Taylor David R, Alaghband-Zadeh Jamshid, Cross Gemma F, Omar Sohail, le Roux Carel W, Vincent Royce P
Department of Clinical Biochemistry, King's College Hospital, London, United Kingdom.
PLoS One. 2014 Apr 15;9(4):e93540. doi: 10.1371/journal.pone.0093540. eCollection 2014.
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.
胆汁酸是重要的内分泌信号分子,通过激活细胞表面和核受体来调节葡萄糖稳态。2型糖尿病患者的胆汁酸代谢会发生改变;然而,其是否具有致病后果尚未完全明确。在本研究中,对2型糖尿病患者和匹配的健康志愿者的尿胆汁酸排泄情况进行了评估。2型糖尿病患者的尿胆汁酸排泄情况是在当前血糖水平和患者体重指数的背景下进行考量的。采用液相色谱 - 串联质谱法测定尿胆汁酸,可对15种胆汁酸进行个体定量分析。体重正常(BMI 18.5 - 24.9 kg/m²)和超重(BMI 25 - 29.9 kg/m²)的2型糖尿病患者的尿胆汁酸排泄量高于健康体重正常的志愿者,两者p均<0.0001。肥胖(BMI≥30 kg/m²)的2型糖尿病患者的尿胆汁酸排泄量显著低于体重正常和超重的2型糖尿病组(两者p均<0.01)。总胆汁酸排泄量在体重正常(rs = 0.85,p =<0.001)和超重(rs = 0.61,p = 0.02)的2型糖尿病患者中与糖化血红蛋白呈正相关,但在肥胖的2型糖尿病患者中无相关性(rs = -0.08,p = 0.73)。本研究中观察到的体重正常和超重的2型糖尿病患者中与血糖相关的尿胆汁酸排泄增加可能代表胆汁酸信号传导的代偿性增加,以维持葡萄糖稳态。由于肥胖似乎使这种改变减弱;因此有必要进一步研究胆汁酸信号传导对2型糖尿病发病机制的体重依赖性影响。