K Nakano

Kyoto Prefectural University of Medicine, Kioto, Kyōto, Japan

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Publications (79)228.84 Total impact

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    ABSTRACT: Recent studies have suggested that variability in the systolic blood pressure (SBP) is a risk factor for cardiovascular disease (CVD). The aim of this study was to investigate the relationship between variability in the SBP and the progression of coronary artery calcification (CAC), which is a useful marker for CVD. We measured SBP in 164 consecutive patients at every visit over the course of a year and calculated the coefficient of variation and s.d. of the SBP. We performed a follow-up study using multislice computed tomography to assess the progression of the CAC score, the mean interval of which was 3.93±1.36 years. We then evaluated the relationship between variability in the SBP and progression of the CAC score. The coefficient of variation for the SBP correlated positively with the progression of the CAC score (r=0.4382, P<0.0001). Multiple regression analysis demonstrated that the coefficient of variation of the SBP (β=0.3826, P<0.0001) was independently associated with the progression of the CAC score. The visit-to-visit variability in SBP could be a novel risk factor for the progression of CAC.Hypertension Research advance online publication, 4 July 2013; doi:10.1038/hr.2013.66.
    Hypertension Research 07/2013; · 2.79 Impact Factor
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    ABSTRACT: Objective Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes. Materials and Methods We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria Results During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations ( Hazard ratio, 5.76; 95% CI, 1.65 to 24.93). Conclusions Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.
    Metabolism: clinical and experimental 01/2013; · 3.10 Impact Factor
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    ABSTRACT: Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log(CAC+1), respectively. Positive correlations were found between log(CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log(CAC+1) and eGFR (r=-0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (β=0.314, P<0.0001), sex (β=0.124, P<0.0001), hypertension (β=0.084, P=0.0008), DM (β=0.108, P<0.0001), eGFR (β=-0.079, P=0.0021) and eosinophil count (β=0.147, P<0.0001) were independent determinants of log(CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD.
    Hypertension Research 11/2011; 35(3):325-8. · 2.79 Impact Factor
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    ABSTRACT: Early detection of atherosclerosis is important for patients with type 2 diabetes mellitus because cardiovascular disease (CVD) is a main cause of death in these people. In this study, we investigated the relationship between an arterial stiffness parameter called cardio-ankle vascular index (CAVI) and coronary artery calcification (CAC). We performed a cross-sectional study in 371 type 2 diabetic patients with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAVI and CAC score determined by multislice computed tomography as well as major cardiovascular risk factors, including age, body mass index, hemoglobinA1c and the Framingham CHD risk score. CAVI was correlated with age (r = 0.301, p < 0.0001), uric acid (r = 0.236, p < 0.0001), estimated glomerular filtration rate (r = -0.145, p = 0.0166), CHD risk score (r = 0.327, p < 0.0001) and log (CAC + 1) (r = 0.303, p < 0.0001). The area under the receiver operating characteristic curve for CAVI was higher than that of CHD risk score in predicting CAC >0, CAC >100, CAC >400, or CAC >1000. CAVI is positively correlated with CAC, and is considered to be a useful method to detect CAC.
    Heart and Vessels 04/2011; 27(2):160-5. · 2.13 Impact Factor
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    ABSTRACT: Although drug-eluting stents (DES) are rapidly replacing bare metal stents, there are increasing concerns regarding the potential for very late stent thrombosis after DES implantation. It is suggested that incomplete stent apposition (ISA) due to positive remodeling is strongly associated with this. We present a case of a 68-year-old male who developed very late stent thrombosis (VLST) 40 months after DES implantation. The ISA of the stented vessel had already been detected by multislice computed tomography (MSCT). MSCT could be a useful modality to detect VLST.
    Journal of Cardiology Cases 01/2011; 3(1).
