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Painful diabetic neuropathy (DN) is a common and distressing complication. New approaches are required to identify novel targets that will serve as a catalyst for future drug discovery programmes. We have demonstrated that responders to neuropathic pain treatment have greater functional connectivity between the insula cortex and the corticolimbic system compared to non-responders. Activity within these networks is mediated by endogenous opioid receptor systems and may hold clues to possible future treatment targets. Methods: 43 painful-DN subjects [responders (VAS Disclosure K.Teh: None. G.P.Sloan: None. I.D.Wilkinson: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc. D.Selvarajah: None. Funding National Institute of Health Research EME grant; European Foundation for the Study of Diabetes

Objective: We have previously demonstrated increased thalamic blood volume and preserved HMRS neuronal metabolite ratios in painful diabetic peripheral neuropathy (P-DPN) . We hypothesised that perfusion measures and neuronal function measured by metabolite ratios may be related. However, as brain metabolite ratios may also be affected by mood disorders, common in P-DPN, this may be a significant confounding factor. Methods: 52 type 1 diabetes (T1D) subjects (18 P-DPN, 23 DPN, 13 without neuropathy-DM-NN) and 18 healthy volunteers (HV) were recruited. 1HMRS was performed at 3T (Philips, Netherlands) . Single voxel spectra were obtained from a 2.25cm3 (15x10x15mm) volume of interest within the thalamus, TE=135ms, TR=1600ms, NSA=256 using point resolved (PRESS) technique. Metabolite ratios were calculated for choline, Creatine, and N-Acetyl Aspartate (NAA) . MR-DSC images were obtained at 3T using a T2*-weighted technique (TR/TE=1250/35ms; 72 dynamics) to assess the passage of bolus intravenous gadolinium-chelate through the thalamus. Results: There was significant negative correlation between NAA/Cr (measure of neuronal function) and measures of depression: Hospital Anxiety and Depression Scale R= -0.33 (p=0.01) , Becks Depression Inventory R= -0.25 (p=.048) ; and anxiety: State-Trait Anxiety inventory- State (STAI-S) R= -.37 (p=.002) , STAI- Trait (T) R= -.32 (p=0.01) and Behavioural Inhibition R= -0.25 (p=0.04) . There were no differences in metabolite ratios between groups; and no significant correlations between perfusion measures and metabolite ratios. Conclusion: This is the first study to show thalamic 1HMRS metabolite ratios are correlated with measures of mood disorders in T1D. The high prevalence of mood disorders in P-DPN and DPN have confounded previous 1HMRS studies and may explain conflicting reports in the literature. The link between neuropathy and mood disorders needs further exploration to understand whether both may arise from a common neurobiological pathway. Disclosure M.Greig: None. G.P.Sloan: None. P.Shillo: None. D.Selvarajah: None. I.D.Wilkinson: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc. Funding European Foundation for the Study of Diabetes (EFSD)

Aim: Our study predicted treatment responses in patients with painful DPN (diabetic peripheral neuropathy) by developing a deep learning model using resting state functional magnetic resonance imaging (fMRI) neuroimaging datasets. Methods: Forty-three consecutive patients who received intravenous lidocaine treatment for painful DPN were assessed. All subjects (responders n=29 and non-responders n=14) underwent detailed clinical and neurophysiological assessments to phenotype their pain sensory profile. Subjects also underwent brain resting-state fMRI. After pre-processing we performed a group concatenated independent component analysis (ICA) set to 30 components and automatically chose 7 highly correlated (p Results: The deep learning treatment response classification in a ten-fold cross validation experiment using 7 ICA spatial maps has a mean AUC of 0.85 and an F1-Score of 0.90. However, with the extra information of all 30 ICA maps the mean AUROC increased to 0.97 with an F1-Score of 0.95. Using only pre-processed resting-state fMRI data achieved suboptimal F1-Score of 69% and AUC score of 44%. Conclusion: Through the use of our deep learning model, we have demonstrated high classification performance. Our method improves painful DPN treatment efficiency by stratifying patients to receive the correct treatment from the outset. We believe to our knowledge this is the first study utilising deep learning methods to classify treatment response in painful DPN. Disclosure K.Teh: None. I.D.Wilkinson: None. G.P.Sloan: None. S.Tesfaye: Advisory Panel; Astellas Pharma Inc., Bayer AG, Grünenthal Group, Nevro Corp., Wörwag Pharma GmbH & Co. KG, Speaker's Bureau; Eva Pharma, Pfizer Inc., Viatris Inc. D.Selvarajah: None. Funding National Instituteof Health Research Efficacy and Mechanism Evaluation Programme (NIHR 129921) European Foundation for the Study of Diabetes (Microvascular Complications Project Grant) University of Sheffield, Health Education England, Knowledge Exchange

