Padberg Inken, Peter Erik, González-Maldonado Sandra, Witt Henning, Mueller Matthias, Weis Tanja, Bethan Bianca, Liebenberg Volker, Wiemer Jan, Katus Hugo A, Rein Dietrich, Schatz Philipp
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Heidelberg University Hospital, Department of Internal Medicine III, Heidelberg, Germany.
PLoS One. 2014 Jan 17;9(1):e85082. doi: 10.1371/journal.pone.0085082. eCollection 2014.
The objective of the current study was to find a metabolic signature associated with the early manifestations of type-2 diabetes mellitus.
Modern metabolic profiling technology (MxP™ Broad Profiling) was applied to find early alterations in the plasma metabolome of type-2 diabetic patients. The results were validated in an independent study. Eicosanoid and single inon monitoring analysis (MxP™ Eicosanoid and MxP™ SIM analysis) were performed in subsets of samples.
A metabolic signature including significantly increased levels of glyoxylate as a potential novel marker for early detection of type-2 diabetes mellitus was identified in an initial study (Study1). The signature was significantly altered in fasted diabetic and pre-diabetic subjects and in non-fasted subjects up to three years prior to the diagnosis of type-2 diabetes; most alterations were also consistently found in an independent patient group (Study 2). In Study 2 diabetic and most control subjects suffered from heart failure. In Study 1 a subgroup of diabetic subjects, with a history of use of anti-hypertensive medication further showed a more pronounced increase of glyoxylate levels, compared to a non-diabetic control group when tested in a hyperglycemic state. In the context of a prior history of anti-hypertensive medication, alterations in hexosamine and eicosanoid levels were also found.
A metabolic signature including glyoxylate was associated with type-2 diabetes mellitus, independent of the fasting status and of occurrence of another major disease. The same signature was also found to be associated with pre-diabetic subjects. Glyoxylate levels further showed a specifically strong increase in a subgroup of diabetic subjects. It could represent a new marker for the detection of medical subgroups of diabetic subjects.
本研究的目的是寻找与2型糖尿病早期表现相关的代谢特征。
应用现代代谢谱分析技术（MxP™全谱分析）来发现2型糖尿病患者血浆代谢组的早期变化。研究结果在一项独立研究中得到验证。对部分样本进行了类花生酸和单离子监测分析（MxP™类花生酸分析和MxP™单离子监测分析）。
在初步研究（研究1）中，确定了一种代谢特征，其中包括作为2型糖尿病早期检测潜在新标志物的乙醛酸水平显著升高。在空腹糖尿病患者和糖尿病前期患者以及在诊断为2型糖尿病前长达三年的非空腹受试者中，该特征有显著改变；在一个独立的患者组（研究2）中也一致发现了大多数变化。在研究2中，糖尿病患者和大多数对照受试者患有心力衰竭。在研究1中，有使用抗高血压药物病史的糖尿病患者亚组，与非糖尿病对照组相比，在高血糖状态下测试时乙醛酸水平进一步显著升高。在有抗高血压药物使用史的背景下，还发现了己糖胺和类花生酸水平的变化。
包括乙醛酸的代谢特征与2型糖尿病相关，与空腹状态和另一种重大疾病的发生无关。同样的特征也与糖尿病前期受试者相关。乙醛酸水平在糖尿病患者亚组中进一步显示出特别强烈的升高。它可能代表一种用于检测糖尿病患者医学亚组的新标志物。
