Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

• Published in: Nutrition & metabolism Vol. 8; no. 1; pp. 48 - 344
• Main Authors: Cariou, Bertrand, Chetiveaux, Maud, Zaïr, Yassine, Pouteau, Etienne, Disse, Emmanuel, Guyomarc'h-Delasalle, Béatrice, Laville, Martine, Krempf, Michel
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.07.2011; BioMed Central Ltd; BMC
• Subjects: adults; Bile acids; blood glucose; blood lipids; Blood sugar; body mass index; Brief Communication; calorimetry; Chenodeoxycholic acid; Cholic acid; Clinical Nutrition; deoxycholic acid; energy expenditure; Food and Nutrition; FXR; gas chromatography; gender; glucose; glucose tolerance; homeostasis; Human health and pathology; humans; hyperinsulinemic-euglycemic clamp; insulin; insulin resistance; Life Sciences; lipid content; lipids; mass spectrometry; Medicine; Medicine & Public Health; Metabolic Diseases; mice; multivariate analysis; noninsulin-dependent diabetes mellitus; patients; Physiological aspects; TGR5; Tissues and Organs; type 2 diabetes; volunteers; France; FXR; TGR5; type 2 diabetes; bile acids; hyperinsulinemic-euglycemic clamp; energy expenditure; insulin resistance
• ISSN: 1743-7075; 1743-7075
• DOI: 10.1186/1743-7075-8-48

Background Accumulating data suggest a novel role for bile acids (BAs) in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans. Findings Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D), and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR) during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects). Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001), CA (β = 0.03, p = 0.09) and DCA concentrations (β = 0.07, p < 0.0001). Spearman analysis retrieved an inverse relationship between plasma CDCA (r = -0.44, p = 0.03), CA (r = -0.65, p = 0.001) and the GIR. HOMA-IR remained positively associated with CDCA (β = 0.11, p = 0.01), CA (β = 0.04, p = 0.01) and DCA (β = 0.06, p = 0.007) in multivariable analysis, after adjustment for age, gender, BMI, HbA1C and plasma lipid parameters. In contrast, HbA1c, energy expenditure and plasma lipid concentrations were not correlated with plasma BAs levels in multivariable analysis. Conclusions Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.