Persistence of abnormalities in white matter in children with type 1 diabetes

Diabetologia. 2018 Jul;61(7):1538-1547. doi: 10.1007/s00125-018-4610-6. Epub 2018 Apr 13.

Abstract

Aims/hypothesis: Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes.

Methods: One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA1c levels were obtained every 3 months.

Results: Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02).

Conclusions/interpretation: These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.

Keywords: Brain development; Paediatric diabetes; White matter.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Case-Control Studies
  • Child
  • Child Development
  • Child, Preschool
  • Cognitive Dysfunction / etiology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diffusion Tensor Imaging
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / etiology*
  • Leukoencephalopathies / physiopathology
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Prognosis
  • Risk Factors
  • Time Factors
  • United States

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human