Thus, hyperglycaemia adversely affects myelination and nerve fibre structure and integrity in animal models and is associated with lower fractional anisotropy and greater radial diffusivity in cross-sectional human studies. Furthermore, in two studies, greater radial diffusivity and lower fractional anisotropy correlated with greater hyperglycaemia, suggesting hyperglycaemia-induced myelin damage. Using DTI, we and others have observed that children with type 1 diabetes had lower axial diffusivity when compared with age-matched non-diabetic children and that these differences were related to metrics of hyperglycaemia. Streptozotocin-induced diabetic rats display reduced myelination and altered intracellular water shifts in excised sciatic nerves. In animal studies, myelination and fibre integrity are adversely affected by hyperglycaemia. However, in general, a change in diffusivity is not specific to a particular microstructural change and results also may be influenced by other factors, such as packing density, complex fibre architecture and water content. By examining patterns of altered DTI metrics in white matter tracts, myelin and axonal integrity can be inferred in controlled experiments. Mean diffusivity (measures degree of overall water diffusivity) is an average of these effects in white matter and is more commonly used in isotropic media such as grey matter or cerebrospinal fluid. The primary DTI metrics for assessing white matter microstructure are fractional anisotropy (increases with myelination and fibre tract coherence decreases with extracellular diffusion), radial diffusivity (measures water diffusivity perpendicular to the local axonal direction and decreases with myelination) and axial diffusivity (measures water diffusivity parallel to the axonal direction and may decrease with cell swelling, more neurofilaments within axons or axonal branching). DTI measures the movement of water molecules within tissue and is sensitive to the orientation of axons and cell membranes as well as the fraction of intracellular vs extracellular water. This imaging modality allows the detection of white matter structural alterations before gross anatomical changes occur and become apparent on structural (anatomical) MRI. Although previous studies have found altered grey and white matter volume and white matter microstructure in children and adolescents with type 1 diabetes, related to dysglycaemia, no longitudinal studies have examined how diabetes and associated dysglycaemia affects white matter microstructural measures during development.īrain white matter microstructure can be estimated using the MRI-based technique of diffusion tensor imaging (DTI). Grey matter volume continues to increase until approximately 11 years of age but subsequently decreases through adolescence, whereas white matter volume, driven by the ongoing myelination of axons, gradually increases into early adulthood.

Early childhood is a period of rapid myelination and brain development, with total brain volume reaching approximately 90% of adult brain volume by the age of 6 years. The long-term impact of type 1 diabetes on microvascular complications is well documented but effects on the developing brain are less understood. These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population. Fractional anisotropy was positively correlated with performance ( p < 0.002) and full-scale IQ ( p < 0.02).

Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy ( p = 0.037). ResultsĪxial 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. Continuous glucose monitoring profiles and HbA 1c levels were obtained every 3 months. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. 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. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes. 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.

Mazaika serial