{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T14:13:25Z","timestamp":1774448005638,"version":"3.50.1"},"reference-count":43,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3144,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2,1]]},"abstract":"<jats:p>Decreased white and gray matter volumes have been reported in youth with type 1 diabetes mellitus (T1DM), but the effects of hyperglycemia on white matter integrity have not been quantitatively assessed during brain development. We performed diffusion tensor imaging, using two complimentary approaches\u2014region-of-interest and voxelwise tract-based spatial statistics\u2014to quantify white matter integrity in a large retrospective study of T1DM youth and control participants. Exposure to chronic hyperglycemia, severe hyperglycemic episodes, and severe hypoglycemia, as defined in the Diabetes Control and Complications Trial (DCCT), were estimated through medical records review, HbA1c levels, and interview of parents and youth. We found lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the T1DM group. A history of three or more severe hyperglycemic episodes was associated with reduced anisotropy and increased diffusivity in the superior parietal lobule and increased diffusivity in the hippocampus. These results add microstructural integrity of white matter to the range of structural brain alterations seen in T1DM youth and suggest vulnerability of the superior parietal lobule, hippocampus, and thalamus to glycemic extremes during brain development. Longitudinal analyses will be necessary to determine how these alterations change with age or additional glycemic exposure.<\/jats:p>","DOI":"10.2337\/db12-0696","type":"journal-article","created":{"date-parts":[[2012,11,9]],"date-time":"2012-11-09T05:26:49Z","timestamp":1352438809000},"page":"581-589","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":67,"title":["White Matter Microstructural Integrity in Youth With Type 1 Diabetes"],"prefix":"10.2337","volume":"62","author":[{"given":"Jo Ann V.","family":"Antenor-Dorsey","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerrel","family":"Rutlin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana C.","family":"Perantie","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil H.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Maria","family":"Arbelaez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua S.","family":"Shimony","sequence":"additional","affiliation":[{"name":"Department of Radiology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Hershey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri"},{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, Missouri"},{"name":"Department of Radiology, Washington University School of Medicine, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2013,1,17]]},"reference":[{"key":"2022031210151891900_B1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.2337\/dc08-1657","article-title":"Central nervous system function in youth with type 1 diabetes 12 years after disease onset","volume":"32","author":"Northam","year":"2009","journal-title":"Diabetes Care"},{"key":"2022031210151891900_B2","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.2337\/dc10-2164","article-title":"The feasibility of detecting neuropsychologic and neuroanatomic effects of type 1 diabetes in young children","volume":"34","author":"Aye","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031210151891900_B3","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.2337\/db11-0589","article-title":"Prospectively determined impact of type 1 diabetes on brain volume during development","volume":"60","author":"Perantie","year":"2011","journal-title":"Diabetes"},{"key":"2022031210151891900_B4","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.2337\/dc07-0351","article-title":"Regional brain volume differences associated with hyperglycemia and severe hypoglycemia in youth with type 1 diabetes","volume":"30","author":"Perantie","year":"2007","journal-title":"Diabetes Care"},{"key":"2022031210151891900_B5","first-page":"A57","article-title":"Evidence for reduced gray matter density in patients with type 1 diabetes as measured by magnetic resonance imaging","volume":"52","author":"Musen","year":"2004","journal-title":"Diabetes"},{"key":"2022031210151891900_B6","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1007\/s00125-006-0283-7","article-title":"Voxel-based morphometry demonstrates reduced grey matter density on brain MRI in patients with diabetic retinopathy","volume":"49","author":"Wessels","year":"2006","journal-title":"Diabetologia"},{"key":"2022031210151891900_B7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jpeds.2008.03.005","article-title":"Prevalence of structural central nervous system abnormalities in early-onset type 1 diabetes mellitus","volume":"153","author":"Ho","year":"2008","journal-title":"J Pediatr"},{"key":"2022031210151891900_B8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.2337\/db09-1117","article-title":"Hippocampal volumes in youth with type 1 