Integrative Metabolomics of Targeted and Nontargeted Analyses in T2D Progression
Authors' conclusion
Energy metabolism shifts occur early, while amino acid alterations emerge later stages. These stage-specific signatures may guide diabetes prevention strategies.
Study context
- Population
- KORA cohort; 104 targeted and 312 nontargeted metabolites profiled at baseline (S4) and follow-ups (F4, FF4)
- Participants
- 8,240 observations
- Exposure
- NORM vs PreT2D vs T2D glycemic states
- Outcome
- Metabolites characterizing progression from NORM to PreT2D (early) and PreT2D to T2D (late)
- Follow-up
- 14 years
Methodological detailstargeted and nontargeted metabolomics, three time points over 14 years, linear mixed-effects models, mediation analysis, Mendelian randomization
- Targeted and nontargeted metabolomics
- Three time points over 14 years
- Linear mixed-effects models
- Mediation analysis
- Mendelian randomization
Main finding
As reported in the abstract
Bonferroni-significant metabolites (45 targeted, 109 nontargeted, 14 overlapping)
140
Early-stage metabolites (significant in PreT2D/T2D vs NORM), mainly energy metabolism markers: fatty acid oxidation (e.g., 37 lipids) and TCA cycle (e.g., citrate)
68
Late-stage metabolites (significant in T2D vs PreT2D/NORM), incl. Branched-chain amino acids (BCAAs) and γ-glutamyl derivatives
20
Observational data: associations, not effects.
Further findings
Incident cases (trajectory analysis of 1,050 individuals: 211 incident PreT2D, 112 incident T2D)
- Fewer significant associations in incident cases
Sensitivity models (additionally adjusted for glycemic and cardiovascular factors)
- Early-stage metabolites validated
- 50%
- Late-stage metabolites not validated
Mediation of γ-glutamyl-valine–T2D association by fasting glucose
- Proportion mediated by fasting glucose
- 35.1%
MR analysis
- No causal roles for C2, BCAAs or γ-glutamyl-valine
Original publication
Composed by AI from the published abstract and checked against it. How Briefs are made →