Alterations in White Matter Structure in Young Children With Type 1 Diabetes

  1. for the Diabetes Research in Children Network (DirecNet)*
  1. 1Department of Psychiatry and Behavioral Sciences, Center for Interdisciplinary Brain Sciences Research, Stanford, CA
  2. 2Departments of Psychiatry, Neurology, and Radiology, Washington University in St. Louis, St. Louis, MO
  3. 3Pediatric Endocrinology, Yale University, New Haven, CT
  4. 4Department of Pediatrics, Stanford University, Stanford, CA
  5. 5Pediatric Endocrinology, Nemours Children’s Clinic, Jacksonville, FL
  6. 6Departments of Pediatrics and Medicine, Washington University in St. Louis, St. Louis, MO
  7. 7Pediatric Endocrinology, University of Iowa, Iowa City, IA
  8. 8Jaeb Center for Health Research, Tampa, FL
  9. 9Department of Radiology, Stanford University, Stanford, CA
  1. Corresponding author: Naama Barnea-Goraly, direcnet{at}


OBJECTIVE To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children.

RESEARCH DESIGN AND METHODS Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition.

RESULTS Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects.

CONCLUSIONS These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.

  • Received June 11, 2013.
  • Accepted October 8, 2013.

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