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Structural and functional alterations of the hippocampal subfields in T2DM with mild cognitive impairment and insulin resistance: A prospective study

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Yang, Chen, Zhang, Huiyan, Ma, Zihan, Fan, Yanjun, Xu, Yanan, Tan, Jian, Tian, Jing, Cao, Jiancang +3 more·2024·Journal of Diabetes
DOI 10.1111/1753-0407.70029PMC PMC11560383
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Abstract

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and is often accompanied by mild cognitive impairment (MCI). The detrimental effects of T2DM and IR on the hippocampus have been extensively demonstrated. Few studies have examined the effects of IR on structure and function of hippocampal subfields in T2DM-MCI patients. METHOD: A total of 104 T2DM patients were recruited in this prospective study and divided into four groups (T2DM-MCI-higherIR, n = 17; T2DM-MCI-lowerIR, n = 32; T2DM-nonMCI-higherIR, n = 19; T2DM-nonMCI-lowerIR, n = 36). Structure and function MRI data were captured. Clinical variables and neuropsychological scores were determined for all participants. Hippocampal subfield volume and functional connectivity were compared among four groups. Partial correlation analysis was performed between imaging indicators, clinical variables, and neuropsychological scores in all patients. RESULTS: T2DM-MCI-higher IR group had the smallest volumes of bilateral hippocampal tail, right subiculum-body, right GC-ML-DG-body, and right CA4-body. IR in right hippocampal tail, right subiculum-body, and right GC-ML-DG-body exerted main effect. Furthermore, elevated functional connectivity was found between right subiculum-body and bilateral dorsolateral prefrontal cortex and right anterior cingulate-medial prefrontal cortex. Hippocampal subfield volume positively correlates with total cholesterol and triglycerides and negatively correlates with fasting insulin. CONCLUSION: The present study found that T2DM-MCI patients have structural and functional alterations in hippocampal subfields, and IR is a negative factor influencing the alteration of hippocampal subfields volume. These findings support the importance of IR in T2DM-MCI patients and might be potential neuroimaging biomarkers of cerebral impairment in T2DM-MCI patients.

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  • Intra-hippocampal INS induced long-term potentiation in the DG, and INS resistance negatively affects neuronal function especially in the DG.

    “Intra‐hippocampal INS induced long‐term potentiation in the DG, 15 and INS resistance negatively affects neuronal function especially in the DG. 72”

    From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [72]

    The citation to this paper is attached to the insulin-resistance clause, not the preceding long-term-potentiation claim. In the Discussion (page unavailable), the authors report reduced dentate-gyrus granule-cell-layer volume and propose that reduced insulin action may impair neurogenesis there. They do not directly establish that insulin resistance damages neuronal function, so the citing sentence states the proposed mechanism more firmly than the source does. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Yang, C., Zhang, H., Ma, Z., Fan, Y., Xu, Y., Tan, J., Tian, J., Cao, J., Zhang, W., Huang, G., & Zhao, L.
Affiliations
  • Gansu University of Traditional Chinese Medicine (CN)
  • Ningxia Medical University (CN)
  • Gansu Provincial Hospital (CN)
Corresponding author
Zhao, Lianping
ORCID
Venue
Journal of Diabetes
Publisher
Wiley
Published
2024-11
Volume
16
Issue
11
Pages
e70029-e70029
ISSN
  • 1753-0393 (ISSN-L)
  • 1753-0407
DOI
10.1111/1753-0407.70029
PMC
PMC11560383
OpenAlex
W4404327472
Cited by
11
References
4
Citations by year
2026: 4 · 2025: 6 · 2024: 1
FWCI
3.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Diabetes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (82360343)
  • Chinese Academy of Sciences (Young Scholars in Western China” project of the)
  • Natural Science Foundation of Gansu Province (20JR5RA156, 21JR7RA593)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
type 2 diabetes, mild cognitive impairment, insulin resistance, hippocampal subfields, hippocampal subiculum, hippocampal tail, hippocampal volume, functional connectivity, dorsolateral prefrontal cortex, anterior cingulate cortex, total cholesterol, triglycerides, fasting insulin, neuroimaging biomarkers
MeSH terms
Aged, Diabetes Mellitus, Type 2, Female, Hippocampus, Humans, Insulin Resistance, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prospective Studies, Cognitive Dysfunction

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