Hippocampal Volumes in Youth with Type 1 Diabetes

  1. Tamara Hershey, Ph.D. (tammy{at},2,3,
  2. Dana C. Perantie, B.S.1,
  3. Jenny Wu, B.A.1,
  4. Patrick M. Weaver, B.A.1,
  5. Kevin J. Black, M.D.1,2,3,4 and
  6. Neil H. White, M.D., C.D.E.5,6
  1. 1Departments of Psychiatry
  2. 2Neurology
  3. 3Radiology
  4. 4Anatomy and Neurobiology and
  5. 5Pediatrics
  6. 6Washington University School of Medicine and St. Louis Children's Hospital


    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.

    Research Design and Methods: We analyzed T1-weighted magnetic resonance images in 95 youth with type 1 diabetes and 49 sibling controls ages 7-17. Youth with diabetes were categorized as having either 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 HbA1c, 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=.016; 3+ larger than all other groups, p<.05). Hyperglycemia exposure was not associated with hippocampal volumes (R2 change =.003, F(1,89)=.31, p=.58, semi-partial r=.06; one outlier removed for high median HbA1c), 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=.002; 3+ larger than all other groups, p<.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.


      • Received July 29, 2009.
      • Accepted September 22, 2009.

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