Neural correlates of slower gait in middle-aged persons with childhood-onset type 1 diabetes mellitus: The impact of accelerated brain aging

Aims: We aimed to determine if neuroimaging characteristics of gray and white matter are associated with gait speed in middle-aged individuals with childhood-onset type 1 diabetes (T1D), and whether associations are independent of diabetic peripheral neuropathy (DPN) status. Methods: In a cohort of 100 middle-aged adults with childhood-onset T1D (aged 49.2 +/- 7.0 years, 50F/50M), we assessed cross-sectional associations of DPN, severity of white matter hyperintensities (WMH; Fazekas score), and regional gray matter volume (GMV) with gait speed. Associations were tested separately and combined in linear regression models adjusted for diabetes duration and locomotor risk factors. Results: Average gait speed was 1.3 m/s, with 52% of participants walking below the age-appropriate range of 1.3-1.5 m/s. In separate models, higher WMH severity (beta = -0.27, p = 0.01) and smaller caudate GMV (beta = -0.21, p = 0.04), but not DPN (beta = -0.20, p = 0.08) were associated with slower gait speed. When combined, only WMH severity remained significant (beta = -0.22, p = 0.04). Conclusions: More than half of participants walked more slowly than expected based on age. Gait speed was slower among those with more severe WMH independent of locomotor risk factors. Gait slowing in middle-aged persons with T1D may reflect brain changes, and thus, deserve further attention.