Association of the odd-chain fatty acid content in lipid groups with type 2 diabetes risk

Background: Plasma odd-chain saturated fatty acids (OCFA) are inversely associated with type 2 diabetes (T2D) risk and may serve as biomarkers for dairy fat intake. Their distribution across different lipid classes and consequences for diabetes risk remain unknown. Aim: To investigate the prospective associations of OCFA-containing lipid species with T2D risk and their dietary determinants. Methods: Within the European Prospective Investigation into Cancer and Nutrition-Potsdam study (n = 27,548), we applied a nested case-cohort design (subcohort: n =1,248; T2D cases: n = 820; median follow-up 6.5 years). OCFA-containing lipids included triacylglycerols, free fatty acids (FFA), cholesteryl esters (CE), phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylcholines, lysophospha-tidylethanolamines, monoacylglycerols, and diacylglycerols. We estimated lipid class-specific associa-tions between OCFA-containing lipids and T2D in sex-stratified Cox proportional-hazards models. We investigated correlations between lipids and dietary intakes derived from food-frequency questionnaires. Results: We observed heterogeneous integration of OCFA in different lipid classes: triacylglycerols, FFA, CE, and phosphatidylcholines contributed most to the total OCFA-plasma abundance. The relative con-centration of OCFA was particularly high in monoacylglycerols, and the contribution of C15:0 versus C17:0 to the total OCFA-abundance differed across lipid classes. In women, several OCFA-containing phospholipids were inversely associated with T2D risk [phosphatidylcholine(C15:0), HR Q5 vs Q1: 0.56, 95% CI 0.32-0.97; phosphatidylcholine(C17:0), HR per SD: 0.59, 95% CI 0.48-0.71; lysophospha-tidylcholine(C17:0), HR Q5 vs Q1: 0.42, 95% CI 0.23-0.76]. In men, we did not detect statistically sig-nificant inverse associations in phospholipids, and lysophosphatidylcholine(C15:0) was associated with higher T2D risk (HR Q5 vs. Q1: 1.96, 95% CI 1.06-3.63). Besides, CE(C17:0), monoacylglycerols(C15:0), and diacylglycerols(C15:0) were inversely associated with T2D risk; FFA(C17:0) was positively associated with T2D risk in women. Consumption of fat-rich dairy and fiber-rich foods were positively and red meat inversely correlated to OCFA-containing lipid plasma levels. Conclusions: OCFA-containing lipids are linked to T2D risk in a lipid class and sex-specific manner, and they are correlated with several foods. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).