Integrative metabolomic and proteomic analysis of diabetic kidney disease progression with younger‐onset type 2 diabetes
Authors' conclusion
Lower plasma BCAA levels are independently associated with DKD progression in YT2D. Integrative multi-omics analysis highlights disruptions in metabolic and apoptotic pathways, providing insights into DKD pathophysiology and potential biomarkers for early risk stratification.
Study context
- Population
- YT2D patients (diagnosed at ≤ age 40), multi-ethnic Asian cohort; plasma metabolites by nuclear magnetic resonance spectroscopydiscovery 550, validation 237
- Participants
- 787 patients
- Exposure
- Diabetic kidney disease (DKD) progressors vs non-progressors
- Outcome
- DKD progression: annual decline in eGFR of ≥3 mL/min/1.73 m² or ≥ 40% reduction in eGFR from baseline
- Follow-up
- Median 5.7 years
Methodological detailsmulti-ethnic Asian cohort, discovery and internal validation cohorts, integrative metabolomic-proteomic analysis (sparse partial least squares discriminant analysis (sPLS-DA))
- Multi-ethnic Asian cohort
- Discovery and internal validation cohorts
- Integrative metabolomic-proteomic analysis (sPLS-DA)
Main finding
As reported in the abstract
Metabolites differentially expressed between DKD progressors and non-progressors
98
Total branched-chain amino acids (BCAAs), OR
0.60 (0.46-0.79) (95% CI)
Valine, OR
0.62 (0.48-0.81) (95% CI)
Leucine, OR
0.56 (0.43-0.74) (95% CI)
Observational data: associations, not effects.
Further findings
Integrative metabolomic-proteomic analysis (n = 428): prediction of DKD progression
- Three components comprising 23 proteins and 30 metabolites, involved in citrate cycle and apoptosis, improved prediction beyond clinical risk factors; AUC
- 0.69-0.83
- sPLS-DA
Original publication
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