Elevated Serum Osteoprotegerin Levels Are Associated With Vascular Endothelial Dysfunction in Type 2 Diabetes

  1. Jang Yel Shin, MD,
  2. Young Goo Shin, MD, PHD and
  3. Choon Hee Chung, MD, PHD
  1. Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Kangwon-Do, Korea
  1. Address correspondence and reprint requests to Choon Hee Chung, MD, Department of Internal Medicine, Wonju College of Medicine, Yonsei University, 162 Ilsan-Dong, Wonju-Si, Kangwon-Do, Korea, 220-701. E-mail: cchung{at}yonsei.ac.kr

The majority of diabetes-related mortalities are due to macrovascular complications (1). The early detection of atherosclerotic complications is important in reducing mortality and morbidity from cardiovascular events (2). Endothelial dysfunction is an early process in atherosclerosis and a predictor of cardiovascular events (3,4). Furthermore, endothelial dysfunction is detectable by measuring the flow-mediated dilation (FMD) of the brachial artery (5).

Osteoprotegerin (OPG) is a key cytokine that belongs to the tumor necrosis factor receptor family and inhibits RANKL (receptor activator of nuclear factor κB ligand)–mediated osteoclastic bone resorption (6,7). OPG is expressed in various tissues (8). In endothelial cells, OPG may act as an antiapoptotic factor by binding to the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) (9,10).

OPG knockout mice develop vascular calcification and osteoporosis (11). Epidemiologic studies have suggested that serum OPG levels are correlated with age, diabetes, hypertension, cardiovascular mortality (12), and the presence and severity of coronary artery disease (13,14). However, the relationship between OPG and endothelial dysfunction has not been proven. In this study, we evaluated the relationship between serum OPG levels and endothelial dysfunction in type 2 diabetes.


We enrolled 104 type 2 diabetic patients (mean age 53.1 ± 8.1 years, 67.6% male) using the following exclusion criteria: 1) a history of myocardial infarction, angina, stroke, or peripheral artery disease; 2) presence of carotid stenosis ≥30%; 3) ankle-brachial …

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