(P19-029-23) Gut Microbiota-Derived Secondary Bile Acids, Bile Acids Receptor Polymorphisms, and Risk of Cardiovascular Disease in Individuals With Newly Diagnosed Type 2 Diabetes

Objectives: Secondary bile acids (SBAs), the products of bacterial metabolism, have been implicated in cardiovascular health. Dietary component can modulate gut microbiota composition and bile acid metabolism. We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).

Methods: Circulating SBAs and their conjugated forms were quantified using LC-MS/MS in 1234 participants with newly diagnosed T2D from the Dongfeng-Tongji cohort, China. Fifteen single nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for the associations between SBAs and CVD risk.

Results: During a median follow-up of 5.7 years, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs (sum of deoxycholic acid [DCA], lithocholic acid, and ursodeoxycholic acid) and DCA were significantly associated with a higher risk of CVD among people with T2D, with an HR (95% CI) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per SD increment in natural log-transformed unconjugated SBAs and DCA was associated with 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) increased risk of CVD, respectively. In addition, genetic variants in bile acid receptor encoding gene (rs56163822 TT vs GG and rs17030295 TT vs CC) were significantly associated with a 121-129% higher risk of CVD among individuals with T2D.

Conclusions: Higher level of unconjugated SBAs, especially DCA, was linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support a potential role of gut microbiota-derived SBAs on cardiovascular health in individuals with T2D.

Funding Sources: GL is supported by grant from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars.