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.

Original languageEnglish (US)
Pages (from-to)719-728
Number of pages10
JournalClinical Chemistry
Volume57
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Biomarkers
Medical problems
Type 2 Diabetes Mellitus
Cardiovascular Diseases
Proteins
Oxidation
Oxidative stress
United States Food and Drug Administration
Immunoassay
Hyperglycemia
Industry
Oxidative Stress
Heart Failure
Myocardial Infarction
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Borges, C., Oran, P. E., Buddi, S., Jarvis, J. W., Schaab, M. R., Rehder, D. S., ... Nelson, R. W. (2011). Building multidimensional biomarker views of type 2 diabetes on the basis of protein microheterogeneity. Clinical Chemistry, 57(5), 719-728. https://doi.org/10.1373/clinchem.2010.156976

Building multidimensional biomarker views of type 2 diabetes on the basis of protein microheterogeneity. / Borges, Chad; Oran, Paul E.; Buddi, Sai; Jarvis, Jason W.; Schaab, Matthew R.; Rehder, Douglas S.; Rogers, Stephen P.; Taylor, Thomas; Nelson, Randall W.

In: Clinical Chemistry, Vol. 57, No. 5, 05.2011, p. 719-728.

Research output: Contribution to journalArticle

Borges, Chad ; Oran, Paul E. ; Buddi, Sai ; Jarvis, Jason W. ; Schaab, Matthew R. ; Rehder, Douglas S. ; Rogers, Stephen P. ; Taylor, Thomas ; Nelson, Randall W. / Building multidimensional biomarker views of type 2 diabetes on the basis of protein microheterogeneity. In: Clinical Chemistry. 2011 ; Vol. 57, No. 5. pp. 719-728.
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