Clusters of fatty acids in the serum triacylglyceride fraction associate with the disorders of type 2 diabetes

Aims: Our aim was to examine longitudinal associations of triacylglyceride fatty acid (TGFA) composition with insulin sensitivity (IS) and beta-cell function. Methods: Adults at-risk for T2D (n=477) had glucose and insulin measured from a glucose challenge at 3 time points over 6 years. The outcome variables Matsuda index (ISI), HOMA2-%S, Insulinogenic Index over HOMA-IR (IGI/IR), and Insulin Secretion-Sensitivity Index-2 (ISSI-2) were computed from the glucose challenge. Gas chromatography quantified TGFA composition from the baseline. We used adjusted generalized estimating equations (GEE) models and partial least squares (PLS) regression for the analysis. Results: In adjusted GEE models, four TGFA (14:0, 16:0, 14:1n-7, 16:1n-7 as mol%) had strong negative associations with IS while others (e.g. 18:1n-7, 18:1n-9, 20:2n-6, 20:5n-3) had strong positive associations. Few associations were seen for beta-cell function, except for 16:0 and 18:1n-7. PLS analysis indicated four TGFA (14:0, 16:0, 14:1n-7, 16:1n-7) that clustered together and strongly related with lower IS. These four TGFA also correlated highly (r>0.4) with clinically measured TG. Conclusions: We found that higher proportions of a cluster of four TGFA strongly related with lower IS as well as hypertriglyceridemia. Previous research suggests these four FA are also strongly influenced by de novo lipogenesis, particularly from carbohydrates.