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    ABSTRACT: Recent studies have demonstrated that hyperinsulinemia is a risk factor for cardiovascular disease. The aim of this study was to evaluate the relationship between serum insulin level and the cardio-ankle vascular index (CAVI), which was developed as a marker of arterial stiffness. We performed a cross-sectional study of 260 consecutive and nondiabetic subjects with clinical suspicion of coronary heart disease. We measured CAVI in all subjects. A standard 75-g oral glucose tolerance test was performed, and plasma glucose and serum insulin levels were measured in venous blood collected at 0, 30, 60 and 120 min after the test. Statistical analyses were conducted for four subgroups according to the insulin area under the concentration time curve (InsAUC). Mean CAVI and InsAUC were 8.7 and 109.5 μIUml(-1)h(-1), respectively. Unadjusted analysis demonstrated that the InsAUC quartiles were significantly associated with CAVI (P<0.0001), and the lowest InsAUC quartile (P=0.001) had a lower glucose AUC. Analysis of covariance demonstrated that the lowest InsAUC quartile had the highest CAVI, and, after adjusting for several coronary risk factors, the highest InsAUC quartile had a higher CAVI than the second and third InsAUC quartiles (P<0.0001). In conclusion, the lowest InsAUC quartile was related to CAVI, although the lowest InsAUC quartile maintained glucose homeostasis in this study population. Both hyperinsulinemia and low insulin level are independently associated with CAVI.
    Hypertension Research 12/2010; 34(3):336-40. · 2.79 Impact Factor
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    ABSTRACT: Recent studies have suggested that hyperinsulinemia is associated with high cardiovascular risk. The purpose of this study was to assess the relationship between the serum insulin level and coronary artery calcification (CAC). We performed a cross-sectional study of 582 consecutive and nondiabetic participants with clinical suspicion of coronary heart disease, and assessed the CAC score determined by multislice computed tomography. A standard 75-g oral glucose tolerance test was performed and venous blood was collected at 0, 30, 60 and 120 min for the measurement of plasma glucose and serum insulin. Statistical analyses were conducted for 4 subgroups according to fasting insulin and insulin area under the concentration time curve (InsAUC). Mean log (CAC+1) and InsAUC were 1.6 and 109.1 µIU/mL, respectively. Unadjusted analysis demonstrated that the fasting insulin quartiles (p=0.0256) and InsAUC quartiles (p<0.0001) were significantly associated with log (CAC+1), and the lowest fasting insulin quartiles (p<0.0001) and the lowest InsAUC quartile (p=0.0006) had lower glucose AUC. Analysis of covariance demonstrated that the lowest InsAUC quartile had the highest log (CAC+1), and the highest InsAUC quartile had a higher log (CAC+1) than the second and third InsAUC quartiles, adjusted for several coronary risk factors (p<0.0001). The lowest InsAUC quartile was related to CAC, although the lowest InsAUC quartile maintained glucose homeostasis, in this study population. Not only hyperinsulinemia but also a low insulin level are independently associated with CAC.
    Journal of atherosclerosis and thrombosis 10/2010; 17(10):1033-40. · 2.93 Impact Factor
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    ABSTRACT: Pioglitazone is an insulin-sensitizing agent that has been reported to have anti-arteriosclerotic effects. The aim of this study was to obtain a better understanding of the mechanism involved in the insulin sensitizing effect of pioglitazone. A total of 50 newly diagnosed patients with type 2 diabetes were enrolled in this study and divided into two groups, 25 of who were treated with 15 mg/day pioglitazone and 25 with 500 mg/day metformin for 12 weeks. Changes in various parameters of insulin resistance including lipoprotein subclass according to particle size determined by high performance liquid chromatography, as well as glucose metabolism, were monitored to determine the relationship between lipoprotein subclass and other insulin resistance parameters. Both pioglitazone and metformin treatment were associated with significant reductions in hyperglycemia, HOMA-IR and HbA1c levels. Pioglitazone treatment, but not metformin treatment resulted in significant reductions in serum large very low-density lipoprotein (VLDL: 44.5-64.0 nm) and increases in serum adiponectin levels (both <0.001). In the pioglitazone group, the change in large VLDL levels correlated positively with changes in HbA1c (r=0.468, P=0.0174), HOMA-IR (r=0.593, P=0.0014), very small LDL (r=0.714, P<0.0001) and net electronegative charged modified-LDL (r=0.412, P=0.0399), and inversely with changes in adiponectin level (r=-0.526, P=0.0061). The results in this study suggest that the hypoglycemic effect of pioglitazone is achieved mainly through improvement of hepatic insulin resistance, and that pioglitazone may have an antiatherosclerotic effect by decreasing serum atherogenic modified-LDL and by increasing adiponectin.
