{Reference Type}: Journal Article
{Title}: Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.
{Author}: Wang S;Hu C;Lin H;Jia X;Hu R;Zheng R;Li M;Xu Y;Xu M;Zheng J;Zhao X;Li Y;Chen L;Zeng T;Ye Z;Shi L;Su Q;Chen Y;Yu X;Yan L;Wang T;Zhao Z;Qin G;Wan Q;Chen G;Dai M;Zhang D;Qiu B;Zhu X;Liu R;Wang X;Tang X;Gao Z;Shen F;Gu X;Luo Z;Qin Y;Chen L;Hou X;Huo Y;Li Q;Wang G;Zhang Y;Liu C;Wang Y;Wu S;Yang T;Deng H;Zhao J;Mu Y;Xu G;Lai S;Li D;Ning G;Wang W;Bi Y;Lu J; ;
{Journal}: Am J Clin Nutr
{Volume}: 120
{Issue}: 2
{Year}: 2024 Aug 8
{Factor}: 8.472
{DOI}: 10.1016/j.ajcnut.2024.05.003
{Abstract}: <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.