title: Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children.
abstract: OBJECTIVE
  To investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function.
  
  
  METHODS
  Patients aged 6-18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive assessment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses.
  
  
  RESULTS
  Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at baseline in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes.
  
  
  CONCLUSIONS
  DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia fergus.cameron@rch.org.au.
authors.forename: Fergus J
authors.initials: FJ
authors.lastname: Cameron
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Scratch
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Nadebaum
authors.affiliation: Department of Psychology, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Northam
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Koves
authors.affiliation: Department of Endocrinology and Diabetes, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Juliet
authors.initials: J
authors.lastname: Jennings
authors.affiliation: Washington University, St. Louis, MO.
authors.forename: Kristina
authors.initials: K
authors.lastname: Finney
authors.affiliation: Washington University, St. Louis, MO.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Neil
authors.affiliation: Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wellard
authors.affiliation: Department of Neurology, Royal Children's Hospital, Murdoch Children's Research Institute, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Mackay
authors.affiliation: Washington University, St. Louis, MO.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Inder
mesh_terms: D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D002648:Child; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis*; D016883:Diabetic Ketoacidosis / Q000150:complications* / Q000378:metabolism; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D011446:Prospective Studies
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate