Coronary artery calcification, arterial stiffness and renal insufficiency associate with serum levels of tumor necrosis factor-alpha in Japanese type 2 diabetic patients

Although the kidneys are the major source of proinflammatory cytokines, association of tumor necrosis factor-alpha (TNF-α) with severity of atherosclerosis or kidney function in diabetic patients is unclear. Two hundred type 2 diabetic patients and 30 age-matched nondiabetic subjects consecutively admitted to our hospital were enrolled. The Agatston coronary artery calcium score (CACS), a quantitative marker of coronary atherosclerosis, was obtained using multidetector-row computed tomography. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Diabetic patients had higher log(CACS + 1) (p = 0.0089), baPWV (p = 0.0293), frequency of elevated urinary albumin excretion (UAE) (p < 0.0001) and TNF-α (p = 0.0029) and similar estimated glomerular filtration rate (eGFR) compared to nondiabetic subjects. When diabetic patients were grouped into four subgroups with or without elevated UAE and renal insufficiency (UAE of ≥30 or <30 mg/24 h and eGFR of <60 or ≥60 ml/min per 1.73 m2), patients with micro- and macroalbuminuric renal insufficiency showed the highest log(CACS + 1) (p < 0.0001), baPWV (p = 0.0068) and TNF-α (p < 0.0001) of these groups. Log(CACS + 1) (p = 0.0008) and baPWV (p = 0.0006) positively and eGFR (p < 0.0001) negatively correlated with TNF-α in diabetic patients. We find that coronary artery calcification, arterial stiffness, and renal insufficiency associate with circulating levels of TNF-α in type 2 diabetic patients.