    Endocrine Journal 02/2010; 57(5):423-30. · 2.23 Impact Factor
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    ABSTRACT: It has been reported that polymorphisms of human leukocyte antigen (HLA) genes and several cytokine genes are associated with an increased risk of developing gastric cancer (GC). However, the results of studies from different geographic regions, ethnic groups and study groups are inconsistent. The aim of this study was to evaluate the influence of H. pylori infection and host genetic factors on GC susceptibility in Japanese patients with GC. We analyzed genotypes for HLA class I and II, tumor necrosis factor alpha, interleukin (IL)-1beta, IL-1 receptor, IL-4, IL-4Ralpha and IL-10 in 330 H. pylori-infected noncardia patients with GC and 190 H. pylori-infected nonulcer dyspeptic controls. Haplotype analyses indicated that the frequencies of the HLA DRB1*0405 and DQB1*0401 alleles were increased in the patients with intestinal-type GC when compared with controls (both DRB1*0405 and DQB1*0401: p = 0.015, OR = 1.57, 95% CI = 1.09-2.26), but the changes were not statistically significant after correction for multiple comparisons. None of the cytokine gene polymorphisms were associated with GC susceptibility, whether patients with GC were analyzed as a group according to the histological subtype. Of interest was the comparison of controls and patients with intestinal-type GC. The frequency of an IL-10-592AA homozygote showing concomitant carriage of the HLA DRB1*0405-DQB1*0401 haplotype was significantly higher in patients with intestinal-type GC (chi(2) = 6.369, p = 0.0116, p(c) = 0.0464, OR = 2.43, 95% CI = 1.21-4.48). Our results suggest that the HLA class II and IL-10-592A/C polymorphisms synergistically affect the susceptibility to GC development of H. pylori-infected individuals in the Japanese population.
    International Journal of Cancer 07/2009; 125(11):2595-602. · 6.20 Impact Factor
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    ABSTRACT: Bilirubin is a potent antioxidant and previous studies have reported the relationship between low serum bilirubin concentration and atherosclerosis. The purpose of this study was to assess the correlation between serum bilirubin concentration and coronary artery calcification (CAC). This study consisted of 637 participants and we evaluated the relationship between CAC score determined by multislice computed tomography and serum bilirubin concentration. An inverse correlation was found between serum bilirubin concentration and log(CAC+1) (r=-0.361, P<0.0001). Multiple regression analysis also demonstrated that age (beta=0.261, P=0.0125), systolic blood pressure (beta=0.153, P=0.0237), uric acid (beta=0.126, P=0.0441), estimated glomerular filtration rate (beta=-0.139, P=0.0416) and serum bilirubin concentration (beta=-0.281, P<0.0001) were independent determinants of log(CAC+1). An increment of 1 micromol/L in serum bilirubin concentration was associated with 14% decrease in the odds for CAC score > or =400 after adjustment for several risk factors. Both age and SBP were also positively associated with CAC score > or =400, but the odds ratio for CAC score > or =400 was greater for every 1 micromol/L increment in serum bilirubin concentration than for every 1-year increment in age and 1-mmHg increment in SBP. Low serum bilirubin concentration is associated with coronary artery calcification. Serum bilirubin concentration can be measured easily in the clinical laboratory and applied in medical practice, and low serum bilirubin concentration would be useful as a provisional new risk factor of CAC.
