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Title: Gray matter abnormalities in type 1 and type 2 diabetes : a dual disorder ALE quantification
Authors: Yu, KKK 
Cheing, GLY 
Cheung, C
Kranz, GS 
Cheung, AKK 
Issue Date: Jun-2021
Source: Frontiers in neuroscience, June 2021, v. 15, 638861
Abstract: Aims/hypothesis: Diabetes mellitus (DM) is associated with comorbid brain disorders. Neuroimaging studies in DM revealed neuronal degeneration in several cortical and subcortical brain regions. Previous studies indicate more pronounced brain alterations in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM). However, a comparison of both types of DM in a single analysis has not been done so far. The aim of this meta-analysis was to conduct an unbiased objective investigation of neuroanatomical differences in DM by combining voxel-based morphometry (VBM) studies of T1DM and T2DM using dual disorder anatomical likelihood estimation (ALE) quantification.
Methods: PubMed, Web of Science and Medline were systematically searched for publications until June 15, 2020. VBM studies comparing gray matter volume (GMV) differences between DM patients and controls at the whole-brain level were included. Study coordinates were entered into the ALE meta-analysis to investigate the extent to which T1DM, T2DM, or both conditions contribute to gray matter volume differences compared to controls.
Results: Twenty studies (comprising of 1,175 patients matched with 1,013 controls) were included, with seven studies on GMV alterations in T1DM and 13 studies on GMV alterations in T2DM. ALE analysis revealed seven clusters of significantly lower GMV in T1DM and T2DM patients relative to controls across studies. Both DM subtypes showed GMV reductions in the left caudate, right superior temporal lobe, and left cuneus. Conversely, GMV reductions associated exclusively with T2DM (>99% contribution) were found in the left cingulate, right posterior lobe, right caudate and left occipital lobe. Meta-regression revealed no significant influence of study size, disease duration, and HbA1c values.
Conclusions/interpretation: Our findings suggest a more pronounced gray matter atrophy in T2DM compared to T1DM. The increased risk of microvascular or macrovascular complications, as well as the disease-specific pathology of T2DM may contribute to observed GMV reductions.
Keywords: Anatomical likelihood estimation
Diabetes mellitus
Systematic review
Voxel-based morphometry
Publisher: Frontiers Research Foundation
Journal: Frontiers in neuroscience 
ISSN: 1662-453X
DOI: 10.3389/fnins.2021.638861
Rights: © 2021 Yu, Cheing, Cheung, Kranz and Cheung. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) ( The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Yu KKK, Cheing GLY, Cheung C, Kranz GS and Cheung AK-K (2021) Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification. Front. Neurosci. 15:638861 is available at
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