Circulating short-chain and branched short-chain fatty acids and the risk of incident type 2 diabetes: findings from the 4C study

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) (<i>P</i> < 0.05). Interestingly, gender-specific analysis showed that per standard deviation (SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio (95% confidence interval) of 1.16 (1.05-1.29) for total SCFAs and 1.18 (1.07-1.31) for propionate, respectively (<i>P</i> < 0.05, false discovery rate (FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate (<i>P</i> <sub>interaction</sub> < 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant (<i>P</i> < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.

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Journal
Life Metabolism
Published
2025-01-22
DOI
https://doi.org/10.1093/lifemeta/loaf001
Citations
3
Primary Topic
Fatty Acid Research and Health
Type
article
Field-Weighted Citation Impact
3.36

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article

Circulating short-chain and branched short-chain fatty acids and the risk of incident type 2 diabetes: findings from the 4C study

Meng Dai, Jiajun Zhao, Yiming Mu, Jieli Lu et al.
3 citations
Life Metabolism
Fatty Acid Research and Health
3.36
article

Circulating short-chain and branched short-chain fatty acids and the risk of incident type 2 diabetes: findings from the 4C study

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

Abstract

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) (<i>P</i> < 0.05). Interestingly, gender-specific analysis showed that per standard deviation (SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio (95% confidence interval) of 1.16 (1.05-1.29) for total SCFAs and 1.18 (1.07-1.31) for propionate, respectively (<i>P</i> < 0.05, false discovery rate (FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate (<i>P</i> <sub>interaction</sub> < 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant (<i>P</i> < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.

Life MetabolismVol. 4(2)
Guiyang College of Traditional Chinese Medicine (CN), University of Maryland, Baltimore (US), Fujian Medical University (CN), Union Hospital (HK), The University of Texas MD Anderson Cancer Center (US), Nanchang University (CN), Guiyang Medical University (CN), Shandong University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Guangxi Medical University (CN), Dalian Institute of Chemical Physics (CN), Shanghai Jiao Tong University (CN), Jilin University (CN), Anhui Medical University (CN), Chinese Academy of Sciences (CN), Wenzhou Medical University (CN), XinHua Hospital (CN), Ruijin Hospital (CN), First Affiliated Hospital of Wenzhou Medical University (CN), Chinese General Hospital College of Nursing and Liberal Arts (PH), Affiliated Hospital of Southwest Medical University (CN), Jiading District Central Hospital (CN), Sun Yat-sen Memorial Hospital (CN), People's Liberation Army No. 150 Hospital (CN), Dalian Municipal Central Hospital (CN), Jiangxi Provincial People's Hospital (CN), Affiliated Hospital of Guizhou Medical University (CN), Shandong Provincial Hospital (CN), First Hospital of Jilin University (CN), First Affiliated Hospital of GuangXi Medical University (CN), Wuhan Union Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Second Affiliated Hospital of Harbin Medical University (CN), Nanyang Medical College (CN), Zhejiang Center for Disease Control and Prevention (CN), First Affiliated Hospital of Anhui Medical University (CN), Fujian Provincial Hospital (CN), Karamay Central Hospital (CN), Jiangsu Province Hospital (CN), First Affiliated Hospital of Zhengzhou University (CN), Tongji Hospital (CN), Chinese People's Liberation Army (CN), Qilu Hospital of Shandong University (CN), First Hospital of Lanzhou University (CN), Union Hospital (CN), Huazhong University of Science and Technology (CN), Lanzhou University (CN), Nanjing Medical University (CN), Chongqing Medical University (CN)
Shanghai Municipal Health Commission, National Natural Science Foundation of China, Shanghai Rising-Star Program, National Science and Technology Major Project
Good health and well-being
Openalex Percentile: Top 10%
Fatty Acid Research and Health
3.36
DOIOpen Access PDFOpenAlex
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