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Phenotypic heterogeneity of type 2 diabetes and risks of complications with a tree-like representation
Jiajing Che, Xianli Li, Zixin Qiu, Ruyi Li, Hancheng Yu, Jinchi Xie, Tianyu Guo, Zijun Tang et al.. Cardiovascular diabetology, 2026-03-30
Topic: Genetics and APOE
This study included 6406 individuals with newly diagnosed type 2 diabetes from the UK Biobank. All seven clinical variables formed a gradient distribution across the DDRTree-derived phenotypic structure, revealing three distinct disease risks patterns: participants with adiposity, hypertension and dyslipidemia exhibited elevated risks of macrovascular complications, diabetic kidney disease, Parkinson’s disease and non-alcohol fatty liver disease; those with hyperglycemia and dyslipidemia had higher risks of myocardial infarction, diabetic neuropathy, diabetic retinopathy, depression and chronic obstructive pulmonary disease; while elevated total cholesterol and high-density lipoprotein cholesterol were associated with increased risks of cancer and Alzheimer’s disease. Proteomic analyses identified pattern-specific pathways: metabolic dysregulation and extracellular matrix remodeling in the first pattern, inflammatory activation and lipid metabolism alterations in the second, and immune activation with chemical carcinogenesis in the third. Furthermore, sensitivity to lifestyle factors were phenotypic-specific. These patterns were similar in the Dongfeng-Tongji Diabetes cohort, though cardiovascular disease and retinopathy risks were strongly associated with hypertension. An online tool was provided for individual risk prediction. Our findings reveal distinct spatial distributions of clinical features and associated disease risks in type 2 diabetes, with subgroups exhibiting unique proteomic signatures and differential lifestyle responses, underscoring the importance for personalized management for diabetes care.
Key findings
- This study included 6406 individuals with newly diagnosed type 2 diabetes from the UK Biobank.
- All seven clinical variables formed a gradient distribution across the DDRTree-derived phenotypic structure, revealing three distinct disease risks patterns: participants with adiposity, hypertension and dyslipidemia exhibited elevated risks of macrovascular complications, diabetic kidney disease, Parkinson’s disease and non-alcohol fatty liver disease; those with hyperglycemia and dyslipidemia had higher risks of myocardial infarction, diabetic neuropathy, diabetic retinopathy, depression and chronic obstructive pulmonary disease; while elevated total cholesterol and high-density lipoprotein cholesterol were associated with increased risks of cancer and Alzheimer’s disease.
- Proteomic analyses identified pattern-specific pathways: metabolic dysregulation and extracellular matrix remodeling in the first pattern, inflammatory activation and lipid metabolism alterations in the second, and immune activation with chemical carcinogenesis in the third.
- Furthermore, sensitivity to lifestyle factors were phenotypic-specific.
- These patterns were similar in the Dongfeng-Tongji Diabetes cohort, though cardiovascular disease and retinopathy risks were strongly associated with hypertension.
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Study details
- Participants6,406
- Evidence strengthModerate
How this study scored 59/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 33 of the 56 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cardiovascular diabetology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 3 / 4 | 6,406 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41913207) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 33 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 33 of the 56 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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APA 7th
Che, J., Li, X., Qiu, Z., Li, R., Yu, H., Xie, J., et al. (2026). Phenotypic heterogeneity of type 2 diabetes and risks of complications with a tree-like representation. Cardiovascular diabetology. https://doi.org/10.1186/s12933-026-03147-7
Vancouver
Che J, Li X, Qiu Z, Li R, Yu H, Xie J, et al. Phenotypic heterogeneity of type 2 diabetes and risks of complications with a tree-like representation. Cardiovascular diabetology. 2026. doi:10.1186/s12933-026-03147-7. PMID: 41913207.
BibTeX
@article{che2026-41913207,
author = {Che, Jiajing and Li, Xianli and Qiu, Zixin and Li, Ruyi and Yu, Hancheng and Xie, Jinchi and Guo, Tianyu and Tang, Zijun and others},
title = {{Phenotypic heterogeneity of type 2 diabetes and risks of complications with a tree-like representation}},
journal = {Cardiovascular diabetology},
year = {2026},
doi = {10.1186/s12933-026-03147-7},
pmid = {41913207},
url = {https://doi.org/10.1186/s12933-026-03147-7}
}