NASH-related increases in plasma bile acid levels depend on insulin resistance

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Grzych, Guillaume | Chávez-Talavera, Oscar | Descat, Amandine | Thuillier, Dorothée | Verrijken, An | Kouach, Mostafa | Legry, Vanessa | Verkindt, Hélène | Raverdy, Violeta | Legendre, Benjamin | Caiazzo, Robert | van Gaal, Luc | Goossens, Jean-Francois | Paumelle, Réjane | Francque, Sven | Pattou, François | Haas, Joel, T. | Tailleux, Anne | Staels, Bart

Edité par CCSD ; Elsevier -

International audience. Introduction: Plasma bile acids (BA) have been extensively studied as pathophysiological actors in Non-Alcoholic Steatohepatitis (NASH). However, results from clinical studies are often complicated by the association of NASH with type 2 diabetes (T2D), obesity and insulin resistance (IR). Here, we sought to dissect the relationship between NASH, T2D and plasma BA levels in a large patient cohort. Materials and Methods: Four groups of patients from the ABOS cohort (Clin Trials NCT01129297) were included based on presence or absence of histologically evaluated NASH with or without coincident T2D. Patients were matched for BMI, HOMA2-assessed IR, HbA 1c , age and gender. To study the effect of IR and BMI on the association of plasma BA and NASH, patients from the Hepadip study were included. In both cohorts, fasting plasma BA concentrations were measured. Results: Plasma BA concentrations were higher in NASH compared to No-NASH patients both in T2D and NoT2D patients from the ABOS cohort. As we previously reported that plasma BA levels were unaltered in NASH patients of the Hepadip cohort, we assessed the impact of BMI and IR on the association of NASH and BA on the combined BA datasets. Our results revealed that NASH-associated increases in plasma total cholic acid (CA) concentrations depend on the degree of HOMA2-assessed systemic IR, but not on -cell function nor on BMI.

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