Plasma Metabolome, Long-term Body Weight Change, and Type 2 Diabetes in U.S. Individuals
Authors' conclusion
Plasma metabolomic profiles predictive of future weight change differ by body weight status. Distinct metabolic signatures may help identify certain lean individuals at an elevated risk of future weight gain and T2D, offering opportunities for earlier, more targeted prevention.
Study context
- Population
- U.S. health professionals; 260 plasma metabolites profiled
- Participants
- 7,499 professionals
- Exposure
- Metabolomic score of BMI change by baseline weight status
- Outcome
- Metabolites significantly predicting BMI change slope, by baseline weight status
Methodological detailsmetabolomic analysis, elastic net regression with training/testing approach, multivariable Cox models
- Metabolomic analysis
- Elastic net regression with training/testing approach
- Multivariable Cox models
Main finding
As reported in the abstract
Lean
46 metabolites
Overweight
20
Obesity
13
Observational data: associations, not effects.
Further findings
| Outcome | Lean | Overweight | Obesity |
|---|---|---|---|
| Correlation of lean-derived metabolomic score with BMI slope | Spearman r 0.31 | r 0.16 | r 0.10 |
Incident T2D per 1 SD of metabolomic score
| Population | Estimate | |
|---|---|---|
| Lean | HR per 1 SD 1.42 (95% CI 1.26-1.60) | |
| Overweight | HR 1.29 (95% CI 1.17-1.42) | |
| 0.512Ratio (log scale) |
- Score not associated with T2D risk in obesity
Original publication
Plasma Metabolome, Long-term Body Weight Change, and Type 2 Diabetes in U.S. Individuals. Diabetes Care. Published 13 August 2025. doi:10.
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