Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study

Xiaojing Jia; Hong Lin; Yilan Ding; Xuejiang Gu; Shuangyuan Wang; Yu Xu; Min Xu; Xinjie Zhao; Lulu Chen; Tianshu Zeng; Lixin Shi; Qing Su; Yuhong Chen; Xuefeng Yu; Li Yan; Guijun Qin; Qin Wan; Gang Chen; Xulei Tang; Zhengnan Gao; Feixia Shen; Ruying Hu; 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; Guang Ning; Weiqing Wang; Yufang Bi; Jieli Lu

doi:10.1210/clinem/dgae483

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study

J Clin Endocrinol Metab. 2024 Jul 20:dgae483. doi: 10.1210/clinem/dgae483. Online ahead of print.

Authors

Xiaojing Jia^{1

2}, Hong Lin^{1

2}, Yilan Ding^{1

2}, Xuejiang Gu³, Shuangyuan Wang^{1

2}, Yu Xu^{1

2}, Min Xu^{1

2}, Xinjie Zhao⁴, Lulu Chen⁵, Tianshu Zeng⁵, Lixin Shi⁶, Qing Su⁷, Yuhong Chen^{1

2}, Xuefeng Yu⁸, Li Yan⁹, Guijun Qin¹⁰, Qin Wan¹¹, Gang Chen¹², Xulei Tang¹³, Zhengnan Gao¹⁴, Feixia Shen³, Ruying Hu¹⁵, Zuojie Luo¹⁶, Yingfen Qin¹⁶, Li Chen¹⁷, Xinguo Hou¹⁷, Yanan Huo¹⁸, Qiang Li¹⁹, Guixia Wang²⁰, Yinfei Zhang²¹, Chao Liu²², Youmin Wang²³, Shengli Wu²⁴, Tao Yang²⁵, Huacong Deng²⁶, Jiajun Zhao²⁷, Yiming Mu²⁸, Guang Ning^{1

2}, Weiqing Wang^{1

2}, Yufang Bi^{1

2}, Jieli Lu^{1

2}

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.
² 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.
³ The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
⁵ Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Affiliated Hospital of Guiyang Medical College, Guiyang, China.
⁷ Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁸ Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁹ Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
¹⁰ The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
¹¹ The Affiliated Hospital of Southwest Medical University, Luzhou, China.
¹² Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
¹³ The First Hospital of Lanzhou University, Lanzhou, China.
¹⁴ Dalian Municipal Central Hospital, Dalian, China.
¹⁵ Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
¹⁶ The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
¹⁷ Qilu Hospital of Shandong University, Jinan, China.
¹⁸ Jiangxi provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.
¹⁹ The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
²⁰ The First Hospital of Jilin University, Changchun, China.
²¹ Central Hospital of Shanghai Jiading District, Shanghai, China.
²² Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China.
²³ The First Affiliated Hospital of Anhui Medical University, Hefei, China.
²⁴ Karamay Municipal People's Hospital, Xinjiang, China.
²⁵ The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
²⁶ The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
²⁷ Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
²⁸ Chinese People's Liberation Army General Hospital, Beijing, China.

PMID: 39031583
DOI: 10.1210/clinem/dgae483

Abstract

Context: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies.

Objective: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk.

Methods: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants.

Results: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003).

Conclusions: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Keywords: genetic risk; lifestyle; medium-chain fatty acids; prospective; type 2 diabetes.