Plasma Metabolome, Long-term Body Weight Change, and Type 2 Diabetes in U.S. Individuals

Area of Science:

• Metabolomics
• Endocrinology
• Preventive Medicine

Background:

• Body weight significantly influences the blood metabolome.
• Understanding plasma metabolomic profiles' predictive power for long-term weight change is crucial.
• Associations between metabolites, weight change, and incident type 2 diabetes (T2D) require further investigation.

Purpose of the Study:

• To investigate associations among plasma metabolites, current weight, and weight change trajectories.
• To examine the relationship between plasma metabolomic profiles and incident T2D in adults.
• To determine if metabolomic profiles predict future weight change and T2D risk.

Main Methods:

• 260 plasma metabolites were profiled in 7,499 U.S. health professionals.
• A metabolomic score predicting body mass index (BMI) change was developed using elastic net regression.
• Multivariable Cox models were used to assess associations with incident T2D.

Main Results:

• Metabolomic predictors of BMI change varied by baseline weight status (lean, overweight, obese).
• Lean individuals had more significant metabolite predictors (46) compared to overweight (20) and obese (13) groups.
• The derived metabolomic score was associated with higher T2D risk in lean and overweight individuals, but not in the obese group.

Conclusions:

• Plasma metabolomic profiles predicting future weight change are distinct across different body weight statuses.
• Specific metabolic signatures may identify lean individuals at elevated risk for future weight gain and T2D.
• These findings offer potential for earlier, targeted prevention strategies for weight gain and T2D.