Unveiling biomarkers via plasma metabolome profiling for diabetic macrovascular and microvascular complications
Authors' conclusion
These findings may serve as potential biomarkers for predicting the development of vascular complications in patients with diabetes, thereby improving clinical management strategies for affected patients.
Study context
- Population
- Patients with diabetes, UK Biobank and FinnGen Biobank; 249 nuclear magnetic resonance (NMR)-quantified plasma metabolites7,711 with diabetes
- Participants
- 333,870 patients
- Outcome
- Incident macrovascular (HF, stroke, CHD) and microvascular (DN, kidney disease, retinopathy) complications
Methodological detailslongitudinal, NMR metabolomics, Least Absolute Shrinkage and Selection Operator-Cox (LASSO-Cox) regression, multivariate Cox proportional hazards regression, bidirectional two-sample Mendelian randomization
- Longitudinal
- NMR metabolomics
- LASSO-Cox regression
- Multivariate Cox proportional hazards regression
- Bidirectional two-sample Mendelian randomization
Main finding
As reported in the abstract
Metabolites associated with incident complications (multivariate Cox)
- Macrovascular: creatinine HR
- 1.32, 95% CI 1.17-1.50, P < 0.001
- Macrovascular: albumin HR
- 0.87, 95% CI 0.81-0.94, P < 0.001
- Macrovascular: tyrosine HR
- 0.91, 95% CI 0.85-0.96, P = 0.001
- Macrovascular: glutamine HR
- 1.08, 95% CI 1.01-1.15, P = 0.020
- Macrovascular: lactate HR
- 1.07, 95% CI 1.01-1.14, P = 0.023
- Macrovascular: phospholipids to total lipids in small low-density lipoprotein (LDL) HR
- 1.10, 95% CI 1.01-1.19, P = 0.023
- Microvascular: glucose HR
- 1.25, 95% CI 1.18-1.33, P < 0.001
- Microvascular: tyrosine HR
- 0.86, 95% CI 0.80-0.92, P < 0.001
- Microvascular: very large HDL particle concentration HR
- 0.78, 95% CI 0.68-0.90, P = 0.001
- Microvascular: valine HR
- 1.21, 95% CI 1.08-1.36, P = 0.001
- Microvascular: free cholesterol to total lipids in very small very low-density lipoprotein (VLDL) HR
- 1.28, 95% CI 1.10-1.49, P = 0.001
- Microvascular: alanine HR
- 1.08, 95% CI 1.01-1.15, P = 0.022
- Microvascular: albumin HR
- 0.92, 95% CI 0.86-0.99, P = 0.027
- Microvascular: isoleucine HR
- 0.89, 95% CI 0.80-1.00, P = 0.041
Observational data: associations, not effects.
Further findings
Incident complications · follow-up 13.06 ± 3.59 years (macro); 12.77 ± 3.90 years (micro)
- Developed macrovascular complications
- 1,457
- Developed microvascular complications
- 1,635
Mendelian randomization (MR): CHD
- Phospholipids to total lipids in small LDL, OR
- 1.96, 95% CI 1.33-2.88, P = 0.015
Reverse MR: DN
- Docosahexaenoic acid to total fatty acids, OR
- 0.97, 95% CI 0.95-0.99, P = 0.019
- Triglycerides to total lipids in very large VLDL, OR
- 1.03, 95% CI 1.01-1.05, P = 0.019
- Pyruvate, OR
- 1.03, 95% CI 1.01-1.05, P = 0.046
Original publication
Unveiling biomarkers via plasma metabolome profiling for diabetic macrovascular and microvascular complications. Cardiovasc Diabetol. Published 18 August 2025. doi:10.
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