Evidence map›Paper›PMID 42135912›Full record

ArticleBrain and behavior2026

Causal Links of Type 2 Diabetes and Its Complications With Cortical Modification: A Mendelian Randomization and Mediation Analysis.

Hong Huang, Hanyu Huang, Yanlin Gong, Tengteng Zhou, Yundan Liang, Yichao Wang

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Article in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

Hong HuangDepartment of Pharmacology, Dazhou Vocational and Technical College, Dazhou, Sichuan, People's Republic of China.
Hanyu HuangDepartment of Orthopedic Surgery and Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Yanlin GongDepartment of Pharmacology, Dazhou Vocational and Technical College, Dazhou, Sichuan, People's Republic of China.
Tengteng ZhouDepartment of Pharmacology, Dazhou Vocational and Technical College, Dazhou, Sichuan, People's Republic of China.
Yundan LiangDepartment of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, Sichuan, People's Republic of China.
Yichao WangDivision of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Funding

Chengdu Medical College Research Development Fund CYZZD25-10Development and Regeneration Key Laboratory of Sichuan Province 24 LHFYSZ1-25Sichuan Clinical Research Center for Geriatrics 24 LHLNYX1-04Sichuan Research Center of Applied Psychology, Key Research Base of Philosophy and Social Sciences of Sichuan Province CSXL-24202
6 · The paper itself

Abstract

backgroundType 2 diabetes (T2D) and its complications are linked to cognitive decline over time, accompanied by cortical abnormalities. The causality between T2D and cortical modifications, however, remains elusive.

methodsApplying two-sample Mendelian randomization (MR), we probed causal relationships between T2D and its complications and cortical modifications. Genetic associations were elucidated via linkage disequilibrium score regression and Bayesian colocalization. An instrumental variable-guided protein-protein interaction (PPI) network was constructed and subjected to clustering and pathway analysis. Moreover, a two-step MR strategy was used to identify immune mediators in the causal relationship.

resultsThe results showed that T2D (p = 0.005), T2D with ophthalmic (T2D_OPTH, p = 0.004), or peripheral circulatory (T2D_PERIPH, p = 0.005) complications had a significant impact on reducing isthmus cingulate thickness. T2D_PERIPH led to an increase in the anterior cingulate surface areas, including both the caudal (p = 0.008) and rostral (p = 0.002) regions. Suggested colocalization was exclusive to T2D_OPTH and isthmus thickness, without additional genetic associations. PPI network clustering revealed causal pathway associations beyond conventional diabetes mechanisms, implicating roles in infection, addiction, and neurodegeneration. IL20RA, IgD- CD38dim B cells, HLA DR+ CD4+ T cells, and CD3 on effector memory CD4+ T cells emerged as candidate mediators of the observed causal links.

conclusionOur study uncovers causal associations between T2D and its complications with cortical structure, highlighting the cingulate's particular vulnerability. Immuno-metabolic dysregulation emerges as a mediator in the causal pathway connecting them, underlining inflammation control's critical importance in diabetes management.

Indexed as

Diabetes Mellitus, Type 2Gyrus CinguliHumansMediation AnalysisMendelian Randomization AnalysisPolymorphism, Single NucleotideProtein Interaction Mapscomplicationscortical modificationmediation analysisMendelian randomizationType 2 diabetes

Identifiers

PMID42135912
PMCPMC13176085

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.