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Nutritional Epidemiology (Poster Session)

(P17-082-25) Circulating Bile Acids, Bile Acids Receptor Polymorphisms, and Risk of Chronic Kidney Disease Among Individuals With Newly Diagnosed Type 2 Diabetes: A Prospective Study

Sunday, June 1, 2025
11:45 AM – 12:45 PM ET
Location: Poster Board A-78

    Presenting Author(s)

  • KZ

    Kai Zhu, PhD candidate

    Tongji Medical College, Huazhong University of Science and Technology
    Wuhan, Hubei, China (People's Republic)

    • Co-Author(s)

  • Rui Li, MPH (he/him/his)

    PhD candidate
    Huazhong University of Science and Technology
    Wuhan, Hubei, China (People's Republic)

  • HY

    Hancheng Yu

    Huazhong University of Science and Technology

  • RL

    Ruyi Li, PhD candidate

    None
    Tongji Medical College, Huazhong University of Science and Technology
    wuhan, Hubei, China (People's Republic)

  • LL

    Lin Li, PhD candidate

    Doctoral Student
    Tongji Medical College, Huazhong University of Science and Technology, School of Public Health
    Wuhan, Hubei, China (People's Republic)

  • ZQ

    Zixin Qiu, n/a

    School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Wuhan, Hubei, China (People's Republic)

  • AP

    An Pan, PhD

    Professor
    Huazhong University of Science and Technology
    Wuhan, Hubei, China (People's Republic)

  • GL

    Gang Liu

    Huazhong University of Science and Technology, Tongji Medical College, School of Public Health

Disclosure(s):
Ruyi Li, PhD candidate: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Bile acids (BAs), modulated by diet and gut microbiome, function as ligands for the nuclear farnesoid X receptor (FXR) and may play a role in renal health. To prospectively investigated the associations of circulating BA profiles and their receptor polymorphisms with chronic kidney disease (CKD) in adults with type 2 diabetes (T2D).

Methods: This study included 729 participants with newly diagnosed T2D without prevalent CKD from Dongfeng-Tongji Cohort study in China. Circulating levels of 17 BA subtypes, including primary BAs (PBAs) and secondary BAs (SBAs), were measured.

Results: During 5-years follow-up, 113 incident CKD cases were documented. Higher levels of PBA species and total unconjugated SBAs were significantly associated with a higher risk of incident CKD. The multivariable-adjusted ORs (95% CIs) of CKD comparing the highest to the lowest tertiles were 2.60 (1.50, 4.50) for chenodeoxycholate (CDCA), 3.07 (1.71, 5.54) for glycocholate (GCA), 2.77 (1.58, 4.87) for glycochenodeoxycholate (GCDCA), 2.12 (1.23, 3.63) for taurochenodeoxycholate (TCDCA), 2.66 (1.54, 4.61) for total unconjugated PBAs, 2.49 (1.40, 4.41) for total conjugated PBAs, and 2.24 (1.30, 3.85) for total unconjugated SBAs (all Ptrend < 0.05 and false discovery rate < 0.05). Further, no significant associations were observed for conjugated SBAs. Restricted cubic spline analysis showed a linear relationship between CDCA, GCA, GCDCA, TCDCA, and total unconjugated PBAs, conjugated PBAs, and unconjugated SBAs and incident CKD. In addition, four single-nucleotide polymorphisms (SNPs) in FXR (rs3762108, rs2025801, rs56163822, and rs17030295) were significantly associated with CKD risk in participants with T2D. Significant multiplicative and additive interactions were found between above four SNPs and total unconjugated SBAs on CKD (all Pinteraction < 0.05).

Conclusions: Among adults with newly diagnosed T2D, higher concentrations of circulating PBA, especially CDCA, GCA, GCDCA, and TCDCA, and total unconjugated SBAs was linearly associated with a higher risk of incident CKD. Furthermore, the genetic variations in FXR significantly modified the association of total unconjugated SBAs with CKD.

Funding Sources: The study was funded by the National Natural Science Foundation of China.