Painful diabetic peripheral neuropathy (DPN) is difficult to manage, as treatment response is often varied. The primary aim of this study was to examine differences in pain phenotypes between responders and nonresponders to intravenous lidocaine treatment using quantitative sensory testing. The secondary aim was to explore differences in brain structure and functional connectivity with treatment response. Forty-five consecutive patients who received intravenous lidocaine treatment for painful DPN were screened. Twenty-nine patients who met the eligibility criteria (responders, n = 14, and nonresponders, n = 15) and 26 healthy control subjects underwent detailed sensory profiling. Subjects also underwent multimodal brain MRI. A greater proportion of patients with the irritable (IR) nociceptor phenotype were responders to intravenous lidocaine treatment compared with nonresponders. The odds ratio of responding to intravenous lidocaine was 8.67 times greater (95% CI 1.4–53.8) for the IR nociceptor phenotype. Responders to intravenous lidocaine also had significantly greater mean primary somatosensory cortex cortical volume and functional connectivity between the insula cortex and the corticolimbic circuitry. This study provides preliminary evidence for a mechanism-based approach for individualizing therapy in patients with painful DPN.

Aims: Neuroimaging studies have found structural alterations in brain regions involved in the somatomotor system in diabetic peripheral neuropathy (DPN) and painful-DPN (pDPN). However, most of these studies have had small cohorts of subjects, without consideration of pDPN phenotypes. Here we present the largest DPN neuroimaging study, which examines differences in brain morphology in DPN and phenotypes of painful-DPN. Methods: 229 participants were enrolled, 177 with diabetes (46 no-DPN, 56 painless-DPN and 75 pDPN; 25 irritable [IR] and 50 non-irritable [NIR] phenotype), and 52 healthy volunteers underwent detailed clinical, neurophysiological and quantitative sensory testing (DFNS) assessments, and 3-dimensional T1-weighted brain MRI (3.0T, Phillips). Brain volumetry was performed using Freesurfer. Results: At the post-central gyrus, in comparison with HV (1.92mm±0.11) and NoDPN (1.90mm±0.14), there was a significantly reduced cortical thickness in DPN (1.85mm±0.14), in pDPN (1.87mm±0.12) cortical thickness was reduced compared with HV. At the precentral gyrus, both DPN (2.29mm±0.16) and pDPN (2.28mm±0.16) had significantly reduced cortical thickness compared with HV (2.37mm±0.14) and NoDPN (2.36mm±0.13). At the insula, compared with HV (2.93mm±0.15) the cortical thickness was reduced in DPN (2.85mm±0.18) and pDPN (2.84mm±0.17). The cortical thickness at the pre and postcentral gyrus, and insula correlated with measures of nerve conduction. Moreover, the mean anterior cingulate cortical (ACC) thickness was significantly reduced in the IR- (2.40mm±0.23) compared to NIR-pDPN (2.58mm±0.20; p=0.003). Conclusions: Key somatomotor brain regions have a reduced cortical thickness in patients with DPN and pDPN, which correlate with neurophysiological measures suggestive of an ascending axonopathy. Moreover, the cortical thickness at the ACC differentiated IR and NIR, suggesting neuroplasticity in this region may play a role determining clinical phenotypes in pDPN. Disclosure G. P. Sloan: None. D. Selvarajah: None. K. Teh: None. P. Shillo: None. I. D. Wilkinson: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc.

