Abstract P497: Saliva, Plasma, and Multi-Fluid Metabolomic Profiles of Excess Adiposity and Their Associations With Diabetes Progression Among Puerto Ricans

Introduction: Plasma metabolomic profiles of BMI are associated with type 2 diabetes (T2D) risk but none have examined saliva or combined information from multiple biofluids. Our aim was to identify plasma, saliva, and plasma-saliva multi-fluid metabolomic profiles of BMI and waist circumference (WC) and examine their associations with diabetes progression. Methods: We included 911 participants from the San Juan Overweight Adult Longitudinal Study, a 3-year prospective cohort of overweight Puerto Ricans. At baseline, using LC-MS, we quantified metabolites from saliva (n=635) and plasma (n=1,051). We used elastic net regression with 10-fold cross-validation to identify metabolomic profiles from plasma, saliva, and plasma and saliva (multi-fluid) that were predictive of BMI and WC. We used Cox-proportional hazard models to evaluate associations between metabolomic profiles and diabetes progression adjusting for age, sex, socioeconomic factors, lifestyle, and medication use. Results: For BMI metabolomic profiles, we identified 207 metabolites in plasma, 118 metabolites in saliva, and 225 in the multi-fluid profile. For WC, we identified 157, 89, and 210 metabolites for plasma, saliva, and multi-fluid profiles, respectively. Highly positively weighted metabolites across all BMI and WC metabolomic profiles included those in pathways of alanine and aspartate metabolism, purine metabolism, and sphingomyelins. BMI and WC metabolomic profiles were highly correlated (r=0.80-0.88). Each SD increase in saliva, but not plasma or multi-fluid, metabolic profile of BMI was significantly associated with diabetes progression (Table). Saliva, but not plasma or multi-fluid, metabolomic profile of WC was significantly associated with progression from pre-diabetes to T2D. All associations became stronger after further adjustment for anthropometric measures of BMI and WC. Conclusion: Saliva is an underexplored and easily accessible biofluid to measure metabolites that associate with diabetes progression.