Soluble Tumor Necrosis Factor Receptor 2 Is Independently Associated With Brachial-Ankle Pulse-Wave Velocity in Nonobese Japanese Type 2 Diabetic Patients
- Minako Ohgushi, MD1,
- Ataru Taniguchi, MD1,
- Mitsuo Fukushima, MD2,
- Yoshikatsu Nakai, MD3,
- Akira Kuroe, MD1,
- Michihiro Ohya, MD1 and
- Yutaka Seino, MD1
- 1Division of Diabetes and Clinical Nutrition, Kansai-Denryoku Hospital, Osaka, Japan
- 2Department of Health Informatics Research, Translational Research Informatics Center, Kobe, Japan
- 3Karasuma-Nakai Clinic, Kyoto, Japan
- Address correspondence to Ataru Taniguchi, MD, Division of Diabetes and Clinical Nutrition, Kansai-Denryoku Hospital, 2-1-7 Fukushima, Fukushima-ku, Osaka-city, Osaka 553-0003, Japan. E-mail: taniguchi.ataru{at}a5.kepco.co.jp
Type 2 diabetes is associated with high mortality and morbidity due to atherosclerosis. Biermen (1) estimated that typical risk factors, including blood pressure, cholesterol, and smoking, can account for no more than 30% of excess cardiovascular risk factor in diabetic patients. Thus, other factors seem to play a role in the progression of atherosclerosis in diabetes.
Aortic stiffness measured by pulse- wave velocity (PWV) is shown to be highly predictive of cardiovascular mortality in type 2 diabetic patients (2). While age and blood pressure are shown to be associated with PWV, age and blood pressure alone do not completely account for the abnormalities of aortic stiffness in type 2 diabetic patients.
Tumor necrosis factor (TNF) system activity seems to be associated with the progression of atherosclerosis in type 2 diabetes. Shai et al. (3) demonstrated that soluble TNF receptor 2 (sTNF-R2) is strongly associated with risk of coronary heart disease in type 2 diabetic patients. We showed that sTNF-R1 is associated with albuminuria in type 2 diabetic patients (4). To the best of our knowledge, however, it is unclear whether PWV is associated with TNF system activity in type 2 diabetic patients. The aim of the present study, therefore, was to investigate the relationships between PWV and TNF receptors in type 2 diabetic patients.
Eighty-six nonobese Japanese type 2 diabetic patients were enrolled. Their age, BMI, HbA1c (A1C), systolic and diastolic blood pressure, and serum creatinine were 62.8 ± 1.0 years, 22.8 ± 0.3 kg/m2, 7.0 ± 0.1%, 136 ± 2 mmHg, 82 ± 1 mmHg, and 0.76 ± 0.02 mg/dl, respectively. They had not been treated with insulin. Thirty-four patients were treated with antihypertensive medications. In conjunction with PWV, systolic and diastolic blood pressure, A1C, glucose, lipids, serum creatinine, TNF-α, sTNF-R1, and sTNF-R2 were measured after an overnight fast.
With univariate analysis, PWV was positively correlated to age (r = 0.492, P < 0.001), diabetes duration (r = 0.251, P = 0.021), systolic (r = 0.595, P < 0.001) and diastolic (r = 0.248, P = 0.022) blood pressure, antihypertensive medication (r = 0.268, P = 0.013), and the concentrations of sTNF-R1 (r = 0.354, P = 0.001) and sTNF-R2 (r = 0.415, P < 0.001). Other variables, including TNF-α, were not associated with PWV. Multiple regression analyses showed that PWV was independently predicted by age (F = 15.1), systolic blood pressure (F = 31.6), and sTNF-R2 (F = 5.2), which explained 49.2% of the variability of PWV. Thus, TNF system activity seems to be associated with atherosclerosis in nonobese Japanese type 2 diabetic patients.
