Diabetes is estimated to be the sixth leading cause of death in the U.S., and is found to occur disproportionately in minority populations. The prevalence of diabetes increased by ~ 50 % from 1990 to 2000, and is still on the rise. The estimated total national cost of diabetes in 2007 was $174 billion, the majority going directly to medical expenditures. In response to this epidemic, there are currently more than 350 candidate drugs in development making diabetes second only to cancer in health-related R&D focus. Considering that adverse cardiovascular events such as heart attack and stroke are the major causes of diabetes related deaths, the FDA recently issued a Guidance for Industry entitled, """"""""Diabetes Mellitus ~ Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes"""""""", which recommends that new clinical trials for type 2 antidiabetic therapies demonstrate that the therapy will not result in an unacceptable increase in cardiovascular risk. Currently there are no standard markers for cardiovascular risk in the context of type 2 diabetes. We have created a highly integrated, multidisciplinary research team specifically assembled to discover, validate and translate novel biomarkers for cardiovascular complications of type 2 diabetes for use within drug development. The envisioned biomarkers will better predict the onset of cardiovascular disease in the context of type 2 diabetes and help define the optimal therapeutic or pharmaceutical interventions to significantly improve patient outcomes.

Public Health Relevance

Long standing type 2 diabetes mellitus (T2DM) frequently results in cardiovascular disease (CVD) and associated adverse medical outcomes such as heart attack and stroke. Reports in the past few years have found no or limited correlation between T2DM treatment options and the reduction of CVD comorbidities in diabetic populations. Accordingly, there is an immediate and urgent need for the development of in vivo biomarkers of CVD risk and translation of new findings and technologies into antidiabetic drug development pipelines. Thus, the goal of this project is to establish the pathway for discovery, validation and translation of new biomarkers of cardiovascular risk in diabetes.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Resource-Related Research Projects (R24)
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Special Emphasis Panel (ZDK1-GRB-J (M1))
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Sechi, Salvatore
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Arizona State University-Tempe Campus
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Jeffs, Joshua W; Ferdosi, Shadi; Yassine, Hussein N et al. (2017) Ex vivo instability of glycated albumin: A role for autoxidative glycation. Arch Biochem Biophys 629:36-42
Yassine, Hussein N; Trenchevska, Olgica; Dong, Zhiwei et al. (2016) The association of plasma cystatin C proteoforms with diabetic chronic kidney disease. Proteome Sci 14:7
Koska, Juraj; Yassine, Hussein; Trenchevska, Olgica et al. (2016) Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes. J Lipid Res 57:894-905
Kinsky, Owen R; Hargraves, Tiffanie L; Anumol, Tarun et al. (2016) Metformin Scavenges Methylglyoxal To Form a Novel Imidazolinone Metabolite in Humans. Chem Res Toxicol 29:227-34
Trenchevska, Olgica; Yassine, Hussein N; Borges, Chad R et al. (2016) Development of quantitative mass spectrometric immunoassay for serum amyloid A. Biomarkers :1-9
Azizkhanian, Ida; Trenchevska, Olgica; Bashawri, Yara et al. (2016) Posttranslational modifications of apolipoprotein A-II proteoforms in type 2 diabetes. J Clin Lipidol 10:808-815
Trenchevska, Olgica; Nelson, Randall W; Nedelkov, Dobrin (2016) Mass spectrometric immunoassays for discovery, screening and quantification of clinically relevant proteoforms. Bioanalysis 8:1623-1633
Trenchevska, Olgica; Sherma, Nisha D; Oran, Paul E et al. (2015) Quantitative mass spectrometric immunoassay for the chemokine RANTES and its variants. J Proteomics 116:15-23
Kimzey, Michael J; Kinsky, Owen R; Yassine, Hussein N et al. (2015) Site specific modification of the human plasma proteome by methylglyoxal. Toxicol Appl Pharmacol 289:155-62
Yassine, Hussein N; Trenchevska, Olgica; Ramrakhiani, Ambika et al. (2015) The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides. PLoS One 10:e0144138

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