{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T17:01:35Z","timestamp":1771952495585,"version":"3.50.1"},"reference-count":31,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Science and Technology Major Project","award":["2023SHZDZX02"],"award-info":[{"award-number":["2023SHZDZX02"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2022ZD0213400"],"award-info":[{"award-number":["2022ZD0213400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271627"],"award-info":[{"award-number":["82271627"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Diabetes (DM) affects brain volume and white matter hyperintensity (WMH), but whether regional gray matter volume (GMV) and tract-specific WMH progress in the prediabetes (PreDM) stage remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We investigate brain structural changes across 3 distinct glycemic states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 512 participants (122 with DM, 109 with PreDM, and 281 controls) using advanced neuroimaging techniques. High-resolution structural T1-weighted magnetic resonance images and FLAIR (fluid-attenuated inversion recovery) images were acquired, complemented by cognitive assessments, grip strength measurements, and gait speed testing. We performed correlational analyses to examine the relationships between observed brain changes, cognitive performance, and motor function across different levels of glycemic states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found substantial changes in GMV in DM, especially in areas responsible for movement and coordination, including the bilateral cerebellum, right precentral gyrus, and left postcentral gyrus (P &amp;lt; .001 uncorrected with cluster size &amp;gt; 500). These brain changes were associated with decreases in cognitive test scores (Montreal Cognitive Assessment; P = .04), gait speed (P &amp;lt; .05), and right-hand grip strength (P &amp;lt; .05)\u2014effects not seen in the prediabetic group. We observed significantly higher WMH index across 20 tracts in DM brains (P &amp;lt; .05; false discovery rate [FDR]-corrected). Glycemic levels positively correlated with WMH index in multiple tracts (P &amp;lt; .05; FDR-corrected).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study illuminates DM as a powerful force in cerebral architecture, challenging the notion of a gradual decline beginning in PreDM. These insights not only underscore the critical importance of DM prevention but also hint at the brain's remarkable resilience in the face of early metabolic challenges.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf248","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:45:58Z","timestamp":1745912758000},"page":"3354-3363","source":"Crossref","is-referenced-by-count":1,"title":["Regional Brain Structure Alterations in Diabetes but Not Prediabetes"],"prefix":"10.1210","volume":"110","author":[{"given":"Liangqi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiology, Shanghai Geriatric Medical Center , Shanghai 201104 ,","place":["China"]},{"name":"Department of Radiology, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Human Phenome Institute, Fudan University , Shanghai 201203 ,","place":["China"]},{"name":"School of Life Sciences, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huandong","family":"Lin","sequence":"additional","affiliation":[{"name":"Human Phenome Institute, Fudan University , Shanghai 201203 ,","place":["China"]},{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Institute for Metabolic Diseases, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai 200062 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Institute for Metabolic Diseases, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-9610","authenticated-orcid":false,"given":"Chu-Chung","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Psychology and Cognitive Science, East China Normal University, Institute of Cognitive Neuroscience , Shanghai 200062 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3288-6259","authenticated-orcid":false,"given":"Chun-Yi Zac","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Chung Yuan Christian University , Taoyuan 32023 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-7796","authenticated-orcid":false,"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Human Phenome Institute, Fudan University , Shanghai 201203 ,","place":["China"]},{"name":"Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University , Shanghai 200032 ,","place":["China"]},{"name":"Institute for Metabolic Diseases, Fudan University , Shanghai 200032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"issue":"10","key":"2025111718534101100_dgaf248-B1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41574-018-0048-7","article-title":"Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications","volume":"14","author":"Biessels","year":"2018","journal-title":"Nat