Home › Research › Prevention and risk
Metabolomic signatures of data-driven type 2 diabetes subtypes and their associations with dementia and stroke risk
Han, S.; Hewett, J.; Ahmadizar, F.; Biessels, G. J.. medRxiv (preprint), 2026-08-25
Topic: Brain proteins, microglia and lab models
We examined whether their metabolomic profiles also differed and whether subtype-related metabolic patterns were associated with dementia, stroke, and all-cause mortality. The VLDL/LDL-enriched PC was inversely associated with mortality (HR 0.93, 95% CI 0.88-0.98). No significant stroke results were observed. Adjustment for the PCA-derived metabolomic patterns generally attenuated subtype-outcome associations, MR analyses identified 197 metabolite-outcome associations that remained significant after FDR correction. ConclusionsMetabolomic profiling showed that the metabolic signatures differed across data-driven T2D subtypes and highlighted lipid and lipoprotein remodeling as a major metabolic feature associated with dementia, stroke, and all-cause mortality. What is novel about this study?This study integrates comprehensive NMR metabolomics with data-driven T2D subtypes to identify metabolic patterns associated with dementia, stroke, and mortality. Rather than focusing on individual metabolites, we identified biologically interpretable metabolomic patterns and showed that differences in lipid and lipoprotein composition were prominent features of subtype heterogeneity and long-term outcome risk. Metabolomic signatures reflecting high-density lipoprotein (HDL) remodeling and lipoprotein composition were consistently associated with dementia, stroke, and all-cause mortality. C_LIO_LIHDL patterns were associated with dementia, stroke, and all-cause mortality.
Key findings
- We examined whether their metabolomic profiles also differed and whether subtype-related metabolic patterns were associated with dementia, stroke, and all-cause mortality.
- The VLDL/LDL-enriched PC was inversely associated with mortality (HR 0.93, 95% CI 0.88-0.98).
- No significant stroke results were observed.
- Adjustment for the PCA-derived metabolomic patterns generally attenuated subtype-outcome associations, MR analyses identified 197 metabolite-outcome associations that remained significant after FDR correction.
- ConclusionsMetabolomic profiling showed that the metabolic signatures differed across data-driven T2D subtypes and highlighted lipid and lipoprotein remodeling as a major metabolic feature associated with dementia, stroke, and all-cause mortality.
Why it matters
This study found that metabolomic signatures differed across data-driven type 2 diabetes subtypes, with lipid and lipoprotein patterns associated with dementia, stroke and all-cause mortality, and no significant stroke results. These are observational associations that may inform risk understanding, not a treatment or cure.
New to this subject? Start with our plain-English guide: Prevention →
Study details
- Participants7,671
- Effect size76.7%; HR 1.17; HR 1.18
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 31 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 29 of the 94 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 7,671 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Fariba Ahmadizar: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Utrecht University: institution h-index 1,157 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 29 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 29 of the 94 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
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. Check the citation against the original before you use it.
APA 7th
Han, S., Hewett, J., Ahmadizar, F., & Biessels, G. J. (2026). Metabolomic signatures of data-driven type 2 diabetes subtypes and their associations with dementia and stroke risk. medRxiv (preprint). https://doi.org/10.64898/2026.08.21.26361082
Vancouver
Han S, Hewett J, Ahmadizar F, Biessels GJ. Metabolomic signatures of data-driven type 2 diabetes subtypes and their associations with dementia and stroke risk. medRxiv (preprint). 2026. doi:10.64898/2026.08.21.26361082.
BibTeX
@article{han2026-6bbe6bcc,
author = {Han, S. and Hewett, J. and Ahmadizar, F. and Biessels, G. J.},
title = {{Metabolomic signatures of data-driven type 2 diabetes subtypes and their associations with dementia and stroke risk}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.21.26361082},
url = {https://doi.org/10.64898/2026.08.21.26361082}
}
Related studies in Prevention and risk
Also tagged “biobank”
1,084 studies in the library carry the topic tag “biobank”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,084 tagged studies.