TY - JOUR
T1 - Association of Serum Bile Acids Profile and Pathway Dysregulation With the Risk of Developing Diabetes Among Normoglycemic Chinese Adults
T2 - Findings From the 4C Study
AU - 4C Study Group
AU - Lu, Jieli
AU - Wang, Shuangyuan
AU - Li, Mian
AU - Gao, Zhengnan
AU - Xu, Yu
AU - Zhao, Xinjie
AU - Hu, Chunyan
AU - Zhang, Yi
AU - Liu, Ruixin
AU - Hu, Ruying
AU - Shi, Lixin
AU - Zheng, Ruizhi
AU - Du, Rui
AU - Su, Qing
AU - Wang, Jiqiu
AU - Chen, Yuhong
AU - Yu, Xuefeng
AU - Yan, Li
AU - Wang, Tiange
AU - Zhao, Zhiyun
AU - Wang, Xiaolin
AU - Li, Qi
AU - Qin, Guijun
AU - Wan, Qin
AU - Chen, Gang
AU - Xu, Min
AU - Dai, Meng
AU - Zhang, Di
AU - Tang, Xulei
AU - Wang, Guixia
AU - Shen, Feixia
AU - Luo, Zuojie
AU - Qin, Yingfen
AU - Chen, Li
AU - Huo, Yanan
AU - Li, Qiang
AU - Ye, Zhen
AU - Zhang, Yinfei
AU - Liu, Chao
AU - Wang, Youmin
AU - Wu, Shengli
AU - Yang, Tao
AU - Deng, Huacong
AU - Li, Donghui
AU - Lai, Shenghan
AU - Mu, Yiming
AU - Chen, Lulu
AU - Zhao, Jiajun
AU - Xu, Guowang
AU - Ning, Guang
N1 - Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
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U2 - 10.2337/dc20-0884
DO - 10.2337/dc20-0884
M3 - Article
C2 - 33355246
AN - SCOPUS:85100280823
SN - 1935-5548
VL - 44
SP - 499
EP - 510
JO - Diabetes care
JF - Diabetes care
IS - 2
ER -