OBJECTIVE Diabetic peripheral neuropathy (DPN) alters walking. Yet, the compensatory role of central locomotor circuits remains unclear. We hypothesized that walking outcomes would be more closely related to regional gray matter volumes in older adults with DPN, as compared with nonneuropathic diabetic patients and nondiabetic control subjects.

RESEARCH DESIGN AND METHODS Clinically important outcomes of walking (i.e., speed, stride duration variability, and double support time) were measured in 29 patients with DPN (type 2 diabetes with foot-sole somatosensory impairment), 68 diabetes mellitus (DM) patients (type 2 diabetes with intact foot-sole sensation), and 89 control subjects. Global and regional gray matter volumes were calculated from 3 Tesla magnetic resonance imaging.

RESULTS DPN subjects walked more slowly (P = 0.005) with greater stride duration variability (P < 0.001) and longer double support (P < 0.001) as compared with DM and control subjects. Diabetes was associated with less cerebellar gray matter volume (P < 0.001), but global gray matter volume was similar between groups. DPN subjects with lower gray matter volume globally (P < 0.004) and regionally (i.e., cerebellum, right-hemisphere dorsolateral prefrontal cortex, basal ganglia, P < 0.005) walked more slowly with greater stride duration variability and/or longer double support. Each relationship was stronger in DPN than DM subjects. In control subjects, brain volumes did not relate to walking patterns.

CONCLUSIONS Strong relationships between brain volumes and walking outcomes were observed in the DPN group and to a lesser extent the DM group, but not in control subjects. Individuals with DPN may be more dependent upon supraspinal elements of the motor control system to regulate several walking outcomes linked to poor health in elderly adults.