Association of Circulating Long-Chain Free Fatty Acids and Incident Diabetes Risk Among Normoglycemic Chinese Adults: A Prospective Nested Case-Control Study

Shuangyuan Wang; Chunyan Hu; Hong Lin; Xiaojing Jia; Ruying Hu; Ruizhi Zheng; Mian Li; Yu Xu; Min Xu; Jie Zheng; Xinjie Zhao; Yanli Li; Lulu Chen; Tianshu Zeng; Zhen Ye; Lixin Shi; Qing Su; Yuhong Chen; Xuefeng Yu; Li Yan; Tiange Wang; Zhiyun Zhao; Guijun Qin; Qin Wan; Gang Chen; Meng Dai; Di Zhang; Bihan Qiu; Xiaoyan Zhu; Ruixin Liu; Xiao Wang; Xulei Tang; Zhengnan Gao; Feixia Shen; Xuejiang Gu; Zuojie Luo; Yingfen Qin; Li Chen; Xinguo Hou; Yanan Huo; Qiang Li; Guixia Wang; Yinfei Zhang; Chao Liu; Youmin Wang; Shengli Wu; Tao Yang; Huacong Deng; Jiajun Zhao; Yiming Mu; Guowang Xu; Shenghan Lai; Donghui Li; Guang Ning; Weiqing Wang; Yufang Bi; Jieli Lu; 4C Study Group

doi:10.1016/j.ajcnut.2024.05.003

Association of Circulating Long-Chain Free Fatty Acids and Incident Diabetes Risk Among Normoglycemic Chinese Adults: A Prospective Nested Case-Control Study

Am J Clin Nutr. 2024 May 8:S0002-9165(24)00465-9. doi: 10.1016/j.ajcnut.2024.05.003. Online ahead of print.

Authors

Shuangyuan Wang¹, Chunyan Hu¹, Hong Lin¹, Xiaojing Jia¹, Ruying Hu², Ruizhi Zheng¹, Mian Li¹, Yu Xu¹, Min Xu¹, Jie Zheng¹, Xinjie Zhao³, Yanli Li³, Lulu Chen⁴, Tianshu Zeng⁴, Zhen Ye², Lixin Shi⁵, Qing Su⁶, Yuhong Chen¹, Xuefeng Yu⁷, Li Yan⁸, Tiange Wang¹, Zhiyun Zhao¹, Guijun Qin⁹, Qin Wan¹⁰, Gang Chen¹¹, Meng Dai¹, Di Zhang¹, Bihan Qiu¹, Xiaoyan Zhu¹, Ruixin Liu¹, Xiao Wang¹, Xulei Tang¹², Zhengnan Gao¹³, Feixia Shen¹⁴, Xuejiang Gu¹⁴, Zuojie Luo¹⁵, Yingfen Qin¹⁵, Li Chen¹⁶, Xinguo Hou¹⁶, Yanan Huo¹⁷, Qiang Li¹⁸, Guixia Wang¹⁹, Yinfei Zhang²⁰, Chao Liu²¹, Youmin Wang²², Shengli Wu²³, Tao Yang²⁴, Huacong Deng²⁵, Jiajun Zhao²⁶, Yiming Mu²⁷, Guowang Xu³, Shenghan Lai²⁸, Donghui Li²⁹, Guang Ning¹, Weiqing Wang³⁰, Yufang Bi³¹, Jieli Lu³²; 4C Study Group

Affiliations

¹ Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;; Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
² Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
³ Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
⁴ Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Affiliated Hospital of Guiyang Medical College, Guiyang, China.
⁶ Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁷ Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁸ Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
⁹ The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹⁰ The Affiliated Hospital of Southwest Medical University, Luzhou, China.
¹¹ Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
¹² The First Hospital of Lanzhou University, Lanzhou, China.
¹³ Dalian Municipal Central Hospital, Dalian, China.
¹⁴ The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹⁵ The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
¹⁶ Qilu Hospital of Shandong University, Jinan, China.
¹⁷ Jiangxi provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.
¹⁸ The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
¹⁹ The First Hospital of Jilin University, Changchun, China.
²⁰ Central Hospital of Shanghai Jiading District, Shanghai, China.
²¹ Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China.
²² The First Affiliated Hospital of Anhui Medical University, Hefei, China.
²³ Karamay Municipal People's Hospital, Xinjiang, China.
²⁴ The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
²⁵ The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
²⁶ Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
²⁷ Chinese People's Liberation Army General Hospital, Beijing, China.
²⁸ Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
²⁹ Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³⁰ Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;; Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China;. Electronic address: wqingw61@163.com.
³¹ Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;; Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China;. Electronic address: byf10784@rjh.com.cn.
³² Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;; Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China;. Electronic address: jielilu@hotmail.com.

PMID: 38729573
DOI: 10.1016/j.ajcnut.2024.05.003

Abstract

Background: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, comprehensive assessment of the associations in normoglycemic populations is lacking.

Objective: Our study aims to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults.

Methods: 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 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.

Results: 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 to 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[95%CI]: 0.85[0.76-0.94]), PUFAs 20:4 (0.84[0.75-0.94]) and 24:2 (0.87[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 [0.61-0.99] (P= 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset.

Conclusions: 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.

Keywords: Free fatty acids; Long-chain fatty acids; Normoglycemic population; Prospective; diabetes.