Metabolome Alterations Linking Sugar Sweetened Beverages with Dyslipidemia in Youth: The Exploring Perinatal Outcomes Among Children Study

OBJECTIVES: To examine the intermediary metabolic alterations associated with sugar sweetened beverage (SSB) intake and cardiometabolic (CM) risk factors in a cohort of diverse youth. METHODS: Data were from 597 participants in the Colorado EPOCH Study who were followed in childhood (∼10 yrs) and adolescence (∼16 yrs). In childhood, SSB intake was assessed by Block Kids Questionnaire and untargeted metabolomics profiling was performed on serum. CM risk factors were assessed across childhood and adolescence by fasting blood draws [glucose, insulin resistance (homeostatic method), lipids]. A “meet in the middle” approach was employed to identify metabolites that mark the relationship between childhood SSB intake and CM risk: In Step 1, we used mixed models to test prospective associations of childhood SSB intake with CM markers across childhood/adolescence. In Step 2, we used least absolute shrinkage and selection operator (LASSO) regression with bootstrapping to identify metabolites associated with childhood SSB intake. Last, we used mixed models to test associations of SSB-associated metabolites (from step 2) with CM markers across childhood/adolescence (from step 1). All analyses were adjust for age, sex, and race/ethnicity. RESULTS: SSB intake in childhood was positively associated with triglycerides across childhood/adolescence [b (95% CI) for 4th vs. 1st SSB quartile: 8.1 (−0.9, 17.0); p-trend = 0.057]. Based on LASSO, 180 metabolites (out of 767) were associated with SSB intake in childhood based on selection in ³40% of bootstrap samples. Among these, 13 metabolites were also associated with triglycerides across childhood/adolescence in the same direction as with SSB intake (Bonferroni-adj. P < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. CONCLUSIONS: In this prospective multi-ethnic cohort, childhood SSB intake was associated with higher triglycerides, which may reflect sugar-induced disruptions in hepatic lipid metabolism. We also identified a panel of lipid metabolites that may serve as intermediary biomarkers linking SSBs to dyslipidemia, offering insights into potential causal mechanisms at play. FUNDING SOURCES: National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK); National Center for Advancing Translational Sciences (NCATS).