Plasma bile acid changes in type 2 diabetes correlated with insulin secretion in two-step hyperglycemic clamp
Plasma bile acid changes in type 2 diabetes correlated with insulin secretion in two-step hyperglycemic clamp
复制标题
两步高血糖钳夹中 2 型糖尿病血浆胆汁酸变化与胰岛素分泌相关
DOI：
10.1111/1753-0407.12771
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发表时间：
2018-11-01
影响因子：
4.5
通讯作者：
Zhang, Yifei
中科院分区：
文献类型：
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作者：
Wang, Shujie;Deng, Yuying;Zhang, Yifei
背景：胆汁酸(BAs)在人体新陈代谢中传导重要信号。血浆BA浓度的变化、胰岛素分泌缺陷和人类2型糖尿病(T2 DM)进展之间的相关性还没有得到充分的研究。本研究探讨人血浆BA浓度在两步高血糖钳夹试验中的变化轨迹及其与胰岛素分泌动力学的关系。方法：11例正常糖耐量(NGT)健康受试者和33例未服药的T2 DM受试者。两步高血糖钳夹包括经典的第一步钳夹与禁食的第一步钳夹，然后是摄入碳水化合物餐后的第二步钳夹，说明基础的和胰岛素放大的胰岛素对葡萄糖的反应。采用高效液相色谱-串联质谱法测定血浆中BA含量。结果：与NGT组比较，T2 DM组熊去氧胆酸(UDCA)降低，石胆酸(LCA)和牛磺胆酸(TCA)升高。T2 DM患者血浆UDCA浓度和UDCA/LCA比值的动态变化与胰岛素分泌呈正相关，并在治疗后得到纠正。空腹UDCA/LCA和未结合/结合BA比值与T2 DM患者胰岛素分泌第一时相相关。结论：T2 DM患者BA成分异常及其与胰岛素分泌的相关性提示BA信号与胰岛素分泌能力之间存在交互作用，可利用空腹血浆BA成分指标预测和评估T2 DM的进展和预后。
Background: Bile acids (BAs) conduct crucial signals in human metabolism. Correlations between changes in plasma BA concentrations, insulin secretion defects, and progression of type 2 diabetes mellitus (T2DM) in humans have not been sufficiently investigated. This study explored the trajectories of changes in human plasma BA concentrations and their association with insulin secretion dynamics during a two-step hyperglycemic clamp.Methods: Eleven healthy subjects with normal glucose tolerance (NGT) and 33 drug-naive T2DM subjects were enrolled in the study. The two-step hyperglycemic clamp consisted of a classic clamp as Step 1 with fasting, followed by a Step 2 clamp after ingestion of a carbohydrate meal, illustrating basal and incretin-amplified insulin responses to glucose. Plasma BA were assayed using liquid chromatography-tandem mass spectrometry. Nine T2DM subjects were followed-up, and the two-step clamp was repeated after 3 months sulfonylurea treatment.Results: Ursodeoxycholic acid (UDCA) was lower and lithocholic acid (LCA) and taurocholic acid (TCA) were higher in T2DM compared with NGT subjects. The dynamics of plasma UDCA concentrations and the UDCA/LCA ratio was positively correlated with insulin secretion in T2DM subjects and were corrected after treatment. Moreover, fasting ratios of UDCA/LCA and unconjugated/conjugated BAs were correlated with the first phase of insulin secretion in T2DM subjects.Conclusion: The abnormal BA composition in T2DM subjects and its correlation with insulin secretion during the clamp suggest an interaction between BA signals and insulin secretion capacity, and the potential to use fasting plasma BA composition indices to predict and evaluate the progression and prognosis of T2DM.