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Disentangling the relationship between glucose, insulin and brain health: A UK Biobank study
Andrew C. Mason, Nasri Fatih, Reecha Sofat, Christopher T. Rentsch, Liam L Smeeth, Krishnan Bhaskaran, Nish Chaturvedi, Victoria Garfield. Diabetes Obesity and Metabolism, 2025-12-12
Topic: Brain proteins, microglia and lab models
In 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. 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. Genetically 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.
Key findings
- In 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.
- 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.
- Genetically 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.
Why it matters
This study found that higher 2-hour post-load glucose was associated with increased Alzheimer's dementia risk, though this did not replicate in an independent analysis, and fasting insulin, fasting glucose, and postprandial glucose did not influence brain volumes. It suggests that postprandial hyperglycaemia may play a role in Alzheimer's risk, but it does not show that controlling glucose prevents dementia.
Study details
- Participants357
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Diabetes Obesity and Metabolism) |
| Journal's citation record | 2 / 4 | Diabetes Obesity and Metabolism: journal h-index 186 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 357 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Victoria Garfield: h-index 21 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41388643) |
| Free to read | 2 / 2 | Free to read |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1111/dom.70353
- PubMed: 41388643
- Original source →
- Free full text: Diabetes Obesity and Metabolism →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Mason, A. C., Fatih, N., Sofat, R., Rentsch, C. T., Smeeth, L. L., Bhaskaran, K., et al. (2025). Disentangling the relationship between glucose, insulin and brain health: A UK Biobank study. Diabetes Obesity and Metabolism. https://doi.org/10.1111/dom.70353
Vancouver
Mason AC, Fatih N, Sofat R, Rentsch CT, Smeeth LL, Bhaskaran K, et al. Disentangling the relationship between glucose, insulin and brain health: A UK Biobank study. Diabetes Obesity and Metabolism. 2025. doi:10.1111/dom.70353. PMID: 41388643.
BibTeX
@article{mason2025-41388643,
author = {Mason, Andrew C. and Fatih, Nasri and Sofat, Reecha and Rentsch, Christopher T. and Smeeth, Liam L and Bhaskaran, Krishnan and Chaturvedi, Nish and Garfield, Victoria},
title = {{Disentangling the relationship between glucose, insulin and brain health: A UK Biobank study}},
journal = {Diabetes Obesity and Metabolism},
year = {2025},
doi = {10.1111/dom.70353},
pmid = {41388643},
url = {https://doi.org/10.1111/dom.70353}
}
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