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• Clinical Article •
Meta-analysis of gray matter volume and resting-state functional connectivity in type 2 diabetes-related cognitive impairment
SUN Zhiyuan  YANG Changzhi  XU Zhenyang  GAO Ming  MAO Dewei  TIAN Xuewen 

DOI:10.12015/issn.1674-8034.2026.07.002.


[Abstract] Objective To investigate structural and functional brain alterations in type 2 diabetes mellitus-associated cognitive dysfunction (TDACD) and to explore potential neural mechanisms.Materials and Methods This study has been registered on the Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD420251115489. Whole-brain voxel-based morphometry (VBM) and resting-state functional magnetic resonance imaging (rs-fMRI) studies were systematically identified and selected according to PRISMA guidelines. A meta-analysis of gray matter volume (GMV) and resting-state functional connectivity (rs-FC) was conducted using seed-based d mapping with permutation of subject images (SDM-PSI), together with sensitivity, heterogeneity, and publication bias testing. Meta-regression analyses were additionally conducted using demographic and clinical variables [age, sex, body mass index (BMI), education, disease duration, glycated hemoglobin A1c (HbA1c), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)].Results Twelve studies (7 functional and 5 structural) were included. Compared with healthy controls (HC), patients with TDACD demonstrated reduced functional activity in the left supramarginal gyrus [SMG, MNI coordinates: (-54, -54, 28), SDM-Z = -4.678, P < 0.000 5] and right inferior frontal gyrus, orbital part [IFGorb, MNI coordinates: (48, 40, -4), SDM-Z = -3.649, P < 0.001)], accompanied by significant gray matter volume reduction in the right putamen [PUT, MNI coordinates: (34, -4, 4), SDM-Z = -2.933, P < 0.01]. Sensitivity analyses confirmed the robustness of these findings. Higher levels of education were associated with milder functional impairment in the right IFGorb (r = 0.558, P < 0.005), whereas no other variables showed significant moderating effects.Conclusions Patients with TDACD exhibit structural and functional abnormalities in the cortical-subcortical circuits; in particular, damage to core brain regions centered on the PUT-SMG-IFGorb may constitute a potential neuroimaging biomarker. These findings provide important clues for the pathological mechanisms, early identification, and neuromodulation interventions of TDACD.
[Keywords] type 2 diabetes；cognitive impairment；magnetic resonance imaging；functional connectivity；gray matter volume；brain networks；meta-regression

SUN Zhiyuan1, 2   YANG Changzhi1   XU Zhenyang1   GAO Ming1   MAO Dewei2*   TIAN Xuewen1*  

1 Shandong Institute of Physical Education, Jinan 250102, China

2 The Chinese University of Hong Kong (Shenzhen Campus), Shenzhen 518172, China

Corresponding author: MAO D W, E-mail: maodewei@cuhk.edu.cn TIAN X W, E-mail: Xuewentian1978@163.com

Conflicts of interest   None.

Received  2026-03-09
Accepted  2026-06-02
DOI: 10.12015/issn.1674-8034.2026.07.002
DOI:10.12015/issn.1674-8034.2026.07.002.

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