Metabolomic Profiles Associated with BMI, Waist Circumference, and Diabetes and Inflammation Biomarkers in Women

Objective: This study was undertaken to identify metabolites associated with BMI and waist circumference (WC) in women and to determine whether these metabolites are associated with biomarkers of metabolic health. Methods: Untargeted metabolomic analysis was done on serum from 1,534 women. Metabolites associated with BMI and WC were identified using linear regression with a Bonferroni-corrected P value. Clustered blocks of these metabolites were then defined whose association with the anthropometric measures could be represented by a single metabolite. The association of these representative metabolites with biomarkers for diabetes and inflammation was then determined. Results: About one-third of 781 metabolites included in the analyses were associated with BMI and/or WC. Associations were found for some novel metabolites, including several sphingolipids, nucleotides, and modified fatty acids. Among metabolites most strongly inversely associated with BMI, the choline-containing plasmalogen (O-16:0/18:1) (β = −0.30, P = 6.62 × 10⁻³²) was also inversely associated with c-peptide and positively associated with adiponectin. Adjustment for BMI attenuated the metabolite-biomarker associations more for hemoglobin A1c (> 100%) and c-peptide (58.8% to > 100%) than for C-reactive protein (10.5%-40.0%) and adiponectin (7.0%-30.4%). Conclusions: These results add to the list of metabolites associated with adiposity and indicate that some may influence processes that contribute to the development of obesity-related diseases.