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

Our aim was to examine longitudinal associations of triacylglyceride fatty acid (TGFA) composition with insulin sensitivity (IS) and β-cell function. Adults at risk for T2D (n = 477) had glucose and insulin measured from a glucose challenge at three time points over 6 years. The outcome variables Matsuda insulin sensitivity index, homeostatic model of assessment 2-percent sensitivity (HOMA2-%S), Insulinogenic Index over HOMA-IR (IGI/IR), and Insulin Secretion-Sensitivity Index-2 were computed from the glucose challenge. Gas chromatography quantified TGFA composition from the baseline. We used adjusted generalized estimating equation (GEE) models and partial least squares (PLS) regression for the analysis. In adjusted GEE models, four TGFAs (14:0, 16:0, 14:1n-7, and 16:1n-7 as mol%) had strong negative associations with IS, whereas others (e.g., 18:1n-7, 18:1n-9, 20:2n-6, and 20:5n-3) had strong positive associations. Few associations were seen for β-cell function, except for 16:0, 18:1n-7, and 20:2n-6. PLS analysis indicated four TGFAs (14:0, 16:0, 14:1n-7, and 16:1n-7) that clustered together and strongly related with lower IS. These four TGFAs also correlated highly (r > 0.4) with clinically measured triacylglyceride. We found that higher proportions of a cluster of four TGFAs strongly related with lower IS as well as hypertriglyceridemia, suggesting that only a few FAs within the TGFA composition may primarily explain lipids' role in glucose dysregulation.