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. CONCLUSION: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.

journal_name

Clin Chem

journal_title

Clinical chemistry

authors

Borges CR,Oran PE,Buddi S,Jarvis JW,Schaab MR,Rehder DS,Rogers SP,Taylor T,Nelson RW

doi

10.1373/clinchem.2010.156976

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

719-28

issue

5

eissn

0009-9147

issn

1530-8561

pii

clinchem.2010.156976

journal_volume

57

pub_type

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