%0 Journal Article
%T Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.
%A Wang S
%A Hu C
%A Lin H
%A Jia X
%A Hu R
%A Zheng R
%A Li M
%A Xu Y
%A Xu M
%A Zheng J
%A Zhao X
%A Li Y
%A Chen L
%A Zeng T
%A Ye Z
%A Shi L
%A Su Q
%A Chen Y
%A Yu X
%A Yan L
%A Wang T
%A Zhao Z
%A Qin G
%A Wan Q
%A Chen G
%A Dai M
%A Zhang D
%A Qiu B
%A Zhu X
%A Liu R
%A Wang X
%A Tang X
%A Gao Z
%A Shen F
%A Gu X
%A Luo Z
%A Qin Y
%A Chen L
%A Hou X
%A Huo Y
%A Li Q
%A Wang G
%A Zhang Y
%A Liu C
%A Wang Y
%A Wu S
%A Yang T
%A Deng H
%A Zhao J
%A Mu Y
%A Xu G
%A Lai S
%A Li D
%A Ning G
%A Wang W
%A Bi Y
%A Lu J
%A  
%J Am J Clin Nutr
%V 120
%N 2
%D 2024 Aug 8
%M 38729573
%F 8.472
%R 10.1016/j.ajcnut.2024.05.003
%X <B>BACKGROUND: </B>Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking.<BR><B>OBJECTIVE: </B>Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults.<BR><B>METHODS: </B>This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes.<BR><B>RESULTS: </B>The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset.<BR><B>CONCLUSIONS: </B>These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.