Rev Endocrinol"},{"issue":"1","key":"2025111718534101100_dgaf248-B2","first-page":"90","article-title":"Glucose tolerance status and risk of dementia in the community: the Hisayama study","volume":"115","author":"Ohara","year":"2013","journal-title":"Neurology"},{"issue":"11","key":"2025111718534101100_dgaf248-B3","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1007\/s001250050588","article-title":"Association of diabetes mellitus and dementia: the Rotterdam study","volume":"39","author":"Ott","year":"1996","journal-title":"Diabetologia"},{"issue":"11","key":"2025111718534101100_dgaf248-B4","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.2337\/db10-0539","article-title":"Accelerated progression from mild cognitive impairment to dementia in people with diabetes","volume":"59","author":"Xu","year":"2010","journal-title":"Diabetes"},{"issue":"4","key":"2025111718534101100_dgaf248-B5","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S2213-8587(19)30405-X","article-title":"Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression","volume":"8","author":"van Sloten","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"11","key":"2025111718534101100_dgaf248-B6","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1212\/WNL.0b013e3181f25f06","article-title":"Progression of brain atrophy and cognitive decline in diabetes mellitus: a 3-year follow-up","volume":"75","author":"van Elderen","year":"2010","journal-title":"Neurology"},{"issue":"28","key":"2025111718534101100_dgaf248-B7","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1093\/eurheartj\/ehz100","article-title":"Associations between vascular risk factors and brain MRI indices in UK biobank","volume":"40","author":"Cox","year":"2019","journal-title":"Eur Heart J"},{"issue":"12","key":"2025111718534101100_dgaf248-B8","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1097\/JGP.0b013e31818b40fc","article-title":"Association of type 2 diabetes with depression, brain atrophy, and reduced fine motor speed in a 60-to 64-year-old community sample","volume":"16","author":"Kumar","year":"2008","journal-title":"Am J Geriatr Psychiatry"},{"issue":"12","key":"2025111718534101100_dgaf248-B9","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1007\/s00125-003-1235-0","article-title":"Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI","volume":"46","author":"den Heijer","year":"2003","journal-title":"Diabetologia"},{"key":"2025111718534101100_dgaf248-B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pnmrs.2018.11.001","article-title":"MR approaches in neurodegenerative disorders","volume":"108","author":"Blamire","year":"2018","journal-title":"Prog Nucl Magn Reson Spectrosc"},{"issue":"11","key":"2025111718534101100_dgaf248-B11","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.2337\/dc17-1185","article-title":"Diabetes, prediabetes, and brain volumes and subclinical cerebrovascular disease on MRI: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS)","volume":"40","author":"Schneider","year":"2017","journal-title":"Diabetes Care"},{"issue":"25","key":"2025111718534101100_dgaf248-B12","doi-asserted-by":"crossref","first-page":"e3956","DOI":"10.1097\/MD.0000000000003956","article-title":"Gray matter alterations and correlation of nutritional intake with the gray matter volume in prediabetes","volume":"95","author":"Hou","year":"2016","journal-title":"Medicine (Baltimore)"},{"issue":"2","key":"2025111718534101100_dgaf248-B13","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/ana.24712","article-title":"Development of white matter hyperintensity is preceded by reduced cerebrovascular reactivity","volume":"80","author":"Sam","year":"2016","journal-title":"Ann Neurol"},{"issue":"5","key":"2025111718534101100_dgaf248-B14","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/hbm.26196","article-title":"Sex disparity of cerebral white matter hyperintensity in the hypertensive elderly: the Shanghai Changfeng study","volume":"44","author":"Wang","year":"2023","journal-title":"Hum Brain Mapp"},{"issue":"12","key":"2025111718534101100_dgaf248-B15","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.2337\/dc18-1132","article-title":"Prediabetes is associated with structural brain abnormalities: the Maastricht study","volume":"41","author":"van Agtmaal","year":"2018","journal-title":"Diabetes Care"},{"issue":"4","key":"2025111718534101100_dgaf248-B16","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s00125-018-4805-x","article-title":"The PNPLA3 rs738409 C &gt; G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes","volume":"62","author":"Xia","year":"2019","journal-title":"Diabetologia"},{"key":"2025111718534101100_dgaf248-B17","volume-title":"Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications","author":"WHO","year":"1999"},{"issue":"3","key":"2025111718534101100_dgaf248-B18","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","article-title":"Unified