OBJECTIVE -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.RESEARCH DESIGN AND METHODS -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 Ͻ1 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.RESULTS -Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 Ϯ 62 vs. 121 Ϯ 55 pg/ml, P Ͻ 0.001; urinary IL-18 97 Ϯ 159 vs. 47 Ϯ 54 pg/ml, P ϭ 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] ϭ 0.525, P Ͻ 0.001), HbA 1c (r ϭ 0.242, P ϭ 0.029), high-sensitivity C-reactive protein (hs-CRP) (r ϭ 0.240, P ϭ 0.031), and urinary ␤-2 microglobulin (r ϭ 0.235, P ϭ 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r ϭ 0.225, P ϭ 0.042) and baPWV (r ϭ 0.232, P ϭ 0.040). We also found a significant correlation between urinary IL-18 and AER (r ϭ 0.309, P ϭ 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] ϭ 0.405, P Ͻ 0.001) and hs-CRP (B ϭ 0.207, P ϭ 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B ϭ 0.295, P ϭ 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r ϭ 0.489, P Ͻ 0.001 and r ϭ 0.320, P ϭ 0.005) and changes in AER during the follow-up period (r ϭ 0.268, P ϭ 0.018 and r ϭ 0.234, P ϭ 0.042).CONCLUSIONS -Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases. Diabetes Care 28:2890 -2895, 2005L ow-grade inflammation (microinflammation) occurs in diabetic patients as well as those with cardiovascular diseases (1,2). Several reports indicate that high-sensitivity C-reactive protein (hs-CRP) (3) and proinflammatory cytokines such as interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-␣, and IL-18 are elevated in patients with type 2 diabetes (4 -7). The mechanisms for elevation of serum IL-18 levels in type 2 diabetes remain unclear, although oxidative stress is a candidate (8). Activation of nuclear factor-B through oxidative stress induced by hyperglycemia increas...

Higher ALP level at diagnosis is one of the predictors for UDCA failure. Combination treatment of bezafibrate in addition to UDCA may be an effective treatment for PBC patients refractory to UDCA.

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The results of this cross-sectional study showed that the measurement of haemodynamic parameters was useful, together with IMT, in estimating the risk of previous cerebral infarction in Type 2 diabetic patients. The predictive value of these parameters in identifying the risk of future cerebral infarction must await the results of future prospective studies.

Elderly patients with DILI show different clinical features than younger patients with DILI. These features should be taken into account in the diagnosis and treatment of DILI in the elderly.