Jieli Lu1,2, Shuangyuan Wang1,2, Mian Li1,2, Zhengnan Gao3, Yu Xu4,2, Xinjie Zhao5, Chunyan Hu4,2, Yi Zhang4,2, Ruixin Liu4,2, Ruying Hu6, Lixin Shi7, Ruizhi Zheng4,2, Rui Du4,2, Qing Su8, Jiqiu Wang1,2, Yuhong Chen4,2, Xuefeng Yu9, Li Yan10, Tiange Wang1,2, Zhiyun Zhao4,2, Xiaolin Wang11, Qi Li11, Guijun Qin12, Qin Wan13, Gang Chen14, Min Xu4,2, Meng Dai4,2, Di Zhang4,2, Xulei Tang15, Guixia Wang16, Feixia Shen17, Zuojie Luo18, Yingfen Qin19, Li Chen20, Yanan Huo21, Qiang Li22, Zhen Ye6, Yinfei Zhang23, Chao Liu24, Youmin Wang25, Shengli Wu26, Tao Yang27, Huacong Deng28, Donghui Li29, Shenghan Lai30, Yiming Mu31, Lulu Chen32, Jiajun Zhao33, Guowang Xu5, Guang Ning4,2, Yufang Bi4,2, Weiqing Wang. 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 jielilu@hotmail.com wqingw61@163.com. 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. Dalian Municipal Central Hospital, Dalian, China. 4. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China. 6. Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China. 7. Affiliated Hospital of Guiyang Medical College, Guiyang, China. 8. Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 9. Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 10. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 11. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China jielilu@hotmail.com wqingw61@163.com. 12. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China jielilu@hotmail.com wqingw61@163.com. 13. The Affiliated Hospital of Southwest Medical University, Luzhou, China jielilu@hotmail.com wqingw61@163.com. 14. Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China. 15. The First Hospital of Lanzhou University, Lanzhou, China. 16. The First Hospital of Jilin University, Changchun, China jielilu@hotmail.com wqingw61@163.com. 17. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 18. The First Affiliated Hospital of Guangxi Medical University, Nanning, China. 19. The First Affiliated Hospital of Guangxi Medical University, Nanning, China jielilu@hotmail.com wqingw61@163.com. 20. Qilu Hospital of Shandong University, Jinan, China. 21. Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China. 22. The Second Affiliated Hospital of Harbin Medical University, Harbin, China jielilu@hotmail.com wqingw61@163.com. 23. Central Hospital of Shanghai Jiading District, Shanghai, China. 24. Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing, China. 25. The First Affiliated Hospital of Anhui Medical University, Hefei, China jielilu@hotmail.com wqingw61@163.com. 26. Karamay Municipal People's Hospital, Xinjiang, China. 27. The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 28. The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 29. Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX jielilu@hotmail.com wqingw61@163.com. 30. Johns Hopkins University School of Medicine, Baltimore, MD. 31. Chinese People's Liberation Army General Hospital, Beijing, China. 32. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 33. Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
Abstract
OBJECTIVE: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.
OBJECTIVE: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.
Authors: S Ciardullo; F Zerbini; S Perra; E Muraca; R Cannistraci; M Lauriola; P Grosso; G Lattuada; G Ippoliti; A Mortara; G Manzoni; G Perseghin Journal: J Endocrinol Invest Date: 2020-08-10 Impact factor: 4.256
Authors: Cong Xie; Weikun Huang; Richard L Young; Karen L Jones; Michael Horowitz; Christopher K Rayner; Tongzhi Wu Journal: Nutrients Date: 2021-03-28 Impact factor: 5.717