Serum Metabolomic Profiling of Incident Type 2 Diabetes Mellitus in the Multi-ethnic Study of Atherosclerosis and Rotterdam Study
Authors' conclusion
1H NMR measured metabolites involved in aminoacyl-tRNA biosynthesis, BCAA metabolism, glycolysis/gluconeogenesis, and glycerolipid metabolism were significantly associated with incident T2DM and provided modest to moderate predictive utility beyond traditional risk factors.
Study context
- Population
- Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Rotterdam Study (RS)
- Participants
- 3,460 vs 1,556
- Exposure
- MESA vs RS
- MESAn = 3,460
- RSn = 1,556
- Outcome
- Serum metabolomic biomarkers associated with incident T2D
Methodological detailsuntargeted 1H NMR metabolomics, discovery and replication cohorts, 2-sample Mendelian randomization
- Untargeted 1H NMR metabolomics
- Discovery and replication cohorts
- 2-sample Mendelian randomization
Main finding
As reported in the abstract
Metabolites associated with incident T2D
- Metabolites significantly associated with incident T2D
- 19
Observational data: associations, not effects.
Further findings
Δ C-statistic
| Outcome | MESA | RS |
|---|---|---|
| Improvement in T2D risk prediction adding replicated metabolites to Framingham Diabetes Risk Score (Δ C-statistic) | 0.05 (95% CI 0.04–0.07) | 0.03 (95% CI 0.01–0.05) |
Network analyses
- Interactions with upstream regulators incl. p38 MAPK, JNK and mTOR signaling pathways
Mendelian randomization
- Genetically increased branched-chain amino acids (BCAAs) and mannose were associated with T2D
Original publication
Serum Metabolomic Profiling of Incident Type 2 Diabetes Mellitus in the Multi-ethnic Study of Atherosclerosis and Rotterdam Study. J Clin Endocrinol Metab. Published 20 November 2024. doi:10.
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