ArticleCell reports. Medicine2022
Amino acids, microbiota-related metabolites, and the risk of incident diabetes among normoglycemic Chinese adults: Findings from the 4C study.
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Who cites it
43 citing papers in PubMed, 61 citations in OpenAlex.
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- CBP/p300 is critical for the expansion and maintenance of functional pancreatic α cell mass.Nature communications · 2026Article
- Ancestry-specific genetics of amino acids and microbiota-related metabolites reveal causal effects on cardiometabolic disease in Chinese populations.Cardiovascular diabetology · 2026Article
- O-Acetyl-Serine Supplementation Enhances Insulin Secretion and Improves Postprandial Glycaemia in Lean and Prediabetic Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Identifying the Ratio of Circulating Cinnamoylglycine to Isoleucine as a Biomarker Linking Diet Quality, Microbial Metabolism, and Type 2 Diabetes Risk in the Coronary Artery Risk Development in Young Adults (CARDIA) Cohorts.The Journal of nutrition · 2026Article
- The Association Between Amino Acids and the Onset and Progression of Type 2 Diabetes Mellitus: A Comprehensive Analysis Based on UK Biobank Database.Journal of diabetes research · 2026Article
- A plasma N-acetyl amino acid panel for type 2 diabetes discrimination built by targeted LC-MS/MS: A case-control study.Frontiers in medicine · 2026Article
- Phenotyping obesity through a two-dimensional tree structure reveals cardiometabolic heterogeneity.Cell reports. Medicine · 2025Article
- Hepatic CBP/p300 Orchestrate Amino Acid-Driven Gluconeogenesis through Histone Crotonylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Emerging Insights into the Relationship Between Amino Acid Metabolism and Diabetic Cardiomyopathy.Biomolecules · 2025Review
- Bile Acids and Type 2 Diabetes: Roles in Glucose Homeostasis and Therapeutic Opportunities.Metabolites · 2025Review
- Gut Microbiota Dysbiosis and Its Impact on Type 2 Diabetes: From Pathogenesis to Therapeutic Strategies.Metabolites · 2025Review
- Metabolomics in cardiometabolic diseases: Key biomarkers and therapeutic implications for insulin resistance and diabetes.Journal of internal medicine · 2025Review
- Circulating short-chain and branched short-chain fatty acids and the risk of incident type 2 diabetes: findings from the 4C study.Life metabolism · 2025Article
- Sugar-sweetened beverage intake, gut microbiota, circulating metabolites, and diabetes risk in Hispanic Community Health Study/Study of Latinos.Cell metabolism · 2025Article
- Proline exacerbates hepatic gluconeogenesis via paraspeckle-dependent mRNA retention.Nature metabolism · 2025Article
- Accelerated biological aging, mediating amino acids, and risk of incident type 2 diabetes: a prospective cohort study.Journal of endocrinological investigation · 2025Article
- Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings From the 4C Study.The Journal of clinical endocrinology and metabolism · 2025Article
- Metabolite 2-aminoadipic acid: implications for metabolic disorders and therapeutic opportunities.Frontiers in pharmacology · 2025Review
- Dysbiosis and Regulation of Gut Microbiota in Type 2 Diabetes Mellitus.Current pharmaceutical biotechnology · 2025Review
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Authors and funding
54 authors at 20 institutions in 2 countries.
Shuangyuan WangDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Mian LiDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Hong LinDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Guixia WangThe First Hospital of Jilin University, Changchun, China.
Yu XuDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Xinjie ZhaoKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Chunyan HuDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Yi ZhangDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Ruizhi ZhengDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Ruying HuZhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
Lixin ShiAffiliated Hospital of Guiyang Medical College, Guiyang, China.
Rui DuDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Qing SuXinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Jiqiu WangDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Yuhong ChenDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Xuefeng YuTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li YanSun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Tiange WangDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Zhiyun ZhaoDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Ruixin LiuDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Xiaolin WangKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Qi LiKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Guijun QinThe First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Qin WanThe Affiliated Hospital of Southwest Medical University, Luzhou, China.
Gang ChenFujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
Min XuDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Meng DaiDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Di ZhangDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China.
Xulei TangThe First Hospital of Lanzhou University, Lanzhou, China.
Zhengnan GaoDalian Municipal Central Hospital, Dalian, China.
Feixia ShenThe First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Zuojie LuoThe First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Yingfen QinThe First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Li ChenQilu Hospital of Shandong University, Jinan, China.
Yanan HuoJiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China.
Qiang LiThe Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Zhen YeZhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China.
Yinfei ZhangCentral Hospital of Shanghai Jiading District, Shanghai, China.
Chao LiuJiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China.
Youmin WangThe First Affiliated Hospital of Anhui Medical University, Hefei, China.
Shengli WuKaramay Municipal People's Hospital, Xinjiang, China.
Tao YangThe First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Huacong DengThe First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jiajun ZhaoShandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Shenghan LaiJohns Hopkins University School of Medicine, Baltimore, MD, USA.
Yiming MuChinese People's Liberation Army General Hospital, Beijing, China.
Lulu ChenUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Donghui LiDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Guowang XuKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
Guang NingDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China. Electronic address: gning@sibs.ac.cn.
Weiqing WangDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China. Electronic address: wqingw61@163.com.
Yufang BiDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China. Electronic address: byf10784@rjh.com.cn.
Jieli LuDepartment 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, 197 Ruijin 2nd Rd, Shanghai 200025, China. Electronic address: jielilu@hotmail.com.
4C Study Group
Shanghai Jiao Tong University · CNRuijin Hospital · CNChinese Academy of Sciences · CNDalian Institute of Chemical Physics · CNFirst Affiliated Hospital of GuangXi Medical University · CNJiading District Central Hospital · CNJiangsu Province Hospital · CNWuhan Union Hospital · CNZhejiang Center for Disease Control and Prevention · CNAffiliated Hospital of Southwest Medical University · CNChinese People's Liberation Army · CNChongqing Medical University · CNDalian Municipal Central Hospital · CNFirst Affiliated Hospital of Anhui Medical University · CNFirst Affiliated Hospital of Wenzhou Medical University · CNFirst Affiliated Hospital of Zhengzhou University · CNFujian Provincial Hospital · CNHarbin Medical University · CNJilin University · CNJohns Hopkins University · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor-metabolite-diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.
Indexed as
Diabetes Mellitus, Type 2Microbiota2-Aminoadipic AcidAdultAlanineAmino AcidsAsparagineGlutamic AcidHistidineHomoserineHumansLipidsMethionineProlineUric Acid2-Aminoadipic AcidAlanineAmino AcidsAsparagineGlutamic AcidHistidineHomoserineLipidsMethionineProlineUric Acidamino aciddiabetesmediationmicrobiota-related metabolitesrisk factor
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