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Cited by 28Dementia and Cognitive Impairment ResearchDiabetes Treatment and ManagementDiabetes Management and Research

Association between glycated hemoglobin A1c levels, control status, and cognitive function in type 2 diabetes: a prospective cohort study

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Xiao, Yanhua, Hong, Xuezhi, Neelagar, Ranjana, Mo, Hanyou·2025·Scientific Reports
DOI 10.1038/s41598-025-89374-6PMC PMC11811129
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Abstract

Cognitive impairment (CI) is a common complication in patients with type 2 diabetes mellitus (T2DM), but its relationship with long-term glycemic control remains unclear. This study aimed to investigate the associations between mean hemoglobin A1c (HbA1c) levels, HbA1c control status, HbA1c fluctuations, and CI in Chinese adults aged 45 years and older with T2DM using data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 797 participants with HbA1c measurements from 2011 to 2015 and cognitive function assessments in 2018 were included. Logistic regression models and restricted cubic spline (RCS) analysis were applied, adjusting for potential confounders. Higher mean HbA1c levels (≥ 9%) were significantly associated with an increased risk of CI, particularly in global cognition and episodic memory (OR 4.03 (1.45-11.20) for global cognition; OR 2.92 (1.02-8.38) for episodic memory). RCS analysis revealed a U-shaped relationship between mean HbA1c and CI, indicating that both excessively low and high HbA1c levels elevate CI risk. Uncontrolled HbA1c levels (≥ 8%) were also linked to higher CI risk compared to stable HbA1c levels. Maintaining HbA1c levels below 8% may significantly reduce CI risk in T2DM patients, highlighting the importance of personalized glycemic management.

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  • Longer duration of diabetes is associated with worsening cognitive function.

    “Both hyperglycemia and hypoglycemia are associated with a decline in cognitive function (22,23), and longer duration of diabetes is associated with worsening cognitive function.”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [22]

    The Discussion reports that people with both longer diabetes duration and poor glycemic control had higher dementia risk than those with shorter duration and better control. It also says prior studies suggest duration may contribute to cognitive-impairment risk, but this study could not examine duration. The source therefore does not establish the unqualified association between duration alone and worsening cognitive function. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Both hyperglycemia and hypoglycemia are associated with a decline in cognitive function.

    “Both hyperglycemia and hypoglycemia are associated with a decline in cognitive function (22,23), and longer duration of diabetes is associated with worsening cognitive function.”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [22]

    The Discussion links sustained hyperglycemia to cognitive impairment and says hypoglycemic episodes can exacerbate brain injury. But it does not establish the claimed association between hypoglycemic episodes and cognitive decline; the Results report no significant association for lower mean HbA1c levels in the fully adjusted model. Page numbers were not provided in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Xiao, Y., Hong, X., Neelagar, R., & Mo, H.
Affiliations
  • First Affiliated Hospital of GuangXi Medical University (CN)
  • Düsseldorf University Hospital (DE)
Corresponding author
Mo, Hanyou
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2025-02-11
Volume
15
Issue
1
Pages
5011-5011
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-025-89374-6
PMC
PMC11811129
OpenAlex
W4407310933
Cited by
28
References
5
Citations by year
2026: 19 · 2025: 9
FWCI
18.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Clinical Research “Climbing” Program of the First Affiliated Hospital of Guangxi Medical University (YYZS2023005)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 2 diabetes, HbA1c, cognitive impairment, glycemic control, episodic memory, global cognition, U-shaped relationship, older adults
MeSH terms
Glycemic Control, Aged, China, Cognition, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Risk Factors, Cognitive Dysfunction

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