Objective: We have previously reported increased thalamic vascularity in painful diabetic peripheral neuropathy (PDPN) but the microvascular perfusion characteristics of the other pain processing areas of the brain (Pain Matrix - PM) with or without pain at the time of scanning have not been assessed. The aim thus was to measure the cerebral perfusion of the PM areas using MR-Dynamic Susceptibility Contrast (MR-DSC). Methods: 55 T1DM subjects (20 PDPN, 23 painless-DPN, 13 no-DPN) and 19 healthy volunteers (HV) underwent clinical, neurophysiological and MR-DSC of the passage of IV-gadolinium-chelate through the cerebral vascular bed (3-Tesla, Philips, Netherlands) at rest. The PDPN group was further divided into those that had neuropathic pain during scan - P+ and no pain - P-) and the intensity of pain at the time of scanning was recorded. The Mean Transit Time -MTT and the time-to-peak -TTP concentrations of gadolinium in PM areas (Thalamus, Insular Cortex - IC, Anterior Cingulate Cortex - ACC) were measured. Results: Subjects experiencing spontaneous neuropathic pain (P+, n=10, VAS score≥4) during scanning had shorter mean TTP at the Right-Thalamus: P+ vs. painless-DPN p=0.017, P+ vs. HV p=0.033; Right-IC: P+ vs. painless-DPN p=0.048; and POWM: P+ vs. P- p=0.009, P+ vs. painless-DPN p=0.034, P+ vs. HV p=0.011. The MTT at the Right-Thalamus: P+ vs. HV p=0.043 and at the Left-IC: HV vs. No-DPN p=036, were also significant. Conclusion: This is the first study to show there is altered cerebral perfusion in the pain processing areas of of the brain, with shorter TTP during spontaneous pain at the time of scanning. This seems to be related to a bolus dispersal factor as MTT, and CBF do not match the TTP and the control area is also affected. However, whether this altered perfusion is primary or secondary to the experience of pain is yet to be determined. This novel finding may serve as objective marker of spontaneous neuropathic pain, and a target for the development of novel treatments. Disclosure M. Greig: None. G. P. Sloan: None. P. Shillo: None. D. Selvarajah: None. I. D. Wilkinson: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc. Funding European Foundation for the Study of Diabetes

Painful diabetic neuropathy (DN) is a common, distressing complication of diabetes that is discordant with the degree of peripheral nerve pathology. Very little is known about the cerebral processes involved in pain processing in painful DN. Here we investigated resting-state brain connectivity associated with prolonged pain in DN. Methods: 58 subjects and 36 matched controls were compared with regard to both behavioural measures of pain perception and resting-resting state functional Magnetic Resonance Imaging. The resting-state fMRI brain connectivity was investigated using 20 seed regions located in cardinal pain processing brain regions. Resting-state fMRI analysis was performed using the NITRC Functional Connectivity (CONN) Toolbox and SPM8 (welcome Trust Centre for Neuroimaging London, UK) in Matlab 2014a (the MathWorks, Natick, MA, USA). Functional connectivity matrices between the pre-specified seeds were calculated and the HV versus painful DN phenotype interaction examined. Results: Relative to controls, painful DPN patients displayed increased brain connectivity predominately for the supplementary motor areas (p Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in painful DPN patients. Disclosure K. Teh: None. I. D. Wilkinson: None. P. Shillo: None. G. P. Sloan: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc. D. Selvarajah: None. Funding Health Education England/University of Sheffield Knowledge Exchange Fund; National Institute for Health Research; EME

Aims: The management of painful diabetic peripheral neuropathy (pDPN) is inadequate because the disease mechanisms are not fully understood. We assessed cerebral cellular bioenergetics using phosphorus magnetic resonance spectroscopy (31P-MRS) to determine whether high energy phosphate metabolite levels are altered in the pain processing regions of the brain in pDPN. Methods: A total of 66 subjects, 44 with type 2 diabetes (12 no-DPN, 13 painless-DPN and 19 pDPN) and 12 healthy volunteers (HV), underwent detailed clinical and neurophysiological assessments, and 31P-MRS brain imaging at 3-Tesla (Ingenia, Phillips Healthcare) with voxels placed over the right somatosensory cortex and the thalamus (TR 4s, TR 0.26ms, voxel size 21 x 21 x 40mm3). Measures reflecting cellular bioenergetics (mitochondrial function), ATP to phosphocreatine (PCr) and inorganic phosphate (Pi) ratios (ATP:PCr and ATP:Pi) were calculated. Results: There was a significant group effect in the ATP:PCr ratio at the thalamus (p=0.016) and somatosensory cortex (p=0.025). The ATP:PCr at the thalamus was significantly higher in the pDPN group (0.50±0.06) compared to HV (0.44±0.04, p=0.024) and no-DPN (0.42±0.07, p=0.006). Moreover, the ATP:PCr ratio at the somatosensory cortex was significantly higher in pDPN (0.48 ±0.1) compared to HV (0.38 ±0.1, p=0.035). In addition, the ratio correlated with the numeric pain score ratings during the MRI scan at both brain regions. Conclusions: This is the first study to use 31P-MRS to study cerebral energetics in human-DPN and peripheral painful neuropathies. We demonstrated significantly higher ATP:PCr ratios in patients with pDPN in the somatosensory cortex and thalamus, which correlated with pain severity. This is suggestive of increased cellular energy usage in pain processing regions of the brain, perhaps due to continuous nociceptive inputs. Altered cerebral phosphorus metabolite ratios may serve as a biomarker of neuropathic pain in diabetes. Disclosure G.P. Sloan: None. A. Anton: None. D. Selvarajah: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, Wörwag Pharma. Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, Napp Pharmaceuticals, Novo Nordisk Inc., Pfizer Inc. I.D. Wilkinson: None.

