Nakamura Akihiko, Shikata Kenichi, Hiramatsu Makoto, Nakatou Tatsuaki, Kitamura Takuya, Wada Jun, Itoshima Tatsuya, Makino Hirofumi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Diabetes Care. 2005 Dec;28(12):2890-5. doi: 10.2337/diacare.28.12.2890.
Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes.
Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance <1 ml/s) were excluded. We assessed clinical parameters and measured serum and urinary IL-18 levels, serum IL-6 levels, carotid intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in all patients. Further, we evaluated changes of urinary albumin excretion rate (AER) after 6 months in 76 diabetic patients.
Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 +/- 62 vs. 121 +/- 55 pg/ml, P < 0.001; urinary IL-18 97 +/- 159 vs. 47 +/- 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA(1c) (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary beta-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042).
Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.
白细胞介素（IL）-18是一种由单核细胞分泌的促炎细胞因子。血清IL-18浓度是心血管疾病患者死亡的有力预测指标。最近的研究表明，微炎症参与糖尿病肾病以及心血管疾病的发病机制。本研究旨在验证以下假设：血清IL-18水平是2型糖尿病患者肾病和动脉粥样硬化的共同预测指标。
纳入82例日本2型糖尿病患者和55例年龄及性别匹配的健康对照者。排除肾功能不全（肌酐清除率<1 ml/s）的患者。我们评估了所有患者的临床参数，并测量了血清和尿IL-18水平、血清IL-6水平、颈动脉内膜中层厚度（IMT）和臂踝脉搏波速度（baPWV）。此外，我们评估了76例糖尿病患者6个月后尿白蛋白排泄率（AER）的变化。
与对照者相比，2型糖尿病患者的血清和尿IL-18水平显著升高（血清IL-18：179±62 vs. 121±55 pg/ml，P<0.001；尿IL-18：97±159 vs. 47±54 pg/ml，P = 0.035）。单变量线性回归分析显示，血清IL-18与AER（相关系数[r]=0.525，P<0.001）、糖化血红蛋白（HbA1c）（r = 0.242，P = 0.029）、高敏C反应蛋白（hs-CRP）（r = 0.240，P = 0.031）和尿β2微球蛋白（r = 0.235，P = 0.036）之间存在显著正相关。血清IL-18水平也与颈动脉IMT（r = 0.225，P = 0.042）和baPWV（r = 0.232，P = 0.040）呈正相关。我们还发现尿IL-18与AER之间存在显著相关性（r = 0.309，P = 0.005）。多变量线性回归分析显示，AER（标准相关系数[B]=0.405，P<0.001）和hs-CRP（B = 0.207，P = 0.033）与血清IL-18水平独立相关。AER也与尿IL-18水平独立相关（B = 0.295，P = 0.005）。此外，血清和尿IL-18水平与6个月后的AER呈正相关（r = 0.489，P<0.001和r = 0.320，P = 0.005）以及随访期间AER的变化（r = 0.268，P = 0.018和r = 0.234，P = 0.042）。
血清IL-18水平可能是糖尿病肾病以及心血管疾病进展的预测指标。
