{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:04:07Z","timestamp":1788365047560,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000323","name":"Pain Relief Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetes mellitus (DM) is associated with structural grey matter alterations in the brain, including changes in the somatosensory and pain processing regions seen in association with diabetic peripheral neuropathy. In this case\u2010controlled biobank study, we aimed to ascertain differences in grey and white matter anatomy in people with DM compared with non\u2010diabetic controls (NDC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study utilises the UK Biobank prospective, population\u2010based, multicentre study of UK residents. Participants with diabetes and age\/gender\u2010matched controls without diabetes were selected in a three\u2010to\u2010one ratio. We excluded people with underlying neurological\/neurodegenerative disease. Whole brain, cortical, and subcortical volumes (188 regions) were compared between participants with diabetes against NDC corrected for age, sex, and intracranial volume using univariate regression models, with adjustment for multiple comparisons. Diffusion tensor imaging analysis of fractional anisotropy (FA) was performed along the length of 50 white matter tracts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 2404 eligible participants who underwent brain magnetic resonance imaging (NDC,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01803 and DM,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0601). Participants with DM had a mean (\u00b1standard deviation) diagnostic duration of 18\u00a0\u00b1\u00a011\u00a0years, with adequate glycaemic control (HbA1\n                      <jats:sub>C<\/jats:sub>\n                      52\u00a0\u00b1\u00a013\u00a0mmol\/mol), low prevalence of microvascular complications (diabetic retinopathy prevalence, 5.8%), comparable cognitive function to controls but greater self\u2010reported pain. Univariate volumetric analyses revealed significant reductions in grey matter volume (whole brain, total, and subcortical grey matter), with mean percentage differences ranging from 2.2% to 7% in people with DM relative to NDC (all\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0002). The subcortical (bilateral cerebellar cortex, brainstem, thalamus, central corpus callosum, putamen, and pallidum) and cortical regions linked to sensorimotor (bilateral superior frontal, middle frontal, precentral, and postcentral gyri) and visual functions (bilateral middle and superior occipital gyri), all had lower grey matter volumes in people with DM relative to NDC. People with DM had significantly reduced FA along the length of the thalamocortical radiations, thalamostriatal projections, and commissural fibres of the corpus callosum (all;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00\u00b7001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This analysis suggests that anatomic differences in brain regions are present in a cohort with adequately controlled glycaemia without prevalent microvascular disease when compared with volunteers without diabetes. We hypothesise that these differences may predate overt end\u2010organ damage and complications such as diabetic neuropathy and retinopathy. Central nervous system alterations\/neuroplasticity may occur early in the natural history of microvascular complications; therefore, brain imaging should be considered in future mechanistic and interventional studies of DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dmrr.3772","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T06:05:56Z","timestamp":1708063556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Brain alterations in regions associated with end\u2010organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-6918","authenticated-orcid":false,"given":"Jamie","family":"Burgess","sequence":"first","affiliation":[{"name":"Department of Cardiovascular &amp; Metabolic Medicine and the Pain Research Institute Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"de Bezenac","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics Institute of Systems Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon S.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics Institute of Systems Molecular and Integrative Biology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The Walton Centre  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis N.","family":"Petropoulos","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine\u2010Qatar Qatar Foundation Education City  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Garcia\u2010Finana","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"},{"name":"King's Ophthalmology Research Unit Department of Ophthalmology King's College Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varo","family":"Kirthi","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Cuthbertson","sequence":"additional","affiliation":[{"name":"Metabolism and Nutrition Research Group Department of 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University NHS Foundation Trust  Liverpool UK"},{"name":"Centre for Biomechanics and Rehabilitation Technologies Staffordshire University  Staffordshire 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