title: Hippocampal volumes in youth with type 1 diabetes.
abstract: OBJECTIVE
  Hippocampal neurons in adult animals and humans are vulnerable to severe hypoglycemia and hyperglycemia. Effects are hypothesized to be exacerbated during development, but existing studies on developing human brains are limited. We examined whether hypoglycemia or hyperglycemia experienced during brain development in humans affects hippocampal volumes.
  
  
  METHODS
  We analyzed T1-weighted magnetic resonance images in 95 youth with type 1 diabetes and 49 sibling control subjects aged 7-17 years. Youth with diabetes were categorized as having 0 (n = 37), 1-2 (n = 41), or 3 or more (3+; n = 17) prior severe hypoglycemic episodes. Hyperglycemia exposure was estimated from median lifetime A1C, weighted for duration of diabetes. Stereologic measurements of hippocampal volumes were performed in atlas-registered space to correct for whole brain volume.
  
  
  RESULTS
  Greater exposure to severe hypoglycemia was associated with larger hippocampal volumes (F [3,138] = 3.6, P = 0.016; 3+ larger than all other groups, P < 0.05). Hyperglycemia exposure was not associated with hippocampal volumes (R(2) change = 0.003, F [1,89] = 0.31, P = 0.58, semipartial r = 0.06; one outlier removed for high median A1C), and the 3+ severe hypoglycemia group still had larger hippocampal volumes after controlling for age of onset and hyperglycemia exposure (main effect of hypoglycemia category, F [2,88] = 6.4, P = 0.002; 3+ larger than all other groups, P < 0.01).
  
  
  CONCLUSIONS
  Enlargement of the hippocampus may reflect a pathological reaction to hypoglycemia during brain development, such as gliosis, reactive neurogenesis, or disruption of normal developmental pruning.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. tammy@wustl.edu
authors.forename: Tamara
authors.initials: T
authors.lastname: Hershey
authors.forename: Dana C
authors.initials: DC
authors.lastname: Perantie
authors.forename: Jenny
authors.initials: J
authors.lastname: Wu
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Weaver
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Black
authors.forename: Neil H
authors.initials: NH
authors.lastname: White
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000033:anatomy & histology / Q000473:pathology*; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology*; D007003:Hypoglycemia / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D018579:Patient Selection; D012016:Reference Values; D035781:Siblings