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Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes
Jun Li, Jie Hu, Huan Yun, Zhendong Mei, Xingyan Wang, Kai Luo, Marta Guasch‐Ferré, Xikun Han et al.. Nature Medicine, 2026-01-14
Topic: Risk, prevention and care in population studies
The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including insulin resistance, glucose/insulin response, ectopic fat deposition, energy/lipid regulation and liver function. Lifestyle factors—particularly physical activity, obesity and diet—explained greater variations in T2D-associated versus non-associated metabolites, with specific metabolites revealed as potential mediators. Finally, a 44-metabolite signature improved T2D risk prediction beyond conventional factors. These findings provide a foundation for understanding T2D mechanisms and may inform precision prevention targeting specific metabolic pathways. Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Li, J., Hu, J., Yun, H., Mei, Z., Wang, X., Luo, K., et al. (2026). Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes. Nature Medicine. https://doi.org/10.1038/s41591-025-04105-8
Vancouver
Li J, Hu J, Yun H, Mei Z, Wang X, Luo K, et al. Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes. Nature Medicine. 2026. doi:10.1038/s41591-025-04105-8. PMID: 41535386.
BibTeX
@article{li2026-41535386,
author = {Li, Jun and Hu, Jie and Yun, Huan and Mei, Zhendong and Wang, Xingyan and Luo, Kai and Guasch‐Ferré, Marta and Han, Xikun and others},
title = {{Circulating metabolites, genetics and lifestyle factors in relation to future risk of type 2 diabetes}},
journal = {Nature Medicine},
year = {2026},
doi = {10.1038/s41591-025-04105-8},
pmid = {41535386},
url = {https://doi.org/10.1038/s41591-025-04105-8}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized.
- Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways.
- Lifestyle factors—particularly physical activity, obesity and diet—explained greater variations in T2D-associated versus non-associated metabolites, with specific metabolites revealed as potential mediators.
- These findings provide a foundation for understanding T2D mechanisms and may inform precision prevention targeting specific metabolic pathways.
- They identified 235 metabolites associated with future risk of type 2 diabetes (T2D).
Why it matters
This study is about blood metabolites and type 2 diabetes risk, not Alzheimer's disease, so it offers no information on Alzheimer's treatment, cure or prevention. It identified many metabolites linked to future type 2 diabetes and a metabolite signature that improved risk prediction.
New to this subject? Start with our plain-English guide: Prevention →
Study details
- Participants23,000
- Evidence strengthLow
How this study scored 57/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 23,000 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 | 2 / 7 | Cited 14 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 27.1× 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 | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author QIBIN QI: h-index 2 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 37 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41535386) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-025-04105-8
- PubMed: 41535386
- Original source →
- Free full text: Nature Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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