diabetes","volume":"59","author":"Hershey","year":"2010","journal-title":"Diabetes"},{"key":"2022031210151891900_B9","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1007\/s00234-005-1387-3","article-title":"Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus","volume":"47","author":"Sarac","year":"2005","journal-title":"Neuroradiology"},{"key":"2022031210151891900_B10","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1097\/01.jnen.0000248546.13176.d4","article-title":"Differential neuropathies in hyperglycemic and hypoglycemic diabetic rats","volume":"65","author":"Jamali","year":"2006","journal-title":"J Neuropathol Exp Neurol"},{"key":"2022031210151891900_B11","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s004010100459","article-title":"Hypoglycemic neuropathy","volume":"102","author":"Mohseni","year":"2001","journal-title":"Acta Neuropathol"},{"key":"2022031210151891900_B12","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1008069","article-title":"Detection of blast-related traumatic brain injury in U.S. military personnel","volume":"364","author":"Mac Donald","year":"2011","journal-title":"N Engl J Med"},{"key":"2022031210151891900_B13","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.biopsych.2009.02.032","article-title":"Diffuse microstructural abnormalities of normal-appearing white matter in late life depression: a diffusion tensor imaging study","volume":"66","author":"Shimony","year":"2009","journal-title":"Biol Psychiatry"},{"key":"2022031210151891900_B14","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1523\/JNEUROSCI.4605-08.2009","article-title":"Axial diffusivity is the primary correlate of axonal injury in the experimental autoimmune encephalomyelitis spinal cord: a quantitative pixelwise analysis","volume":"29","author":"Budde","year":"2009","journal-title":"J Neurosci"},{"key":"2022031210151891900_B15","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.2337\/diacare.28.10.2372","article-title":"Frequency and timing of severe hypoglycemia affects spatial memory in children with type 1 diabetes","volume":"28","author":"Hershey","year":"2005","journal-title":"Diabetes Care"},{"key":"2022031210151891900_B16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1399-5448.2007.00274.x","article-title":"Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus","volume":"9","author":"Perantie","year":"2008","journal-title":"Pediatr Diabetes"},{"key":"2022031210151891900_B17","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJM199309303291401","article-title":"The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus","volume":"329","author":"The Diabetes Control and Complications Trial Research Group","year":"1993","journal-title":"N Engl J Med"},{"key":"2022031210151891900_B18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/0002-9343(91)90605-W","article-title":"Epidemiology of severe hypoglycemia in the diabetes control and complications trial","volume":"90","author":"The DCCT Research Group","year":"1991","journal-title":"Am J Med"},{"key":"2022031210151891900_B19","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuroimage.2008.07.009","article-title":"Human brain white matter atlas: identification and assignment of common anatomical structures in superficial white matter","volume":"43","author":"Oishi","year":"2008","journal-title":"Neuroimage"},{"key":"2022031210151891900_B20","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1148\/radiology.212.3.r99au51770","article-title":"Quantitative diffusion-tensor anisotropy brain MR imaging: normative human data and anatomic analysis","volume":"212","author":"Shimony","year":"1999","journal-title":"Radiology"},{"key":"2022031210151891900_B21","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/j.neuroimage.2006.02.024","article-title":"Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data","volume":"31","author":"Smith","year":"2006","journal-title":"Neuroimage"},{"key":"2022031210151891900_B22","first-page":"1","volume-title":"Hum Brain Mapp","year":"2002"},{"key":"2022031210151891900_B23","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: a unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"2022031210151891900_B24","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00401-010-0697-7","article-title":"Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy","volume":"120","author":"Vincent","year":"2010","journal-title":"Acta Neuropathol"},{"key":"2022031210151891900_B25","doi-asserted-by":"crossref","first-page":"e13463","DOI":"10.1371\/journal.pone.0013463","article-title":"Hyperglycemia induces oxidative stress and impairs axonal transport rates in mice","volume":"5","author":"Sharma","year":"2010","journal-title":"PLoS ONE"},{"key":"2022031210151891900_B26","doi-asserted-by":"crossref","first-page":"17757","DOI":"10.1073\/pnas.1010459107","article-title":"Regional aerobic glycolysis in the human brain","volume":"107","author":"Vaishnavi","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022031210151891900_B27","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/j.1749-6632.2002.tb02108.x","article-title":"Oxidative stress and programmed cell death in diabetic neuropathy","volume":"959","author":"Vincent","year":"2002","journal-title":"Ann N Y Acad