Larry A Fox1, Tamara Hershey2, Nelly Mauras3, Ana Maria Arbeláez2, William V Tamborlane4, Bruce Buckingham5, Eva Tsalikian6, Kim Englert3, Mira Raman7, Booil Jo7, Hanyang Shen7, Allan Reiss5,7,8, Paul Mazaika7. 1. Pediatric Endocrinology, Nemours Children's Health System, 807 Children's Way, Jacksonville, FL, 32207, USA. lfox@nemours.org. 2. Department of Psychiatry and Radiology, Washington University in St Louis and the St Louis Children's Hospital, St Louis, MO, USA. 3. Pediatric Endocrinology, Nemours Children's Health System, 807 Children's Way, Jacksonville, FL, 32207, USA. 4. Pediatric Endocrinology, Yale University, New Haven, CT, USA. 5. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. 6. Department of Pediatric Endocrinology, The University of Iowa, Iowa City, IA, USA. 7. Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. 8. Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
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.
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-diabeticchildren, 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-diabeticchildren 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.
Entities:
Keywords:
Brain development; Paediatric diabetes; White matter
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