A new metabolomic signature in type-2 diabetes mellitus and its pathophysiology.
OBJECTIVE
The objective of the current study was to find a metabolic signature associated with the early manifestations of type-2 diabetes mellitus.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Inken
I
Padberg
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Erik
E
Peter
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Sandra
S
González-Maldonado
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Henning
H
Witt
Heidelberg University Hospital, Department of Internal Medicine III, Heidelberg, Germany.
Matthias
M
Mueller
Heidelberg University Hospital, Department of Internal Medicine III, Heidelberg, Germany.
Tanja
T
Weis
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Bianca
B
Bethan
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Volker
V
Liebenberg
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Jan
J
Wiemer
Heidelberg University Hospital, Department of Internal Medicine III, Heidelberg, Germany.
Hugo A
HA
Katus
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Dietrich
D
Rein
Metanomics Health GmbH and metanomics GmbH, Biomarker Program, Berlin, Germany.
Philipp
P
Schatz
D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D015777:Eicosanoids / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D005951:Glucose Tolerance Test; D006038:Glyoxylates / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D055432:Metabolomics; D008954:Models, Biological; D011236:Prediabetic State / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D000959:Antihypertensive Agents; D015777:Eicosanoids; D006038:Glyoxylates; D006595:Hexosamines; C031150:glyoxylic acid