Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression

van Sloten, Thomas T; Sedaghat, Sanaz; Carnethon, Mercedes R; Launer, Lenore J; Stehouwer, Coen D A

doi:10.1016/s2213-8587(19)30405-x

Cited by 702Neurological Disease Mechanisms and TreatmentsBarrier Structure and Function StudiesAcute Ischemic Stroke Management

Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression

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van Sloten, Thomas T, Sedaghat, Sanaz, Carnethon, Mercedes R, Launer, Lenore J, Stehouwer, Coen D A·2020·The Lancet Diabetes & Endocrinology

DOI 10.1016/s2213-8587(19)30405-xPMC PMC11044807

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Abstract

Adults with type 2 diabetes are at an increased risk of developing certain brain or mental disorders, including stroke, dementia, and depression. Although these disorders are not usually considered classic microvascular complications of diabetes, evidence is growing that microvascular dysfunction is one of the key underlying mechanisms. Microvascular dysfunction is a widespread phenomenon in people with diabetes, including effects on the brain. Cerebral microvascular dysfunction is also apparent in adults with prediabetes, suggesting that cerebral microvascular disease processes start before the onset of diabetes. The microvasculature is involved in the regulation of many cerebral processes that when impaired predispose to lacunar and haemorrhagic stroke, cognitive dysfunction, and depression. Main drivers of diabetes-related cerebral microvascular dysfunction are hyperglycaemia, obesity and insulin resistance, and hypertension. Increasing amounts of data from observational studies suggest that diabetes-related microvascular dysfunction is associated with a higher risk of stroke, cognitive dysfunction, and depression. Cerebral outcomes in diabetes might be improved following treatments targeting the pathways through which diabetes damages the microcirculation. These treatments might include drugs that reduce dicarbonyl compounds, augment cerebral insulin signalling, or improve blood-brain barrier permeability and cerebral vasoreactivity.

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Obesity and cardiometabolic comorbidities impair blood-brain barrier integrity.
“Obesity and cardiometabolic comorbidities impair BBB integrity [162]; thus, increased brain penetrability stands as a mechanism favoring neuroimmune activation, immune cell infiltration, and mood dysfunction.”
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“diometabolic comorbidities impair BBB integrity [162]; thus, increased brain penetrability stands as a mechanism favoring”
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Authors: van Sloten, T. T., Sedaghat, S., Carnethon, M. R., Launer, L. J., & Stehouwer, C. D. A.
Affiliations: Northwestern University (US)
National Institutes of Health (US)
Maastricht University Medical Centre (NL)
Corresponding author: Stehouwer, Coen D A
ORCID: Sedaghat, Sanaz
Carnethon, Mercedes R
Launer, Lenore J
Stehouwer, Coen D A
Venue: The Lancet Diabetes & Endocrinology
Publisher: Elsevier BV
Published: 2020-04
Volume: 8
Issue: 4
Pages: 325-336
ISSN: 2213-8587 (ISSN-L)
DOI: 10.1016/s2213-8587(19)30405-x
PMC: PMC11044807
OpenAlex: W3009656198
Cited by: 702
References: 100
Citations by year: 2026: 102 · 2025: 184 · 2024: 121 · 2023: 117 · 2022: 107 · 2021: 54 · 2020: 17
FWCI: 7.34
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: The Lancet Diabetes & Endocrinology (publishedVersion)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion, other-oa)
PubMed Central (acceptedVersion)
Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders: Dutch Heart Foundation (2018T025)
Topics: Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords: type 2 diabetes, cerebral microvascular dysfunction, stroke, cognitive impairment, depression, dementia, prediabetes, hyperglycemia, insulin resistance, obesity, hypertension, dicarbonyl compounds, blood-brain barrier permeability, cerebral vasoreactivity, lacunar stroke, hemorrhagic stroke
MeSH terms: Cerebrovascular Circulation, Depression, Diabetes Mellitus, Type 2, Humans, Hypertension, Microcirculation, Stroke, Cognitive Dysfunction

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Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression

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