Circulating Glycerolipids, Fatty Liver Index and Incidence of Type 2 Diabetes: A Prospective Study among Chinese.

CONTEXT Few lipidomic studies have specifically investigated the association of circulating glycerolipids and type 2 diabetes (T2D) risk, especially among Asian populations. It remains unknown whether or to what degree fatty liver could explain the glycerolipids-T2D associations. OBJECTIVE We aimed to assess associations between plasma glycerolipids and incident T2D, and explore a potential role of liver fat accumulation in the associations. DESIGN A prospective cohort study with 6-year of follow-up. PARTICIPANTS This work included 1,781 Chinese aged 50-70 years. MAIN OUTCOME MEASURES T2D. RESULTS At 6-year resurvey, 463 participants developed T2D. At the false-discovery rate (FDR) of 5%, 43 of 104 glycerolipids were significantly associated with incident T2D risk after multivariate adjustment for conventional risk factors. After further controlling for glycated hemoglobin (HbA1c), 9 of the 43 glycerolipids remained significant, including 2 diacylglycerols (DAGs)(16:1/20:4, 18:2/20:5) and 7 triacylglycerols (TAGs)(46:1, 48:0, 48:1, 50:0, 50:1, 50:2, and 52:2), with relative risks (RRs) (95% confidence intervals [CIs]) ranging from 1.16 (1.05 to 1.27) to 1.23 (1.11 to 1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index (FLI) largely attenuated these findings (RRs [95% CIs] were 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the FLI explained 12%-28% glycerolipids-T2D associations (all p < 0.01). CONCLUSIONS Higher plasma levels of DAGs and TAGs were associated with increased incident T2D risk in this Chinese population, which might be partially explained by liver fat accumulation.