    Atherosclerosis 02/2009; 206(1):287-91. · 3.71 Impact Factor
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    ABSTRACT: Multislice computed tomography (MSCT) permits reliable imaging of not only the coronary artery lumen but also vessel wall. It is assumed that both lipid-rich plaques and those that display positive remodeling are more prone to rupture and erosion with subsequent coronary events. The purpose of this study was to assess the correlation between the characteristics of coronary arteries by MSCT and several measures of coronary heart disease (CHD) risk. This study consisted of 424 consecutive participants who received MSCT and coronary angiography (CAG). We assessed coronary artery findings including coronary artery calcification (CAC), degree of remodeling and narrowing of lumen and characteristics including uric acid (UA) and high-sensitivity C-reactive protein (hs-CRP). Statistical analyses were conducted for four subgroups classified by the presence of significant stenosis and positive remodeling. Hs-CRP was 2.10+/-2.70mg/L in positive remodeling (+) and stenosis (+) group (PS), 1.05+/-0.97mg/L in positive remodeling (-) and stenosis (+) group (nPS), 0.94+/-0.88mg/L in positive remodeling (+) and stenosis (-) group (PnS) and 0.44+/-0.49mg/L in positive remodeling (-) and stenosis (-) group (nPnS). The results of logistic regression analysis showed that hs-CRP was higher in PS compared with the other groups (p<0.001) and higher in nPS and PnS compared with nPnS (p<0.05). Regardless of significant stenosis, positive remodeling by MSCT correlates to the increase of hs-CRP.
    Atherosclerosis 07/2008; 203(2):436-41. · 3.71 Impact Factor
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    ABSTRACT: Multislice computed tomography (MSCT) permits direct visualization of not only coronary artery stenosis but also the characteristics of plaques in patients with coronary artery disease (CAD). Also, because of its potential to be a novel risk factor for cardiovascular disease, interest in non-alcoholic fatty liver disease (NAFLD) is increasing. Participants comprised 298 consecutive patients who received MSCT to diagnose CAD. Patients with an alcohol intake exceeding 20 g/day or with a history of known liver disease were excluded from the study. Liver steatosis and 4 coronary artery findings, including remodeling lesions, lipid core plaques, calcified plaques and narrowing of lumen, were assessed. Liver steatosis was evaluated by computed tomography density of the liver and spleen. In the study, NAFLD was defined as having a liver and spleen (L:S) ratio of <1.1. The L:S ratios of patients with remodeling lesions or lipid core plaques were significantly lower than those without. NAFLD was related significantly to those findings, but there was no correlation between calcified plaques, narrowing of lumen and L:S ratios. Adjusted odds ratio of NAFLD for remodeling lesions was 2.41 (95% confidence interval (CI), 1.24-4.67; p=0.009), and those for lipid core lesions was 2.29 (95% CI, 1.15-4.56; p=0.018). NAFLD is a novel risk factor for vulnerable plaques.
    Circulation Journal 05/2008; 72(4):618-25. · 3.58 Impact Factor
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    ABSTRACT: Several epidemiological studies have shown that postprandial hyperglycemia is associated with an increased risk of cardiovascular disease (CVD). The present study was conducted in order to compare the effects of acarbose and glimepiride treatment on serum lipoprotein profiles in patients with type 2 diabetes. A total of 37 patients with newly diagnosed type 2 diabetes were studied. The patients were assigned randomly to treatment for 12 weeks with either acarbose (n=13, 100 mg x 3/day, group A), glimepiride (n=13, 2 mg/day, group G) or diet only (n=11, group D). Lipid and lipoprotein profiles before and after each treatment were evaluated. A significant reduction in the net electronegative charge of low-density lipoprotein (emLDL) was observed in group A (-1.8, P<0.01), whereas no significant change in emLDL was observed in groups G and D. In group A, small VLDL and very small LDL levels were also decreased significantly (P<0.05). The change in emLDL levels correlated significantly with changes in very small LDL (r=0.751, P<0.01) and oxidized LDL levels (r=0.623, P<0.05). These results suggest that measurement of serum emLDL may be a sensitive and clinically useful marker for determining qualitative lipoprotein abnormalities in diabetes, and that acarbose treatment lowers CVD risk by decreasing production of emLDL.
