Associations Between the Plasma Lipidome and Metabolic Outcomes in a Population-Based Cohort

Type 2 diabetes (T2D) and metabolic-associated steatotic liver disease (MASLD) are complex metabolic disease states driven by genetic and lifestyle factors, and are major contributors to morbidity and mortality in the United States. Lipid metabolism is heavily implicated in T2D and MASLD, and influenced by lipid-related genes and dietary fat intake. Specifically, the fatty acid desaturase (FADS) gene, has been related to circulating lipids and may influence the impact of dietary fat on plasma lipids. Lipidomic data has allowed further understanding of the lipid-related mechanisms of T2D and MASLD, but few population-based studies of early-middle aged adults have investigated these associations. To address this gap, we used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. We used a targeted panel to investigate the plasma lipidome related to 15-year incident T2D and prevalent MASLD using individual lipid species regression, and multivariate statistics. In addition, we used genetic and diet data to test FADS modification of associations between dietary fat and plasma phospholipids. Our data are distinct from previous population-based cohort studies of lipidomics and T2D and MASLD, as the studied CARDIA participants are generally younger, healthier, and more sociodemographically diverse. The CARDIA Study has been robustly phenotyped including comprehensive diet data, genotyping, computed tomography imaging for MASLD, and prospective diabetes. The younger age and prospective design of CARDIA offers an opportunity to identify markers that occur prior to disease onset, allowing for earlier risk identification.