title: Prospectively determined impact of type 1 diabetes on brain volume during development.
abstract: OBJECTIVE
  The impact of type 1 diabetes mellitus (T1DM) on the developing central nervous system is not well understood. Cross-sectional, retrospective studies suggest that exposure to glycemic extremes during development is harmful to brain structure in youth with T1DM. However, these studies cannot identify brain regions that change differentially over time depending on the degree of exposure to glycemic extremes.
  
  
  METHODS
  We performed a longitudinal, prospective structural neuroimaging study of youth with T1DM (n = 75; mean age = 12.5 years) and their nondiabetic siblings (n = 25; mean age = 12.5 years). Each participant was scanned twice, separated by 2 years. Blood glucose control measurements (HbA(1c), glucose meter results, and reports of severe hypoglycemia) were acquired during the 2-year follow-up. Sophisticated image registration algorithms were performed, followed by whole brain and voxel-wise statistical analyses of the change in gray and white matter volume, controlling for age, sex, and age of diabetes onset.
  
  
  RESULTS
  The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up. However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05). Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05).
  
  
  CONCLUSIONS
  These results demonstrate that within diabetes, exposure to hyperglycemia and severe hypoglycemia may result in subtle deviation from normal developmental trajectories of the brain.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Perantie
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Koller
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Weaver
authors.forename: Heather M
authors.initials: HM
authors.lastname: Lugar
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Black
authors.forename: Neil H
authors.initials: NH
authors.lastname: White
authors.forename: Tamara
authors.initials: T
authors.lastname: Hershey
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D001927:Brain Diseases / Q000209:etiology; D002648:Child; D002657:Child Development; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000503:physiopathology; D007003:Hypoglycemia / Q000209:etiology / Q000503:physiopathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D009929:Organ Size; D009928:Organ Specificity; D011446:Prospective Studies; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human