    Clinica Chimica Acta 05/2008; 390(1-2):110-4. · 2.85 Impact Factor
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    ABSTRACT: Oxidative stress is recognized widely as being associated with various disorders including diabetes, hypertension, and atherosclerosis. It is well established that hydrogen has a reducing action. We therefore investigated the effects of hydrogen-rich water intake on lipid and glucose metabolism in patients with either type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). We performed a randomized, double-blind, placebo-controlled, crossover study in 30 patients with T2DM controlled by diet and exercise therapy and 6 patients with IGT. The patients consumed either 900 mL/d of hydrogen-rich pure water or 900 mL of placebo pure water for 8 weeks, with a 12-week washout period. Several biomarkers of oxidative stress, insulin resistance, and glucose metabolism, assessed by an oral glucose tolerance test, were evaluated at baseline and at 8 weeks. Intake of hydrogen-rich water was associated with significant decreases in the levels of modified low-density lipoprotein (LDL) cholesterol (ie, modifications that increase the net negative charge of LDL), small dense LDL, and urinary 8-isoprostanes by 15.5% (P < .01), 5.7% (P < .05), and 6.6% (P < .05), respectively. Hydrogen-rich water intake was also associated with a trend of decreased serum concentrations of oxidized LDL and free fatty acids, and increased plasma levels of adiponectin and extracellular-superoxide dismutase. In 4 of 6 patients with IGT, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance.
    Nutrition research (New York, N.Y.) 03/2008; 28(3):137-43. · 1.20 Impact Factor
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    ABSTRACT: We investigated killer cell immunoglobulin-like receptor (KIR) genotypes in 92 patients with young-onset type 1 diabetes mellitus (YT1DM: < or =35 years old), 112 patients with adult-onset type 1 diabetes mellitus (AT1DM: >35 years old) and 240 control subjects. There were no differences in the frequency of KIR genotypes between controls and all the patients with T1DM or patients grouped according to age at onset of the disorder. However, when the subjects were classified into three groups according to combinations of the presence or absence of KIR3DS1/KIR3DL1 and its ligand human leukocyte antigen (HLA)-Bw4, or KIR2DL1 and its ligand HLA-C group 2, the genotype distribution was significantly different between the patients with AT1DM and controls [chi(2)= 5.993, 2 degrees of freedom (d.f.), P= 0.0500]. These data suggest that KIR polymorphisms may be associated with the age at onset of T1DM.
    Tissue Antigens 12/2007; 70(6):506-10. · 2.93 Impact Factor
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    ABSTRACT: Creatol (CTL) is a hydroxyl radical adduct of creatinine (Cr). The serum methylguanidine (MG) level and the MG/Cr molar ratio are reported to be biomarkers for oxidative stress. The aim of this study was to examine whether urinary excretion of CTL, another oxidative stress-related marker, is increased in patients with chronic renal failure (CRF). One hundred twenty-four non-dialyzed patients with chronic renal failure (serum Cr level, 1.3-10.0 mg/dL) were recruited from our hospitals. Urine and serum levels of CTL and MG were determined by high-performance liquid chromatography with the use of 9, 10- phenanthrenequinone as a fluorogenic reagent. The CTL/Cr and (CTL+MG)/Cr molar ratios in spot urine samples were also compared with those in 24-h urine samples. The urinary CTL/Cr and (CTL+MG)/Cr molar ratios increased with decreases in Cr clearance in patients with CRF. Correlations between serum and spot urine (CTL+MG)/Cr and between serum and spot urine CTL/Cr were quite similar to those in 24-h urine samples. CTL/Cr and (CTL+MG)/Cr molar ratios in both 24-h urine and spot urine samples appear to be useful indices of the severity of CRF.
