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 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 < 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.