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OBJECTIVE Diabetic peripheral neuropathy (DPN) has hitherto been considered a disease of the peripheral nervous system only, with central nervous system (CNS) involvement largely overlooked. The aim of this study was to investigate any differences in brain structure in subjects with DPN. RESEARCH DESIGN AND METHODS Thirty-six subjects with type 1 diabetes (No DPN [n = 18], Painful DPN [n = 9], Painless DPN [n = 9]) underwent neurophysiological assessment to quantify the severity of DPN. All subjects, including 18 healthy volunteers (HVs), underwent volumetric brain magnetic resonance imaging at 3 Tesla. RESULTS Adjusted peripheral gray matter volume was statistically significantly lower in subjects with painless and painful DPN (mean 599.6 mL [SEM 9.8 mL] and 585.4 mL [10.0 mL], respectively) compared with those with No DPN (626.5 mL [5.7 mL]) and HVs (639.9 mL [7.2 mL]; ANCOVA, P = 0.001). The difference in adjusted peripheral gray matter volume between subjects with No DPN and HVs and those with Painful DPN and Painless DPN was not statistically significant (P = 0.16 and 0.30, respectively). Voxel-based morphometry analyses revealed greater localized volume loss in the primary somatosensory cortex, supramarginal gyrus, and cingulate cortex (corrected P < 0.05) in DPN subjects. CONCLUSIONS This is the first study to focus on structural changes in the brain associated with DPN. Our findings suggest increased peripheral gray matter volume loss, localized to regions involved with somatosensory perception in subjects with DPN. This may have important implications for the long-term prognosis of DPN.