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

Alotaibi, Abdulmajeed; Alqarras, Mostafa; Podlasek, Anna; Almanaa, Abdullah; AlTokhis, Amjad; Aldhebaib, Ali; Aldebasi, Bader; Almutairi, Malak; Tench, Chris R.; Almanaa, Mansour; Mohammadi-Nejad, Ali-Reza; Constantinescu, Cris S.; Dineen, Rob A.; Lee, Sieun

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


Authors

Abdulmajeed Alotaibi

Mostafa Alqarras

Anna Podlasek

Abdullah Almanaa

Amjad AlTokhis

Ali Aldhebaib

Bader Aldebasi

Malak Almutairi

Chris R. Tench

Mansour Almanaa

Cris S. Constantinescu



Abstract

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.

Citation

Alotaibi, A., Alqarras, M., Podlasek, A., Almanaa, A., AlTokhis, A., Aldhebaib, A., Aldebasi, B., Almutairi, M., Tench, C. R., Almanaa, M., Mohammadi-Nejad, A.-R., Constantinescu, C. S., Dineen, R. A., & Lee, S. (2025). White Matter Microstructural Alterations in Type 2 Diabetes: A Combined UK Biobank Study of Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging. Medicina, 61(3), Article 455. https://doi.org/10.3390/medicina61030455

Journal Article Type Article
Acceptance Date Feb 19, 2025
Online Publication Date Mar 6, 2025
Publication Date 2025-03
Deposit Date May 20, 2025
Publicly Available Date May 20, 2025
Journal Medicina
Print ISSN 1010-660X
Electronic ISSN 1648-9144
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 61
Issue 3
Article Number 455
DOI https://doi.org/10.3390/medicina61030455
Public URL https://nottingham-repository.worktribe.com/output/46312890
Publisher URL https://www.mdpi.com/1648-9144/61/3/455

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medicina-61-00455 (4.5 Mb)
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2025 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).





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