Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients
Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients
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DOI：
10.3390/metabo9090184
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发表时间：
2019-09-01
期刊：
影响因子：
4.1
通讯作者：
Hyotylainen, Tuulia
中科院分区：
文献类型：
--
作者：
Ahonen, Linda;Jantti, Sirkku;Hyotylainen, Tuulia
文献中已经报道了几种小分子生物标志物用于预测和诊断（前期）糖尿病、其合并症和并发症。在这里，我们报告了一种新的定量方法的开发和验证，用于测定从人血浆中选择的34种代谢物生物标志物。我们选择了一组代谢物，表明糖尿病的各种临床相关的致病阶段。我们将这些候选生物标志物合并到一个单一的超高效液相色谱-串联质谱（UHPLC-MS/MS）方法中，并对其进行优化，优先考虑样品制备的简单性和分析所需的时间，从而实现临床实验室环境下的高通量分析。我们从检出限（LOD）和定量限（LOQ）、线性（R-2）以及每种代谢物的日内和日内重复性等方面验证了该方法。该方法的性能在分析糖尿病队列研究的选定样本中得到了证明。代谢物水平与1型糖尿病（T1D）患者的临床测量和肾脏并发症相关。具体来说，氨基酸和氨基酸相关分析物，以及特定胆汁酸，都与大量蛋白尿有关。此外，特异性胆汁酸与血糖控制、抗高血压药物、他汀类药物和临床脂质测量有关。该分析方法适用于糖尿病临床中选定血浆代谢物的稳健测定。
Several small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities, and complications. Here, we report the development and validation of a novel, quantitative method for the determination of a selected panel of 34 metabolite biomarkers from human plasma. We selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings. We validated the method in terms of limits of detection (LOD) and quantitation (LOQ), linearity (R-2), and intra- and inter-day repeatability of each metabolite. The method's performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes, as well as specific bile acids, were associated with macro-albuminuria. Additionally, specific bile acids were associated with glycemic control, anti-hypertensive medication, statin medication, and clinical lipid measurements. The developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic.