Aims: Diabetic neuropathy (DN) is a serious complication which was hitherto considered a disease of the peripheral nervous system. In this study we sought to investigate in detail changes in brain morphometry in DN. The aim of this study was to identify regional brain volume changes that were specific to DN (painful and painless DN)

Methods: 102 patients with diabetes (34 No-DN, 34 Painless DN and 34 Painful DN) and 34 healthy volunteers underwent detailed clinical and neurophysiological assessments. All subjects underwent 3-dimensional T1-weighted brain MRI (3.0T, Philips). Brain volume analysis was performed using SIENAX ( and Freesurfer (

Results: Groups were matched for age and gender. Total brain volume was significantly lower painful DN [1401.7 (10.7)ml] and painless DN [1393.5 (69.6)ml]) compared to HV [1457.2(79.2)ml] and No DN [1437.2(60.9)ml]; ANOVA p=<0.01). Total grey matter volume was significantly lower in painful DN [713.9(67.1)ml] and painless DN [717.2(42.4)ml] compared to controls (HV [758.4(46.5)]; p=<0.01; No DN [747.3(41.1)]; p=0.015). There were no significant differences in white matter (ANOVA p=0.18) and CSF (ANOVA p=0.23) volumes. Painful DN subjects had significantly lower cortical thickness in the right postcentral gyrus [1.83(0.14)mm vs. HV 1.91(0.13)mm]; (p=0.02); left precentral gyrus [2.31(0.16)mm vs. HV [2.39(0.12)mm]; (p=0.02) and no DN [2.38(0.14)mm]; (p=0.04); and left insula [2.81(0.15)mm] vs. HV [2.97(0.14)mm] p=<0.01).

Conclusion: This is the largest cohort study of brain volume changes in subjects with DN examined to date. We have demonstrated significant reduction in grey matter volume in painful and painless DN subjects. In painful DN this is localised within the somatomotor cortex and insula. These findings highlight significant CNS involvement in DN that provides clues to the pathogenesis of this condition.


D. Selvarajah: None. F. Heiberg-Gibbons: None. I.D. Wilkinson: None. R. Gandhi: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH & Co. KG.

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