College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611130, China.
Beijing Key Laboratory and Joint Laboratory for International Cooperation of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, China.
Rapid Commun Mass Spectrom. 2020 Jun 30;34(12):e8779. doi: 10.1002/rcm.8779.
The prevalence of type 2 diabetes mellitus (T2DM) is increasing but its early diagnosis in high risk populations remains challenging using only fasting blood glucose (FBG) or hemoglobin A1c measurements. It is, therefore, important to search for an integrated biomarker for early diagnosis by determining metabolites associated with the progression of the disease.
We recruited 149 participants (51 T2DM patients, 50 individuals with impaired fasting glucose (IFG) and 48 normal glucose tolerance subjects). Their serum samples were analyzed based on a metabolomics approach using ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS). The changes in metabolites were profiled and evaluated using univariate and multivariate analyses. Furthermore, a biomarker model was established and the potential biomarkers were evaluated using binary logistic regression analysis and receiver operating characteristic analysis with AUC (area under the curve). Pathway analysis of differential metabolites was performed to reveal the important biological information.
Thirty-eight differential metabolites were identified as significantly associated with T2DM patients and 23 differential metabolites with IFG individuals, mainly amino acids, carnitines, and phospholipids. By evaluating 17 potential biomarkers, we defined a novel integrated biomarker consisting of 2-acetolactate, 2-hydroxy-2,4-pentadienoate, L-arabinose and L-glutamine. The AUCs of the integrated biomarker with IFG and T2DM patients were 0.874 and 0.994, respectively, which showed a superior diagnostic performance. The levels of 2-acetolactate and 2-hydroxy-2,4-pentadienoate were strongly positively correlated with FBG, while L-glutamine and L-arabinose were strongly negatively associated with FBG. After pathway analysis, it was suggested that the majority of the influenced metabolic pathways associated with diabetes referred to amino acid metabolism.
The integrated biomarker could diagnose IFG and T2DM with a superior diagnostic performance. This finding provides support for novel biomarkers in the diagnosis and treatment of diabetes.
2 型糖尿病（T2DM）的患病率正在增加，但仅使用空腹血糖（FBG）或糖化血红蛋白（HbA1c）测量值，在高危人群中进行早期诊断仍然具有挑战性。因此，通过确定与疾病进展相关的代谢物，寻找用于早期诊断的综合生物标志物非常重要。
我们招募了 149 名参与者（51 名 T2DM 患者、50 名空腹血糖受损（IFG）个体和 48 名正常糖耐量受试者）。他们的血清样本基于超高效液相色谱四极杆-Orbitrap 高分辨率精确质量质谱法（UHPLC/Q-Orbitrap HRMS）进行代谢组学分析。使用单变量和多变量分析对代谢物的变化进行分析和评估。此外，还建立了生物标志物模型，并使用二元逻辑回归分析和具有 AUC（曲线下面积）的接收器操作特征分析来评估潜在的生物标志物。对差异代谢物进行途径分析，以揭示重要的生物学信息。
鉴定出 38 种差异代谢物与 T2DM 患者显著相关，23 种差异代谢物与 IFG 个体显著相关，主要为氨基酸、肉碱和磷脂。通过评估 17 种潜在的生物标志物，我们定义了一种由 2-乙酰乳酸、2-羟基-2,4-戊二烯酸、L-阿拉伯糖和 L-谷氨酰胺组成的新型综合生物标志物。该综合生物标志物对 IFG 和 T2DM 患者的 AUC 分别为 0.874 和 0.994，表现出优异的诊断性能。2-乙酰乳酸和 2-羟基-2,4-戊二烯酸的水平与 FBG 呈强烈正相关，而 L-谷氨酰胺和 L-阿拉伯糖与 FBG 呈强烈负相关。经过途径分析，提示与糖尿病相关的大多数受影响代谢途径与氨基酸代谢有关。
综合生物标志物可用于诊断 IFG 和 T2DM，具有优异的诊断性能。这一发现为糖尿病的诊断和治疗提供了新的生物标志物支持。
