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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 associations between glycerolipids and T2D. Objective We aimed to assess associations between plasma glycerolipids and incident T2D and to explore a potential role of liver fat accumulation in the associations. Methods This was a prospective cohort study with 6 years of follow-up. The study population included 1781 Chinese participants aged 50 to 70 years. The main outcome measure was incident T2D. Results At the 6-year resurvey, 463 participants had 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% CIs) ranging from 1.16 (1.05-1.27) to 1.23 (1.11-1.36) per SD increment of glycerolipids. However, additional adjustment for fatty liver index largely attenuated these findings (RR [95% CI] 0.88 [0.81 to 0.95] to 1.10 [1.01 to 1.21]). Mediation analyses suggested that the fatty liver index explained 12% to 28% of the glycerolipids-T2D associations (all P &amp;lt; 0.01). Conclusion 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.

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