Diabetic distal symmetrical peripheral polyneuropathy (DSP) results in decreased somatosensory cortical gray matter volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has examined whether changes in brain volume alter the functional organization of the somatosensory cortex and how this relates to the various painful DSP clinical phenotypes. In this case-controlled, multimodal brain MRI study of 44 carefully phenotyped subjects, we found significant anatomical and functional changes in the somatosensory cortex. Subjects with painful DSP insensate have the lowest somatosensory cortical thickness, with expansion of the area representing pain in the lower limb to include face and lip regions. Furthermore, there was a significant relationship between anatomical and functional changes within the somatosensory cortex and severity of the peripheral neuropathy. These data suggest a dynamic plasticity of the brain in DSP driven by the neuropathic process. It demonstrates, for the first time in our knowledge, a pathophysiological relationship between a clinically painful DSP phenotype and alterations in the somatosensory cortex.

Using advanced MR neuroimaging we have demonstrated altered brain structure and functional connectivity that could serve as a potential Central Pain Signature (CPS) for painful diabetic neuropathy (DN). However, the key challenge is how to apply this potential biomarker for routine diagnostic purposes. The aim of this study was to examine if the CPS can accurately classify painful DN patients based on a patient’s pain severity. Methods: 53 painful DN patients underwent detailed clinical and neurophysiological assessments. The NTSS-6, a validated questionnaire that measures both the frequency and the intensity of neuropathic pain was used to assess pain severity. Patients were divided into high pain (NTSS-6 score >7) and low pain ( Results: There was no age or gender difference (p > 0.05) between the high and low pain groups. The CPS classified painful DN patients based on their pain intensity with 94% accuracy (AUC 0.98). The positive and negative predictive values were 0.80 and 1.00 respectively. The F1 scores for predicting high pain and low pain were 0.89 and 0.96 respectively. Brain regions identified as the best classifier were the left and right postcentral gyri, thalami, and anterior and posterior cingulate cortices. Conclusions: This novel study demonstrates that a simple, 15-minute MR brain scan can accurately classify painful DN patients according to pain intensities with high accuracy. This assessment tool has a great potential as a biomarker of diabetic neuropathic pain and may serve as a target for future trials of analgesic compounds for painful DN. Disclosure D. Selvarajah: None. K. Teh: None. G.P. Sloan: None. P. Shillo: None. I.D. Wilkinson: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, WÖRWAG Pharma. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., NAPP Pharmaceuticals Limited, Neurometrix, Novo Nordisk Inc., Pfizer Inc. Other Relationship; Self; Impeto Medical. Funding European Foundation for the Study of Diabetes

Aim: The risk of developing mild cognitive impairment (MCI) increases with type 2 diabetes (T2DM). Brain morphometric changes associated with MCI have been described. However Cerebral Blood Flow (CBF) changes in relation to MCI has not been fully investigated. This study aims to investigate regional CBF changes in subjects with T2DM and MCI. Method: Seventy-four age and gender matched subjects [28, T2DM (T2DM); 17, T2DM+MCI (T2DM/MCI) and 29, healthy volunteers (HV)] were recruited. All subjects underwent clinical and questionnaire (Addenbrooke’s Cognitive Assessment [ACE-R]) assessment along with Arterial Spin Labelling (ASL) perfusion Magnetic Resonance Imaging (MRI) of the brain. The ASL data was modelled to yield quantitative arterial CBF maps in neuroanatomical regions involved with cognitive function. Results: Demographic data revealed aged-matched participants between all three groups (mean age 69.3-71.5 years, ANOVA, p = 0.164). Mean age of last education was significantly lower in the T2DM/MCI group (mean±SD;15.1 ±0.9 when compared to the other groups (HV 19.3±5.6, T2DM 17.1±2.9) Kruskal-Wallis, p=0.003. T2DM/MCI ACE-R score (mean±SD; 83±4) was significantly lower compared to other groups (HV=96±2, T2DM=94±3; ANOVA p. Pearson’s correlation revealed significant correlations between ACE-R score and regional CBF measurements in the medial temporal lobes, (p Conclusion: This study demonstrates significantly lower CBF in T2DM MCI subjects in neuroanatomical regions responsible for cognitive function. This may be essential to help understand the pathological mechanisms that occur behind the increased risk of developing cognitive impairment in T2DM. Disclosure L. Hunt: None. D. Selvarajah: 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. I.D. Wilkinson: None.

