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

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 HbA 1c 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.

Continuous Glucose Monitoring in 2018

“…Those with cognitive impairment had higher HbA1c and higher mean CGM glucose at night, consistent with prior data linking higher HbA1c to greater cognitive impairment. Importantly, a recent longitudinal study in pediatric population including a final population of 118 children with T1D and 58 healthy matched controls demonstrated lower axial diffusivity (a presumed measure of myelination) in children with T1D compared to healthy participants at baseline (P = 0.022) and at 18 months (P = 0.015) (8). In children with T1D, lower lifetime exposure to hyperglycemia (the average of all HbA1c measurements > 42 mmol/mol [ > 6%] from diagnosis to baseline) was associated with higher fractional anisotropy (a measure of white matter development) at 18 months (P = 0.037), and fractional anisotropy was in turn significantly correlated with performance IQ (r = 0.29; P < 0.002) and full-scale IQ (r = 0.23; P < 0.02).…”

“…with an increasing amount of evidence that it is in fact hyperglycemia that damages the brain in young (8), adult (9), and elderly (10) patients. We can therefore expect that future RCTs will focus on time in range (TIR) rather than on the extremes of glycemic excursions (11,12).…”

“…Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial Feig DS 1,2,3 , Donovan LE 4 , Corcoy R 5 , Murphy KE 2,3,6 , Amiel SA 7 , Hunt KF 7,8 , Asztalos E 9 , Barrett JFR 9 , Sanchez JJ 9 , de Leiva A 5 , Hod M 10 , Jovanovic L 11,12 , Keely E 13 This manuscript is also discussed in the article on Technology and Pregnancy, page S-101.…”

“…Digestive and Kidney Diseases, Bethesda, MD; 8 Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI; 9 Aims Blood glucose levels out of target can be a cause and consequence of delayed gastric emptying in people with diabetes. Whether or not improved glycemic control increases risks of hypoglycemia or improves HbA1c levels and gastrointestinal symptoms in diabetic gastroparesis is unknown.…”

Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults

“…This finding is further supported by recent research suggesting accelerated deterioration of measures of processing speed in type 1 diabetes patients and its association with glycemic control in these patients 7 . Moreover, results from young type 1 diabetes patients show, that lower HbA1c is associated with higher fractional anisotropy (FA), a widely employed neuroimaging marker of white matter microstructural integrity derived from Diffusion Tensor Imaging (DTI) 8,9 . Similarly, a relationship of increased HbA1c and decreased fractional anisotropy, indicating white matter damage, as well as reduced neurocognitive performance has been shown in type 1 diabetes patients 7,10 .…”