White Matter Microstructural Alterations in Type 2 Diabetes: A Combined UK Biobank Study of Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging

TY - JOUR

T1 - White Matter Microstructural Alterations in Type 2 Diabetes

T2 - A Combined UK Biobank Study of Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging

AU - Alotaibi, Abdulmajeed

AU - Alqarras, Mostafa

AU - Podlasek, Anna

AU - Almanaa, Abdullah

AU - AlTokhis, Amjad

AU - Aldhebaib, Ali

AU - Aldebasi, Bader

AU - Almutairi, Malak

AU - Tench, Chris R.

AU - Almanaa, Mansour

AU - Mohammadi-Nejad, Ali Reza

AU - Constantinescu, Cris S.

AU - Dineen, Rob A.

AU - Lee, Sieun

N1 - Publisher Copyright: © 2025 by the authors.

PY - 2025/3/5

Y1 - 2025/3/5

N2 - Background and objectives: Type 2 diabetes mellitus (T2DM) affects brain white matter microstructure. While diffusion tensor imaging (DTI) has been used to study white matter abnormalities in T2DM, it lacks specificity for complex white matter tracts. Neurite orientation dispersion and density imaging (NODDI) offers a more specific approach to characterising white matter microstructures. This study aims to explore white matter alterations in T2DM using both DTI and NODDI and assess their association with disease duration and glycaemic control, as indicated by HbA1c levels. Methods and Materials: We analysed white matter microstructure in 48 tracts using data from the UK Biobank, involving 1023 T2DM participants (39% women, mean age 66) and 30,744 non-T2DM controls (53% women, mean age 64). Participants underwent 3.0T multiparametric brain imaging, including T1-weighted and diffusion imaging for DTI and NODDI. We performed region-of-interest analyses on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and isotropic water fraction (IsoVF) to assess white matter abnormalities. Results: We observed reduced FA and ICVF, and increased MD, AD, RD, ODI, and IsoVF in T2DM participants compared to controls (p < 0.05). These changes were associated with longer disease duration and higher HbA1c levels (0 < r ≤ 0.2, p < 0.05). NODDI identified microstructural changes in white matter that were proxies for reduced neurite density and disrupted fibre orientation, correlating with disease progression and poor glucose control. In conclusion, NODDI contributed to DTI in capturing white matter differences in participants with type 2 diabetes, suggesting the feasibility of NODDI in detecting white matter alterations in type 2 diabetes. Type 2 diabetes can cause white matter microstructural abnormalities that have associations with glucose control. Conclusions: The NODDI diffusion model allows the characterisation of white matter neuroaxonal pathology in type 2 diabetes, giving biophysical information for understanding the impact of type 2 diabetes on brain microstructure. Future research should focus on the longitudinal tracking of these microstructural changes to better understand their potential as early biomarkers for cognitive decline in T2DM.

AB - Background and objectives: Type 2 diabetes mellitus (T2DM) affects brain white matter microstructure. While diffusion tensor imaging (DTI) has been used to study white matter abnormalities in T2DM, it lacks specificity for complex white matter tracts. Neurite orientation dispersion and density imaging (NODDI) offers a more specific approach to characterising white matter microstructures. This study aims to explore white matter alterations in T2DM using both DTI and NODDI and assess their association with disease duration and glycaemic control, as indicated by HbA1c levels. Methods and Materials: We analysed white matter microstructure in 48 tracts using data from the UK Biobank, involving 1023 T2DM participants (39% women, mean age 66) and 30,744 non-T2DM controls (53% women, mean age 64). Participants underwent 3.0T multiparametric brain imaging, including T1-weighted and diffusion imaging for DTI and NODDI. We performed region-of-interest analyses on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), orientation dispersion index (ODI), intracellular volume fraction (ICVF), and isotropic water fraction (IsoVF) to assess white matter abnormalities. Results: We observed reduced FA and ICVF, and increased MD, AD, RD, ODI, and IsoVF in T2DM participants compared to controls (p < 0.05). These changes were associated with longer disease duration and higher HbA1c levels (0 < r ≤ 0.2, p < 0.05). NODDI identified microstructural changes in white matter that were proxies for reduced neurite density and disrupted fibre orientation, correlating with disease progression and poor glucose control. In conclusion, NODDI contributed to DTI in capturing white matter differences in participants with type 2 diabetes, suggesting the feasibility of NODDI in detecting white matter alterations in type 2 diabetes. Type 2 diabetes can cause white matter microstructural abnormalities that have associations with glucose control. Conclusions: The NODDI diffusion model allows the characterisation of white matter neuroaxonal pathology in type 2 diabetes, giving biophysical information for understanding the impact of type 2 diabetes on brain microstructure. Future research should focus on the longitudinal tracking of these microstructural changes to better understand their potential as early biomarkers for cognitive decline in T2DM.

KW - diffusion imaging

KW - isotropic volume fraction

KW - microstructural imaging

KW - neurite density

KW - orientation dispersion

KW - type 2 diabetes

KW - white matter

UR - https://www.scopus.com/pages/publications/105001342608

U2 - 10.3390/medicina61030455

DO - 10.3390/medicina61030455

M3 - Article

C2 - 40142266

AN - SCOPUS:105001342608

SN - 1010-660X

VL - 61

JO - Medicina (Lithuania)

JF - Medicina (Lithuania)

IS - 3

M1 - 455

ER -