Bile acid diarrhea is associated with an increased risk of type 2 diabetes and cardiovascular disease: a nationwide cohort study.

Introduction: Bile acid diarrhea (BAD) is a socially debilitating disease characterized by diarrhea, fecal urgency, and fecal incontinence. It is caused by excessive amounts of bile acids in the colon and is estimated to affect up to 1% of the population. Among other actions, bile acids regulate systemic glucose and lipid metabolism, and BAD has been associated with a dysmetabolic prediabetic-like state. Here, we investigate the association between BAD and type 2 diabetes (T2D) and cardiovascular disease (CVD), respectively.

Methods: By using nationwide Danish health registries, individuals with BAD were identified by referral to the diagnostic 75selenium-homotaurocholic acid test followed by redemption of a prescription of a bile acid sequestrant within 365 days or a BAD diagnosis code (n=5,954). A reference population of age and sex-matched individuals was included for comparison (n=59,540).

Results: More individuals with BAD than controls developed T2D (8.8% vs. 5.2%) and experienced CVD (22.7% vs. 18.0%) after index date (i.e., BAD diagnosis or matching, respectively). Sensitivity analyses revealed earlier onset of T2D and CVD in the BAD population compared with matches but no difference between sexes. The cause-specific hazards for T2D and CVD were 1.79 and 1.34, respectively, in the BAD population compared with matches. All-cause mortality-but not CVD-related mortality-was increased among individuals with BAD compared with matches.

Discussion: BAD is associated with increased risk and earlier onset of T2D and CVD, respectively, as well as disturbed glucose and lipid metabolism, indicating BAD as a high-risk condition requiring intensified monitoring and relevant preventive interventions.