Abstract
A paucity of information currently exists on plasma bile acid (BA) profiles in patients with and without type 2 diabetes mellitus (T2DM). We assayed 14 plasma BA species in 224 patients with T2DM and in 102 nondiabetic individuals with metabolic syndrome. Plasma BA levels were measured with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) technique. Multivariable linear regression analyses were undertaken to assess associations between measured plasma BA species and T2DM status after adjustment for confounding factors. The presence of T2DM was significantly associated with higher plasma concentrations of both primary BAs (adjusted-standardized β coefficient: 0.279, p = 0.005) and secondary BAs (standardized β coefficient: 0.508, p < 0.001) after adjustment for age, sex, adiposity measures, serum alanine aminotransferase and use of statins or metformin. More specifically, the presence of T2DM was significantly associated with higher levels of plasma taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid and glycodeoxycholic acid (adjusted-standardized β coefficients ranging from 0.315 to 0.600; p < 0.01 or less), as well as with lower plasma levels of cholic acid (adjusted-standardized β coefficient: −0.250, p = 0.013) and taurocholic acid (adjusted-standardized β coefficient: −0.309, p = 0.001). This study shows that there are marked differences in plasma BA profiles between patients with and without T2DM. Further research will be needed to better understand how these differences in plasma BA profiles may interplay with the pathophysiology of T2DM.
Highlights
Bile acids (BAs) are cholesterol catabolites that are mainly synthesized in the liver [1]
The main findings of our cross-sectional study are as follows: (1) Ambulatory patients with type 2 diabetes mellitus (T2DM) had significantly higher plasma levels of primary and secondary BAs compared with nondiabetic control individuals; (2) in particular, patients with T2DM had significantly higher plasma levels of taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), hyodeoxycholic acid (HDCA), glycodeoxycholic acid (GDCA), glycolithocholic acid (GLCA) and deoxycholic acid (DCA), but lower plasma
The currently available human studies have provided conflicting results, with some suggesting that plasma fasting levels of total BAs are similar between individuals with and those without T2DM [6,7,9] and others suggesting that only specific BA fractions are higher in people with T2DM than in nondiabetic control individuals [8,10,11]
Summary
Bile acids (BAs) are cholesterol catabolites that are mainly synthesized in the liver [1]. In the alternative pathway of BA synthesis, cholesterol is first converted to oxysterol prior to being 7α-hydroxylated by the enzymes CYP7B1 or CYP39A1 [1,2]. After these initial steps, several enzymatic reactions occur to generate two primary BAs, i.e., chenodeoxycholic acid (CDCA) and cholic acid (CA) [1,2]. BAs are actively reabsorbed by enterocytes in the terminal ileum to hepatocytes where they are taken up and reused [1] This process is highly efficient, a small proportion of BAs escapes the ileal uptake, is modified by intestinal microbiota and is passively reabsorbed in the colon [1,2]. The circulating BA pool is highly hydrophobic and mainly consists of CA, CDCA and DCA, which are present in a ratio of nearly 40:40:20 [2]
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