Phenotypic heterogeneity of type 2 diabetes and risks of complications with a tree-like representation
Authors' conclusion
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.
Study context
- Population
- Individuals with newly diagnosed T2D, UK Biobank
- Participants
- 6,406 individuals
- Outcome
- Disease risk patterns across DDRTree-derived phenotypic structure
Methodological detailsDiscriminative dimensionality reduction with trees (DDRTree) algorithm on seven clinical variables, competing risk models, proteomic analyses, external cohort: Dongfeng-Tongji Diabetes cohort, An online tool was provided for individual risk prediction
- DDRTree algorithm on seven clinical variables
- Competing risk models
- Proteomic analyses
- External cohort: Dongfeng-Tongji Diabetes cohort
- An online tool was provided for individual risk prediction
Main finding
As reported in the abstract
- All seven clinical variables formed a gradient distribution across the phenotypic structure, revealing three distinct disease risk patterns
- Adiposity, hypertension and dyslipidemia: elevated risks of macrovascular complications, DKD, Parkinson’s disease and NAFLD
- Hyperglycemia and dyslipidemia: higher risks of MI, diabetic neuropathy, DR, depression and chronic obstructive pulmonary disease
- Elevated total cholesterol and HDL-C: increased risks of cancer and Alzheimer’s disease
Observational data: associations, not effects.
Further findings
Proteomic pathways
- Pattern-specific pathways: metabolic dysregulation and extracellular matrix remodeling (first); inflammatory activation and lipid metabolism alterations (second); immune activation with chemical carcinogenesis (third)
Lifestyle factors
- Sensitivity to lifestyle factors was phenotype-specific
Replication in Dongfeng-Tongji Diabetes cohort
- Patterns similar, though CVD and retinopathy risks strongly associated with hypertension
Original publication
Phenotypic heterogeneity of type 2 diabetes and risks of complications with a tree-like representation. Cardiovasc Diabetol. Published 30 March 2026. doi:10.
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