title: Building multidimensional biomarker views of type 2 diabetes on the basis of protein microheterogeneity.
abstract: BACKGROUND
  In 2008, the US Food and Drug Administration (FDA) issued a Guidance for Industry statement formally recognizing (during drug development) the conjoined nature of type 2 diabetes (T2D) and cardiovascular disease (CVD), which has precipitated an urgent need for panels of markers (and means of analysis) that are able to differentiate subtypes of CVD in the context of T2D. Here, we explore the possibility of creating such panels using the working hypothesis that proteins, in addition to carrying time-cumulative marks of hyperglycemia (e.g., protein glycation in the form of Hb A(₁c)), may carry analogous information with regard to systemic oxidative stress and aberrant enzymatic signaling related to underlying pathobiologies involved in T2D and/or CVD.
  
  
  METHODS
  We used mass spectrometric immunoassay to quantify, in targeted fashion, relative differences in the glycation, oxidation, and truncation of 11 specific proteins.
  
  
  RESULTS
  Protein oxidation and truncation (owing to modified enzymatic activity) are able to distinguish between subsets of diabetic patients with or without a history of myocardial infarction and/or congestive heart failure where markers of glycation alone cannot.
  
  
  CONCLUSIONS
  Markers based on protein modifications aligned with the known pathobiologies of T2D represent a reservoir of potential cardiovascular markers that are needed to develop the next generation of antidiabetes medications.
authors.affiliation: Molecular Biomarkers, The Biodesign Institute at Arizona State University, Tempe, AZ, USA.
authors.forename: Chad R
authors.initials: CR
authors.lastname: Borges
authors.forename: Paul E
authors.initials: PE
authors.lastname: Oran
authors.forename: Sai
authors.initials: S
authors.lastname: Buddi
authors.forename: Jason W
authors.initials: JW
authors.lastname: Jarvis
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Schaab
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Rehder
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Rogers
authors.forename: Thomas
authors.initials: T
authors.lastname: Taylor
authors.forename: Randall W
authors.initials: RW
authors.lastname: Nelson
mesh_terms: D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D006031:Glycosylation; D006333:Heart Failure / Q000097:blood / Q000150:complications; D006801:Humans; D007118:Immunoassay; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications; D010084:Oxidation-Reduction; D017354:Point Mutation; D025341:Principal Component Analysis; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D020543:Proteome