D-related engineering innovations and in the CDT’s ability to test novel developments using well-designed clinical trials. It is important to note that all of the studies in this proposal are assessed in the context of the UVA fully- closed loop (FCL) automated insulin delivery system (AID), called APEX, meaning that these new approaches are meant to be incorporated into an AID system in which PwD will not need to announce carbohydrate intake or PA—allowing for a more spontaneous life. Each of the approaches to improving glycemia in the setting of PA is implemented as an algorithmic module added to the APEX FCL controller— and the safety and efficacy of each of the modules is compared to APEX without the given algorithmic module in a randomized, double-blinded, cross-over fashion, allowing direct comparison of the added benefit of each individual module. In Aim 1 of this proposal, we hypothesize that continuously tracking insulin sensitivity and “activity-on- board” (tested separately) and informing the APEX system of these construct to modulate insulin delivery during and after PA will improve glycemia via reduction of the Low Blood Glucose Index (LBGI) compared to APEX alone. Aim 2 will test the hypothesis that an automated system can detect daily patterns of PA and that these patterns can be anticipated by the APEX controller, for example by reducing insulin prior to a likely PA, and improve glycemia (again with LBGI as primary outcome). The trials in both Aims 1&2 will be in a hotel setting with supervised exercise sessions. Aim 3 then focuses on the deployment of the PA-informed APEX system at home during a randomized, cross-over study with 3-week sessions and usual home PA design to confirm the superiority of the exercise-informed AID. These studies will advance T1D management by rigorously testing novel means of glucose management in the setting of PA—with the overall goal of making exercise safer and more feasible for PwD.