segmentation","volume":"26","author":"Ashburner","year":"2005","journal-title":"Neuroimage"},{"issue":"9","key":"2025111718534101100_dgaf248-B19","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1007\/s00429-016-1193-1","article-title":"Reproducibility of hormone-driven regional grey matter volume changes in women using SPM8 and SPM12","volume":"221","author":"De Bondt","year":"2016","journal-title":"Brain Struct Funct"},{"issue":"1","key":"2025111718534101100_dgaf248-B20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/nimg.2001.0786","article-title":"A voxel-based morphometric study of ageing in 465 normal adult human brains","volume":"14","author":"Good","year":"2001","journal-title":"Neuroimage"},{"issue":"2","key":"2025111718534101100_dgaf248-B21","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.neuroimage.2012.04.014","article-title":"Multiple testing corrections, nonparametric methods, and random field theory","volume":"62","author":"Nichols","year":"2012","journal-title":"Neuroimage"},{"key":"2025111718534101100_dgaf248-B22","unstructured":"Wang L, Lin H, Zhao Z, et al \u00a0Regional Brain Structure Alterations in Diabetes but Not Prediabetes supplementary materials. Figshare. 2025. 10.6084\/m9.figshare.28903826.v1"},{"key":"2025111718534101100_dgaf248-B23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.neulet.2015.08.030","article-title":"Cerebral alterations of type 2 diabetes mellitus on MRI: a pilot study","volume":"606","author":"Peng","year":"2015","journal-title":"Neurosci Lett"},{"issue":"12","key":"2025111718534101100_dgaf248-B24","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.2337\/dc13-0143","article-title":"Brain atrophy in type 2 diabetes: regional distribution and influence on cognition","volume":"36","author":"Moran","year":"2013","journal-title":"Diabetes Care"},{"issue":"3","key":"2025111718534101100_dgaf248-B25","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1007\/s00125-018-4778-9","article-title":"Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study","volume":"62","author":"Callisaya","year":"2019","journal-title":"Diabetologia"},{"issue":"8","key":"2025111718534101100_dgaf248-B26","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1016\/j.ejrad.2011.04.025","article-title":"Mapping the brain in type II diabetes: voxel-based morphometry using DARTEL","volume":"81","author":"Chen","year":"2012","journal-title":"Eur J Radiol"},{"issue":"16","key":"2025111718534101100_dgaf248-B27","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.4103\/1673-5374.139482","article-title":"Brain structural changes and their correlation with vascular disease in type 2 diabetes mellitus patients: a voxel-based morphometric study","volume":"9","author":"Wang","year":"2014","journal-title":"Neural Regen Res"},{"issue":"5","key":"2025111718534101100_dgaf248-B28","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0896-6273(02)00698-0","article-title":"Complex movements evoked by microstimulation of precentral cortex","volume":"34","author":"Graziano","year":"2002","journal-title":"Neuron"},{"key":"2025111718534101100_dgaf248-B29","first-page":"1675","article-title":"Comparison of gait performance in three attention demand tasks during extended timed-up and go test in elderly with diabetic peripheral neuropathy","volume":"17","author":"Azizan","year":"2021","journal-title":"Malays J Med Health Sci"},{"key":"2025111718534101100_dgaf248-B30","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.neulet.2017.08.071","article-title":"Grip force control and hand dexterity are impaired in individuals with diabetic peripheral neuropathy","volume":"659","author":"Lima","year":"2017","journal-title":"Neurosci Lett"},{"issue":"9","key":"2025111718534101100_dgaf248-B31","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1016\/j.clinph.2013.04.002","article-title":"Grip force control during simple manipulation tasks in non-neuropathic diabetic individuals","volume":"124","author":"de Freitas","year":"2013","journal-title":"Clin Neurophysiol"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf248\/63031307\/dgaf248.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/12\/3354\/63031307\/dgaf248.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/12\/3354\/63031307\/dgaf248.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T23:54:15Z","timestamp":1763423655000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/12\/3354\/8122499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,4,30]]},"published-print":{"date-parts":[[2025,11,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf248","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,4,30]]}}}