Ceramides, Particularly Those Containing Very‐Long‐Chain Saturated Fatty Acids, Are Independently Associated With the Triglyceride–Glucose Index in European Individuals With Type 2 Diabetes

AIMS: The triglyceride-glucose (TyG) index is associated with insulin resistance and cardiovascular disease (CVD), but the underlying mechanisms remain unclear. As ceramides are implicated in both insulin resistance and CVD, we investigated the association between the TyG index and plasma ceramides in individuals with Type 2 diabetes (T2D). MATERIALS AND METHODS: We measured total plasma ceramides and seven ceramide species (C16:0, C18:0, C20:0, C22:0, C24:1, C24:0 and C26:0) in 289 European individuals with T2D using liquid chromatography-tandem mass spectrometry. Associations with the TyG index were assessed using univariate and multivariate analyses, including linear regression as the primary analysis. RESULTS: Total ceramides, long-chain saturated fatty acid (LCSFA) ceramides and very-long-chain saturated fatty acid (VLSFA) ceramides were significantly higher in the upper TyG quartiles. The TyG index correlated significantly (p < 0.0001) with total ceramides, LCSFA ceramides, VLSFA ceramides and all ceramide species except C26:0. Multivariable analyses identified total and VLSFA ceramides as independently associated with the TyG index (p < 0.0001). CONCLUSIONS: Our study shows, for the first time, an independent association between the TyG index and plasma ceramides, particularly VLSFA ceramides, in people with T2D. Further research is warranted to elucidate whether this association contributes to the link between the TyG index, insulin resistance and CVD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02045563.