type-2 diabetes mellitus.\r\nResearch Design and Method: Modern metabolic profiling technology (MxPTM Broad Profiling) was applied to find early\r\nalterations in the plasma metabolome of type-2 diabetic patients. The results were validated in an independent study.\r\nEicosanoid and single inon monitoring analysis (MxPTM Eicosanoid and MxPTM SIM analysis) were performed in subsets of\r\nsamples.\r\nResults: A metabolic signature including significantly increased levels of glyoxylate as a potential novel marker for early\r\ndetection of type-2 diabetes mellitus was identified in an initial study (Study1). The signature was significantly altered in\r\nfasted diabetic and pre-diabetic subjects and in non-fasted subjects up to three years prior to the diagnosis of type-2\r\ndiabetes; most alterations were also consistently found in an independent patient group (Study 2). In Study 2 diabetic and\r\nmost control subjects suffered from heart failure. In Study 1 a subgroup of diabetic subjects, with a history of use of antihypertensive\r\nmedication further showed a more pronounced increase of glyoxylate levels, compared to a non-diabetic\r\ncontrol group when tested in a hyperglycemic state. In the context of a prior history of anti-hypertensive medication,\r\nalterations in hexosamine and eicosanoid levels were also found.\r\nConclusion: A metabolic signature including glyoxylate was associated with type-2 diabetes mellitus, independent of the\r\nfasting status and of occurrence of another major disease. The same signature was also found to be associated with prediabetic\r\nsubjects. Glyoxylate levels further showed a specifically strong increase in a subgroup of diabetic subjects. It could\r\nrepresent a new marker for the detection of medical subgroups of diabetic subjects.
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