Correlation of Plasma Endothelial Cell Activity With Cardiovascular Events in Patients With Diabetes Mellitus Type 2
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|ClinicalTrials.gov Identifier: NCT00252525|
Recruitment Status : Completed
First Posted : November 11, 2005
Last Update Posted : June 27, 2014
CSP 465-B, Correlation of Plasma Endothelial Cell (Basic Fibroblast Growth Factor) Activity With Cardiovascular Events in Patients with Diabetes Mellitus, Type II.
Mark Zimering M.D.
Objectives: Endothelial cell dysfunction plays a role in the development of the atherosclerotic vascular lesion and it is also thought to provide a mechanism for increased urinary albumin excretion in type 2 diabetes mellitus. Micro- or macroalbuminuria are associated with increased cardiovascular (CV) morbidity and mortality in type 2 diabetes mellitus. In at least one longitudinal study in older-age onset patients, micro-or macroalbuminuria robustly predicted increased CV risk independent of other diabetes-related factors.1 The pathogenetic mechanisms underlying a significant association between micro- or macroalbuminuria and CV risk in diabetes mellitus are not known but may include: growth factors, clotting factors, lipids, or hemodynamic factors. The aim of the present study is to investigate whether an angiogenic growth factor, basic fibroblast growth factor (bFGF), plays a role in increased CV risk in type 2 diabetes mellitus. Research Plan: BFGF (FGF-2) is one of the most potent known angiogenesis factors. Increased bFGF was previously associated with both endothelial cell injury and micro- or macroalbuminuria. In a prior study of 73 older-age onset veterans with type 2 diabetes mellitus (JCEM, 1996), we found plasma endothelial cell (bFGF) activity was significantly associated with glycemic levels, and (in multiple regression analysis) independently associated with both microalbuminuria and retinopathy. We will test whether plasma endothelial cell (bFGF) activity is significantly, independently associated with a pooled endpoint of cardiovascular events that includes myocardial infarction (MI), coronary revascularization, congestive heart failure (CHF), or CV mortality. We expect that increased bFGF may itself be a robust marker for increased CV risk in diabetes mellitus for three reasons. First, because bFGF was independently associated with (micro)-albuminuria in type 2 diabetes mellitus. Second, because increased bFGF was associated with increased activity in the renin-angiotensin system in vascular smooth muscle cells (Dzau, et al. JCI, 1995). And third, because (as we reported) angiotensin converting enzyme inhibitor (ACEi) drugs substantially decreased plasma bFGF levels in (micro)- albuminuric diabetes mellitus type 2, and (as others reported) ACEi drugs substantially reduced the risk of development of CHF in patients with LVH 2, the risk of mortality after MI (8,9), and the risk of CV death in diabetic patients with proteinuria.
Because plasma endothelial cell (bFGF) activity correlated significantly with glycemic levels in diabetes mellitus type 2, plasma bFGF may be one of the pathogenetic links between glycemic levels and an increased risk of cardiovascular events in diabetes mellitus, type 2.
Methods: Blood (3 mL EDTA plasma) will be collected from each subject in Years 1, and 2 of the Study at each of 6 local participating VA substudy sites. Because plasma endothelial cell (bFGF-like) bioactivity and bFGFR-IR in vivo are stable for months and years based on our prior published studies (1-3), we anticipate that obtaining 2 specimens, 1 each in Years 1, 2 of the study, will provide sufficient data to model proportional risk.
|Condition or disease|
|Type 2 Diabetes Mellitus|
Show Detailed Description
|Study Type :||Observational|
|Actual Enrollment :||400 participants|
|Official Title:||CSP #465B - Correlation of Plasma Endothelial Cell (Basic Fibroblast Growth Factor) Activity With Cardiovascular Events In Patients With Diabetes Mellitus Type 2|
|Study Start Date :||June 2007|
|Actual Primary Completion Date :||May 2008|
|Actual Study Completion Date :||May 2008|
This is an observational study of patients who are enrolled in the ongoing randomized clinical trial AGlycemic Control and Complications in Diabetes Mellitus Type 2@.
- The primary outcome measures are cardiovascular morbidity and mortality. [ Time Frame: End of study. ]
Biospecimen Retention: None Retained
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00252525
|United States, Arizona|
|Carl T. Hayden VA Medical Center|
|Phoenix, Arizona, United States, 85012|
|United States, California|
|VA Medical Center, Long Beach|
|Long Beach, California, United States, 90822|
|United States, Florida|
|Miami VA Healthcare System, Miami, FL|
|Miami, Florida, United States, 33125|
|United States, Nebraska|
|VA Medical Center, Omaha|
|Omaha, Nebraska, United States, 68105-1873|
|United States, New Jersey|
|VA New Jersey Health Care System, East Orange|
|East Orange, New Jersey, United States, 07018|
|United States, Texas|
|VA South Texas Health Care System, San Antonio|
|San Antonio, Texas, United States, 78229|
|United States, Virginia|
|Hunter Holmes McGuire VA Medical Center|
|Richmond, Virginia, United States, 23249|
|Study Chair:||Carlos Abraira, MD||Miami VA Healthcare System, Miami, FL|