Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status

Background: Bile acids (BAs) have been demonstrated to exert a variety of metabolic effects and alterations in BAs have been reported in patients with obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, it is unclear which metabolic condition is the main contributor to alterations in BAs. In this study, we investigate the associations between different BA profiles with glycemia, obesity or IR status. Methods: Fasting serum concentrations of 15 BA species were determined in a total of 241 individuals (71 drug-naive patients with T2DM, 95 patients with impaired fasting glucose [IFG], and 75 healthy controls. Results: A comparison of the mean values of the BAs revealed no significant differences between normoglycemic controls and patients with IFG or T2DM. However, when the entire cohort was divided according to the presence of IR as determined by a homeostasis model assessment of insulin resistance (HOMA-IR) value >2.5, the levels of total BA and most species of BAs were significantly higher in patients with IR than in patients without. In the correlation analysis, most species of BAs, as well as total BA, were significantly associated with HOMA-IR levels. Furthermore, when the subjects were divided into four groups according to IR and diabetic status, subjects with IR had significantly higher total BAs than participants without IR both in diabetic and non-diabetic groups. Ultimately, multiple linear regression analysis identified HOMA-IR as the only significant contributor to most serum BA species. Conclusions: Our findings support the essential role of IR in regulating BA metabolism and that this effect is independent of diabetic status.