Objective: Painful diabetic peripheral neuropathy (painful-DPN) causes distressing neuropathic pain that is only partially responsive to treatment. A better understanding of CNS correlates of painful-DPN is vital to develop more effective therapeutics. The aim of this study was to measure cerebral perfusion of the pain processing areas of the brain using MR-Dynamic Susceptibility Contrast (MR-DSC) imaging at rest and under experimental pain condition. Methods: 55 T1DM subjects (20 painful-DPN, 23 painless-DPN, 13 no-DPN) and 19 Healthy Volunteers (HV); underwent detailed clinical and neurophysiological assessment (NISLL+7 tests of nerve function; DN4 questionnaire). MR images were obtained at 3T using a MR-DSC, T2*-weighted technique (TR/TE=1250/35ms; 72 dynamics) to assess the passage of a bolus of intravenous gadolinium-chelate through cerebral vascular bed. Subjects were scanned at baseline and during 90s of heat-pain applied to the right lateral thigh (non-neuropathic area). The time-to-peak (TTP) concentration of gadolinium in regions of interest (ROI): right and left thalamus, right and left sensory cortices (RSC and LSC), was measured. Results: At baseline, although the mean TTP (s) in the ROIs was shorter in the painful-DPN group [e.g., RT: M (SD): 9.22 (1.13) vs. HV 9.83 (0.99), no-DPN 9.59 (0.90), painless-DPN 9.94 (0.97)] this was not statistically significant (p=0.058). However the ΔTTP in response to thermal pain was significantly different between the groups LT (p=0.021), RT (p=0.003), LSC (p=0.009), RSC (p=0.008). Whilst HV respond to thermal pain by shortening the TTP in ROI the painful-DPN group do the reverse (p Conclusion: Subjects with painful-DPN have a paradoxical increase in TTP, indicating that chronic neuropathic pain state may result in a failure to mount a hemodynamic response to external pain and descending inhibition. This novel finding may serve as an objective marker of painful-DPN, and in the future may facilitate the development of novel treatments. Disclosure M. Greig: None. I.D. Wilkinson: None. D. Selvarajah: None. P. Shillo: 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.

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 (www.fmrib.ox.ac.uk/fsl) and Freesurfer (http://surfer.nmr.mgh.harvard.edu/). 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= 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. Disclosure 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.

Aim: Mild Cognitive Impairment (MCI) is thought to be a chronic sequelae of type 2 diabetes (T2DM). Cerebral atrophy is known to be associated with cognitive decline, particularly in dementia. Cerebral tissue volumes, in areas associated with cognitive function, were examined in matched patients with T2DM subjects and early cognitive decline. The aim of this study was to compare T2DM patients with and without MCI to identify regional brain volume changes that were specific to MCI. Method: Seventy-six age and gender matched subjects [30, T2DM+normal cognition (T2DM); 17, T2DM+MCI (T2DM/MCI) and 29, healthy volunteers (HV)] were recruited. All subjects underwent clinical and questionnaire (Addenbrooke’s Cognitive Assessment [ACE-R]) assessments and high-resolution, 3D T1-weighted Magnetic Resonance Imaging (MRI, 3T Philips Ingenia). Cerebral volumes were analysed using voxel based morphometry (VBM, FSL, Oxford). Results: Demographic data revealed aged-matched participants between all three groups (mean age 69.3-71.5 years, ANOVA, p = 0.164). Mean age of last education was significantly lower in the T2DM/MCI group (mean±SD;15.1 ±0.9 when compared to the other groups (HV 19.3±5.6, T2DM 17.1±2.9) Kruskal-Wallis, p = 0.003. T2DM/MCI ACE-R score (mean±SD; 83±4) was significantly lower compared to other groups (HV=96±2, T2DM=94±3; ANOVA, p Conclusion: This study demonstrates significantly lower cortical differences in areas associated with cognition in patients with T2DM and early cognitive impairment. Further investigation of both anatomical and functional cerebral involvement is required to examine the pathological mechanisms underlying the increased cognitive impairment risk associated with T2DM. Disclosure L. Hunt: None. D. Selvarajah: 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. I.D. Wilkinson: None.