Background: Glucose variations are common throughout sleep and wakefulness in people with type 1 diabetes mellitus (T1DM). The objective of this investigation was to characterize the time-varying coupling between glucose and unstructured physical activity over a 60-hr period in young adults with T1DM. The hypothesis was that coupling would differ during sleep versus wakefulness and would exhibit circadian variations. Method: Young adults with T1DM treated with an insulin pump participated in the study. Glucose variations were monitored with a continuous glucose monitoring system, and activity was assessed using an activity-monitoring band worn on the nondominant wrist. Simultaneous glucose and physical activity data across a continuous 60-hr period were used for analysis. Wavelet coherence analysis was employed to quantify the coupling between physical activity and glucose. Cosinor analysis was used to assess whether glucose/activity coherence exhibited significant circadian variations. Results: Participants comprised 23 adults, aged 18-30 years, with T1DM. Coherence analysis demonstrated substantial coupling between physical activity and glucose variations during both wakefulness and sleep. For rapid (10-30 min) fluctuations, mean coherence was higher during sleep than wakefulness (F = 10.86, p = .003). Rapid glucose variations consistently led to changes in activity (p = .001) during sleep but not during wake. Cosinor analysis revealed significant circadian modulation of glucose/activity coupling, especially for fluctuation periods 2-4 hr. Conclusions: Unstructured physical activity and glucose variations demonstrated strong time- and frequency-dependent coupling over a 60-hr period in young adults with T1DM, with sleep/wake differences and circadian modulation evident in this relationship.