Sci"},{"key":"2022031210151891900_B28","doi-asserted-by":"crossref","first-page":"623","DOI":"10.2217\/iim.10.60","article-title":"Diffusion tensor imaging of white matter pathology in the mouse brain","volume":"2","author":"Zhang","year":"2010","journal-title":"Imaging Med"},{"key":"2022031210151891900_B29","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1212\/01.WNL.0000113760.72706.D2","article-title":"Diffusion tensor imaging of thalamus correlates with cognition in CADASIL without dementia","volume":"62","author":"O\u2019Sullivan","year":"2004","journal-title":"Neurology"},{"key":"2022031210151891900_B30","first-page":"63","article-title":"Neuropathologic findings in three cases of profound hypoglycemia","volume":"8","author":"Auer","year":"1989","journal-title":"Clin Neuropathol"},{"key":"2022031210151891900_B31","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1399-5448.2008.00431.x","article-title":"Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory","volume":"9","author":"Malone","year":"2008","journal-title":"Pediatr Diabetes"},{"key":"2022031210151891900_B32","doi-asserted-by":"crossref","first-page":"922","DOI":"10.2337\/diacare.14.10.922","article-title":"Severe amnesia after hypoglycemia. Clinical, psychometric, and magnetic resonance imaging correlations","volume":"14","author":"Chalmers","year":"1991","journal-title":"Diabetes Care"},{"key":"2022031210151891900_B33","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/j.1600-0404.1980.tb03047.x","article-title":"Effects of severe hypoglycemia on the human brain. Neuropathological case reports","volume":"62","author":"Kalimo","year":"1980","journal-title":"Acta Neurol Scand"},{"key":"2022031210151891900_B34","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s00125-007-0602-7","article-title":"Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes","volume":"50","author":"Gold","year":"2007","journal-title":"Diabetologia"},{"key":"2022031210151891900_B35","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/mds.1110","article-title":"Hemiballism with hyperglycemia and striatal T1-MRI hyperintensity: an autopsy report","volume":"16","author":"Ohara","year":"2001","journal-title":"Mov Disord"},{"key":"2022031210151891900_B36","doi-asserted-by":"crossref","first-page":"326","DOI":"10.2337\/diabetes.55.02.06.db05-0520","article-title":"Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry","volume":"55","author":"Musen","year":"2006","journal-title":"Diabetes"},{"key":"2022031210151891900_B37","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S1474-4422(03)00554-4","article-title":"Hemiballism: revisiting a classic disorder","volume":"2","author":"Postuma","year":"2003","journal-title":"Lancet Neurol"},{"key":"2022031210151891900_B38","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jpeds.2008.04.048","article-title":"Correlation of clinical and biochemical findings with diabetic ketoacidosis-related cerebral edema in children using magnetic resonance diffusion-weighted imaging","volume":"153","author":"Glaser","year":"2008","journal-title":"J Pediatr"},{"key":"2022031210151891900_B39","doi-asserted-by":"crossref","first-page":"e344","DOI":"10.1097\/PCC.0b013e3182196c9c","article-title":"Change in mean transit time, apparent diffusion coefficient, and cerebral blood volume during pediatric diabetic ketoacidosis treatment","volume":"12","author":"Vavilala","year":"2011","journal-title":"Pediatr Crit Care Med"},{"key":"2022031210151891900_B40","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1007\/s00125-012-2488-2","article-title":"Diffusion tensor imaging in type 1 diabetes: decreased white matter integrity relates to cognitive functions","volume":"55","author":"van Duinkerken","year":"2012","journal-title":"Diabetologia"},{"key":"2022031210151891900_B41","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.2337\/db08-0724","article-title":"Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function","volume":"57","author":"Kodl","year":"2008","journal-title":"Diabetes"},{"key":"2022031210151891900_B42","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0160-2896(92)90014-I","article-title":"Recurrent severe hypoglycemia, intelligence, and speed of information processing","volume":"16","author":"Deary","year":"1992","journal-title":"Intelligence"},{"key":"2022031210151891900_B43","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2337\/diacare.17.7.697","article-title":"Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia","volume":"17","author":"Gold","year":"1994","journal-title":"Diabetes Care"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/62\/2\/581\/569613\/581.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/62\/2\/581\/569613\/581.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:32:23Z","timestamp":1667406743000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/62\/2\/581\/15555\/White-Matter-Microstructural-Integrity-in-Youth"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,17]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,1,17]]},"published-print":{"date-parts":[[2013,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db12-0696","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,17]]}}}