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Cited by 46Diabetes Management and ResearchDementia and Cognitive Impairment ResearchDiabetes Treatment and Management

Association between hypoglycemia and dementia in patients with diabetes: a systematic review and meta-analysis of 1.4 million patients

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Huang, Lifen, Zhu, Manlian, Ji, Jie·2022·Diabetology & Metabolic Syndrome
DOI 10.1186/s13098-022-00799-9PMC PMC8842524
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Abstract

Background: Diabetes mellitus (DM) is known to be a risk factor for dementia. However, it is unclear if hypoglycemic events play a role in the risk of dementia. We aimed to systematically review evidence on the risk of dementia in DM patients based on prior hypoglycemic events. Methods: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched till 15th November 2021 for cohort studies assessing the risk of dementia based on prior hypoglycemic events in DM patients. Adjusted data were pooled in a random-effects model. Results: Ten studies with a total of 1,407,643 patients were included. Pooled analysis of all ten studies indicated that hypoglycemic episodes were associated with a statistically significant increase in the risk of dementia in DM patients as compared to those not experiencing hypoglycemic episodes (HR: 1.44 95% CI: 1.26, 1.65 I 2 = 89% p < 0.00001). The results did not change on the exclusion of any study. Sub-group analysis based on the study population, type of study, adjustment for glycated hemoglobin, gender, and the number of hypoglycemic episodes also presented similar results. Conclusions: Evidence from observational studies with a large sample size indicates that DM patients with hypoglycemic episodes are at increased risk of dementia. Anti-hyperglycemic drugs should be adequately tailored in these patients to avoid the risk of dementia.

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  • Diabetes-related dementia is characterized by slower progression of dementia, absence of typical neuroimaging findings, advanced age, elevated A1C levels, long duration of diabetes, high frequency of insulin use, frailty, sarcopenia, and dynapenia.

    “Diabetes-related dementia is characterized by a slower progression of dementia, absence of typical neuroimaging findings, advanced age, elevated A1C levels, long duration of diabetes, high frequency of insulin use, frailty, sarcopenia, and dynapenia (loss of muscle strength not caused by neurologic or muscular diseases) (18).”

    From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [18]

    The Discussion reports that high HbA1c is associated with increased dementia risk in people with diabetes, supporting the elevated-A1C element. It does not describe diabetes-related dementia as a syndrome with slower progression, absent typical neuroimaging findings, advanced age, long diabetes duration, frequent insulin use, frailty, sarcopenia, or dynapenia; its focus is hypoglycemia and dementia risk. (LLM, conf=0.82)

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  • 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 [23]

    The Background says severe hypoglycemia can impair cognitive function, and the Discussion reports an association between hypoglycemic events and dementia risk. The Discussion also links high blood-sugar markers to dementia risk, but says the role of long-term glucose control in cognitive decline is unclear and notes that a trial found no significant difference in clinical cognitive decline. Thus the paper does not establish the claim about hyperglycemia and declining cognitive function as broadly as stated. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Diabetes-related dementia is characterized by slower progression of dementia, absence of typical neuroimaging findings, advanced age, elevated A1C levels, long duration of diabetes, high frequency of insulin use, frailty, sarcopenia, and dynapenia.

    “Diabetes-related dementia is characterized by a slower progression of dementia, absence of typical neuroimaging findings, advanced age, elevated A1C levels, long duration of diabetes, high frequency of insulin use, frailty, sarcopenia, and dynapenia (loss of muscle strength not caused by neurologic or muscular diseases) (23).”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [23]

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  • Diabetes-related dementia is emerging as distinct from Alzheimer disease and vascular dementia.

    “A newly recognized clinical entity, diabetes-related dementia, is emerging as distinct from Alzheimer disease and vascular dementia.”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [23]

    The Background and Discussion describe an increased risk of dementia in people with diabetes, and the Conclusions address dementia risk after hypoglycemic events. No passage in our copy identifies diabetes-related dementia as a newly recognized clinical entity or distinguishes it from Alzheimer disease and vascular dementia (searched for those terms and the claimed distinction). (LLM, conf=0.74)

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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 [23]

    The Results (Study details; page unavailable) list diabetes duration as a variable adjusted for in some included studies, but give no finding linking longer duration to worsening cognitive function. The Discussion addresses glycemic control and dementia risk, not that duration-specific association (searched: longer duration of diabetes; diabetes duration and cognitive decline). (LLM, conf=0.76)

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Cites

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Research works printed but not linked: 26

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Cited by

Sorted by citations

Authors
Huang, L., Zhu, M., & Ji, J.
Corresponding author
Ji, Jie
ORCID
Ji, Jie
Venue
Diabetology & Metabolic Syndrome
Publisher
Springer Science and Business Media LLC
Published
2022-02-14
Volume
14
Issue
1
Pages
31-31
ISSN
1758-5996 (ISSN-L)
DOI
10.1186/s13098-022-00799-9
PMC
PMC8842524
OpenAlex
W4213092625
Cited by
46
References
7
Citations by year
2026: 8 · 2025: 15 · 2024: 13 · 2023: 6 · 2022: 4
FWCI
1.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetology & Metabolic Syndrome (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
hypoglycemia, dementia, diabetes mellitus, hypoglycemic episodes, dementia risk, HbA1c, anti-hyperglycemic drugs, antidiabetic drug selection

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