Evidence mapPaperPMID 41388643Full record

ArticleDiabetes, obesity & metabolism2026

Disentangling the relationship between glucose, insulin and brain health: A UK Biobank study.

Andrew C Mason, Nasri Fatih, Reecha Sofat, Christopher T Rentsch, Liam Smeeth, Krishnan Bhaskaran, Nish Chaturvedi, Victoria Garfield

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Article in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Andrew C MasonDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Nasri FatihUnit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
Reecha SofatUnit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
Christopher T RentschDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Liam SmeethDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Krishnan BhaskaranDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Nish ChaturvediUnit for Lifelong Health and Ageing, Institute of Cardiovascular Science, University College London, London, UK.
Victoria GarfieldDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.ORCID 0000-0002-5127-0890

Funding

Diabetes Research and Wellness Foundation SCA/01/NCF/22NIHR NIHR303160Wellcome TrustWellcome Trust 220283/Z/20/Z
6 · The paper itself

Abstract

backgroundGlycaemic traits are associated with poorer brain health and dementia risk. Recent advances in genetic instruments for specific glycaemic markers enable an in-depth investigation of the likely nature of associations and underlying mechanisms between diabetes-related mechanisms and brain health and dementia.

methodsWe used two-sample Mendelian randomisation (MR) in the UK Biobank (UKB) (maximum N = 357 883 White British, mean age 56.9 years, 54% female) applying inverse-variance weighted MR as our main estimator alongside MR-Egger, weighted median estimator (WME) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) as sensitivity tests. Instruments were 53 insulin resistance, 109 fasting glucose, 48 fasting insulin and 15 2-h post-load glucose genetic variants with variant-outcome effects estimated adjusting for 10 PCs. We checked core MR assumptions and sought to replicate results in an independent Alzheimer's dementia genome-wide association study (GWAS).

resultsIn UKB, higher 2-h post-load glucose was associated with a 69% increased Alzheimer's dementia risk (odds ratio 1.69 [95% confidence interval 1.38-2.07]), though this did not replicate in an independent GWAS. Fasting insulin, fasting glucose and postprandial glucose did not influence total brain, hippocampal or white-matter hyperintensity volumes. DISCUSSION: The association between elevated 2-h post-load glucose and increased Alzheimer's risk supports a potential role for postprandial hyperglycaemia in dementia. The lack of associations between fasting or postprandial glucose and hippocampal, total-brain or white matter hyperintensity volumes suggests this risk may operate independently of gross structural atrophy.

conclusionGenetically proxied postprandial hyperglycaemia contributes to increased Alzheimer's risk in mid-life, warranting replication in other populations and ancestries to confirm and clarify underlying mechanisms.

Indexed as

Alzheimer DiseaseBlood GlucoseBrainInsulinAgedBiological Specimen BanksFastingFemaleGenome-Wide Association StudyHumansInsulin ResistanceMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideUK BiobankBlood GlucoseInsulindementiaepidemiologygeneticsglycaemiaMendelian randomisation

Identifiers

PMID41388643
PMCPMC12890726

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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 Socratic graph.