title: Validation of a metabolite panel for early diagnosis of type 2 diabetes.
abstract: BACKGROUND
  Accurate, early diagnosis of type 2 diabetes (T2D) would enable more effective clinical management and a reduction in T2D complications. Therefore, we sought to identify plasma metabolite and protein biomarkers that, in combination with glucose, can better predict future T2D compared with glucose alone.
  
  
  METHODS
  In this case-control study, we used plasma samples from the Bavarian Red Cross Blood Transfusion Center study (61 T2D cases and 78 non-diabetic controls) for discovering T2D-associated metabolites, and plasma samples from the Personalized Medicine Research Project in Wisconsin (56 T2D cases and 445 non-diabetic controls) for validation. All samples were obtained before or at T2D diagnosis. We tested whether the T2D-associated metabolites could distinguish incident T2D cases from controls, as measured by the area under the receiver operating characteristic curve (AUC). Additionally, we tested six metabolic/pro-inflammatory proteins for their potential to augment the ability of the metabolites to distinguish cases from controls.
  
  
  RESULTS
  A panel of 10 metabolites discriminated better between T2D cases and controls than glucose alone (AUCs: 0.90 vs 0.87; p=2.08×10(-5)) in Bavarian samples, and associations between these metabolites and T2D were confirmed in Wisconsin samples. With use of either a Bayesian network classifier or ridge logistic regression, the metabolites, with or without the proteins, discriminated incident T2D cases from controls marginally better than glucose in the Wisconsin samples, although the difference in AUCs was not statistically significant. However, when the metabolites and proteins were added to two previously reported T2D prediction models, the AUCs were higher than those of each prediction model alone (AUCs: 0.92 vs 0.87; p=3.96×10(-2) and AUCs: 0.91 vs 0.71; p=1.03×10(-5), for each model, respectively).
  
  
  CONCLUSIONS
  Compared with glucose alone or with previously described T2D prediction models, a panel of plasma biomarkers showed promise for improved discrimination of incident T2D, but more investigation is needed to develop an early diagnostic marker.
authors: Center for Human Genetics, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, Marshfield, WI, 54449, USA. Electronic address: carter.tonia@mcrf.mfldclin.edu.
authors: Tonia C
authors: TC
authors: Carter
authors: Metanomics Health GmbH, Tegeler Weg 33, 10589, Berlin, Germany. Electronic address: dietrich.rein@metanomics-health.de.
authors: Dietrich
authors: D
authors: Rein
authors: Center for Stroke Research Berlin, Charitéplatz 1, 10117, Berlin, Germany. Electronic address: inken.padberg@charite.de.
authors: Inken
authors: I
authors: Padberg
authors: metanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany. Electronic address: erik.peter@metanomics.de.
authors: Erik
authors: E
authors: Peter
authors: metanomics GmbH, Tegeler Weg 33, 10589, Berlin, Germany. Electronic address: ulrike.rennefahrt@metanomics.de.
authors: Ulrike
authors: U
authors: Rennefahrt
authors: Integrated Research and Development Laboratory, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, Marshfield, WI, 54449, USA. Electronic address: david.donna@mcrf.mfldclin.edu.
authors: Donna E
authors: DE
authors: David
authors: Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, Marshfield, WI, 54449, USA. Electronic address: valeriedmcmanus@gmail.com.
authors: Valerie
authors: V
authors: McManus
authors: Integrated Research and Development Laboratory, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, Marshfield, WI, 54449, USA. Electronic address: stefanski.elisha@mcrf.mfldclin.edu.
authors: Elisha
authors: E
authors: Stefanski
authors: Blutspendedienst des Bayerischen Roten Kreuzes Gemeinnützige GmbH, Herzog-Heinrich-Strasse 2, 80336, München, Germany. Electronic address: s.martin@blutspendedienst.com.
authors: Silke
authors: S
authors: Martin
authors: Metanomics Health GmbH, Tegeler Weg 33, 10589, Berlin, Germany. Electronic address: philipp.schatz@metanomics-health.de.
authors: Philipp
authors: P
authors: Schatz
authors: Center for Human Genetics, Marshfield Clinic Research Foundation, 1000 North Oak Avenue, Marshfield, WI, 54449, USA. Electronic address: schrodi.steven@mcrf.mfldclin.edu.
authors: Steven J
authors: SJ
authors: Schrodi
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis; D011237:Predictive Value of Tests; D012372:ROC Curve; D012016:Reference Values
chemical_list: D015415:Biomarkers; D001786:Blood Glucose
keywords: Biomarker; Diabetes; Glucose; Metabolomics; Predictive modeling