title: Urine bile acids relate to glucose control in patients with type 2 diabetes mellitus and a body mass index below 30 kg/m2.
abstract: Bile acids are important endocrine signalling molecules, modulating glucose homeostasis through activation of cell surface and nuclear receptors. Bile acid metabolism is altered in type 2 diabetes mellitus; however, whether this is of pathogenic consequence is not fully established. In this study urinary bile acid excretion in individuals with type 2 diabetes and matched healthy volunteers was assessed. Urinary bile acid excretion in type 2 diabetes patients was considered in the context of prevailing glycaemia and the patient body mass index. Urine bile acids were measured by liquid chromatography-tandem mass spectrometry, allowing individual quantification of 15 bile acid species. Urinary bile acid excretion in patients with type 2 diabetes who were normal weight (BMI 18.5-24.9 kg/m2) and overweight (BMI 25-29.9 kg/m2) were elevated compared to healthy normal weight volunteers, both p<0.0001. In obese (BMI ≥ 30 kg/m2) type 2 diabetes patients, urinary bile acid excretion was significantly lower than in the normal and overweight type 2 diabetes groups (both p<0.01). Total bile acid excretion positively correlated with HbA1c in normal (rs=0.85, p=<0.001) and overweight (rs=0.61, p=0.02) but not obese type 2 diabetes patients (rs=-0.08, p=0.73). The glycaemia-associated increases in urine bile acid excretion in normal weight and overweight type 2 diabetes seen in this study may represent compensatory increases in bile acid signalling to maintain glucose homeostasis. As such alterations appear blunted by obesity; further investigation of weight-dependent effects of bile acid signalling on type 2 diabetes pathogenesis is warranted.
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
authors.forename: David R
authors.initials: DR
authors.lastname: Taylor
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Alaghband-Zadeh
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
authors.forename: Gemma F
authors.initials: GF
authors.lastname: Cross
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
authors.forename: Sohail
authors.initials: S
authors.lastname: Omar
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
authors.forename: Carel W
authors.initials: CW
authors.lastname: le Roux
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
authors.forename: Royce P
authors.initials: RP
authors.lastname: Vincent
mesh_terms: D000368:Aged; D001647:Bile Acids and Salts / Q000652:urine*; D001786:Blood Glucose; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006002:Glycodeoxycholic Acid / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D006002:Glycodeoxycholic Acid
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