This pilot study tackles the overarching need for driver-state detection through real-world measurements of driver behavior and physiology in at-risk drivers with type 1 diabetes mellitus (DM). 35 drivers (19 DM, 14 comparison) participated. Real-time glucose levels were measured over four weeks with continuous glucose monitor (CGM) wearable sensors. Contemporaneous real-world driving performance and behavior were measured with in-vehicle video and electronic sensor instrumentation packages. Results showed clear links between at-risk glucose levels (particularly hypoglycemia) and changes in driver performance and behavior. DM participants often drove during at-risk glucose levels (low and high) and showed cognitive impairments in key domains for driving, which are likely linked to frequent hypoglycemia. The finding of increased driving risk in DM participants was mirrored in state records of crashes and traffic citations. Combining sensor data and phenotypes of driver behavior can inform patients, caregivers, safety interventions, policy, and design of supportive in-vehicle technology that is responsive to driver state.