Associations of Lipid Metabolites with Insulin Resistance and Hypertriglyceridemia in Youth

This study is aimed at exploring the associations of lipid metabolites with insulin resistance (IR) and hypertriglyceridemia among children and adolescents. We recruited 630 young individuals aged 4 to 17 years and divided them into two groups: low-IR and high-IR. MS metabolomic analysis was used to measure 75 lipid metabolites in plasma. IR-specific lipid metabolites are illustrated via volcano plot. We used regression models to evaluate the relationships between IR-specific lipid metabolites and IR and hypertriglyceridemia. Furthermore, we applied bootstrapping to test the mediating effect of triglyceride (TG) on the relationship between IR-specific lipid metabolites and IR. In our study, there were 379 individuals in the low-IR group and 251 individuals in the high-IR group. We identified 9 children-specific IR-associated lipid metabolites, of which 16:0-18:1 PE, 18:0-18:2 PE, and 18:0 PE were positively associated with the risk of IR (OR = 1.909, 95% CI = 1.084-3.361, p = 0.025; OR = 1.890, 95% CI = 1.065-3.355, p = 0.030; respectively). Additionally, correlation heat maps revealed associations between TG and 16:0-18:1 PE, 26:0 Lyso PC, and 22:1 (Cis) PC. Further multivariate binary logistics regression analysis revealed that 16:0-18:1 PE was significantly associated with hypertriglyceridemia (OR = 1.949, 95% CI = 1.212-3.133, p = 0.006). TG plays a partial mediating role in the relationship between 16:0-18:1 PE and HOMA-IR, with the proportion of the mediation effect relative to the total effect being 18.29% (95% CI of the mediating effect for TG was 0.004-0.082). Increased levels of 16:0-18:1 PE, 18:0-18:2 PE, and 18:0 PE are associated with increased risks of IR. Increased levels of 16:0-18:1 PE are associated with increased risks of hypertriglyceridemia. TG may mediate the impact of IR driven by 16:0-18:1 PE.