Association of Serum Bile Acids Profile and Pathway Dysregulation With the Risk of Developing Diabetes Among Normoglycemic Chinese Adults: Findings From the 4C Study.

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.

• Authors: Jieli Lu, Shuangyuan Wang, Mian Li, Zhengnan Gao, Yu Xu, Xinjie Zhao, Chunyan Hu, Yi Zhang, Ruixin Liu, Ruying Hu, Lixin Shi, Ruizhi Zheng, Rui Du, Qing Su, Jiqiu Wang, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Xiaolin Wang, Qi Li, Guijun Qin, Qin Wan, Gang Chen, Min Xu, Meng Dai, Di Zhang, Xulei Tang, Guixia Wang, Feixia Shen, Zuojie Luo, Yingfen Qin, Li Chen, Yanan Huo, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Donghui Li, Shenghan Lai, Yiming Mu, Lulu Chen, Jiajun Zhao, Guowang Xu, Guang Ning, Yufang Bi, Weiqing Wang, 4C Study Group
• Journal: Diabetes care (Diabetes Care) Vol. 44 Issue 2 Pg. 499-510 (02 2021) ISSN: 1935-5548 [Electronic] United States
• PMID: 33355246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Diabetes Association.

Chemical References

• Bile Acids and Salts

Topics

• Adult
• Bile Acids and Salts
• China (epidemiology)
• Diabetes Mellitus, Type 2 (epidemiology)
• Fasting
• Humans
• Insulin Resistance
• Middle Aged