IIT Project Summary/Abstract The objective of this proposal is to demonstrate a viable, functionally integrated multivariable artificial pancreas that will mitigate meal, physical activity and acute psychological stress challenges without any manual inputs to better regulate glucose levels of people with diabetes. The first generation of artificial pancreas (AP) systems, the hybrid closed-loop AP, collects data from continuous glucose monitoring devices and relies on manual user inputs for mitigating the effects of meals and physical activities. Acute psychological stress and many other physical activities besides planned exercise can affect blood glucose levels and cause challenges to maintaining euglycemia for people with type 1 diabetes. Various physical activities and acute psychological stress events affect the metabolism and sensitivity to insulin in different ways. Hence, their types, intensities and durations, and their individual and concurrent presence must be detected in order to determine the optimal insulin administration. The multivariable artificial pancreas approach provides a well-integrated and user-friendly technology with minimal burden on the user and mitigates the effects of unexpected physical activities and acute psychological stress inducements. Additionally, this technology would be safer by reducing the number and duration of hypoglycemic and hyperglycemic events, compared to APs based exclusively on continuous glucose monitoring device data. Such multivariable AP systems can only be developed by using a sophisticated multivariable approach that uses real-time information from continuous glucose monitoring devices and physiological variables obtained from wearable devices worn in free-living daily life.