    Renal Failure 02/2007; 29(3):279-83. · 0.94 Impact Factor
  • Circulation Journal - CIRC J. 01/2007; 72(4):618-625.
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    ABSTRACT: A 68-year-old woman was admitted to the authors' hospital for hepatic encephalopathy. Her laboratory data and computed tomography findings were not suggestive of liver cirrhosis. Superior mesenteric angiography revealed an extrahepatic portal-systemic shunt with a main cause of hepatic encephalopathy. Despite treatment with branched-chain amino acid, lactulose, and kanamycin, hyperammonemia was prolonged, and the portal-systemic shunt was therefore treated with balloon-occluded retrograde transvenous obliteration. After the procedure, hyperammonemia was improved, and there were no signs of recurrent portal-systemic encephalopathy.
    Journal of Vascular and Interventional Radiology 01/2007; 17(12):1951-5. · 2.00 Impact Factor
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    ABSTRACT: Research progress on the pleiotropic effects of interferons (IFN) has thus far required detecting responses by weak IFN signals. The activity of 2',5'-oligoadenylate synthetase (2-5OAS) is a valuable indicator in the prognosis and IFN treatment of patients with viral diseases such as hepatitis B and C. Although serum samples generally are used to measure enzyme activity, their values depend on the exact conditions under which blood is stored and the degree of haemolysis that occurs during blood drawing or serum separation. This study presents an improved method of evaluating 2-5OAS activity by using whole blood samples containing heparin, which are frozen and then thawed, instead of serum samples. This method is more reliable, convenient, and 50-100 times more sensitive than the conventional methods of measuring serum 2-5OAS activity. The reliability and sensitivity of this improved method enables detection of the effects of low doses of oral IFN administration or changes in the IFN and cytokine system by infection or autoimmune diseases.
    Journal of Virological Methods 10/2006; 136(1-2):185-92. · 1.90 Impact Factor
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    ABSTRACT: Resistin is a novel cysteine-rich protein that plays a role in the development of insulin resistance and atherosclerosis. HMG-CoA reductase inhibitors (statins) possess anti-inflammatory properties that are independent of their lipid-lowering action. The aims of this study were to investigate the effect of atorvastatin on expression of resistin in vitro and to determine the effect of 6 months of treatment with atorvastatin on serum levels of resistin in patients with type 2 diabetes. 3T3-L1 adipocytes and human monocytes/macrophages and preadipocytes were incubated with 1 and 10 micromol/l atorvastatin for 24 and 48 h, followed by measurement of resistin mRNA by the quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Serum resistin concentration in the patients with type 2 diabetes was measured at baseline and after 6 months of atorvastatin treatment (10 mg/day). qRT-PCR analysis revealed that atorvastatin decreased resistin mRNA expression in a dose- and time-dependent manner. Serum resistin concentration tended to decrease after 6 months of atorvastatin treatment, although this decrease did not reach statistical significance. In conclusion, the findings of our in vitro study contribute to the growing volume of evidence on the anti-inflammatory and anti-atherosclerotic effects of statins, and led us to suggest that statins may control inflammatory responses by inhibiting expression of resistin mRNA. It is necessary to confirm the findings of our in vitro study by an appropriately designed large-scale clinical study.
    Pharmacology 02/2006; 76(1):34-9. · 1.60 Impact Factor

Publication Stats

2k Citations
228.84 Total Impact Points

Institutions

  • 1991–2013
    • Kyoto Prefectural University of Medicine
      • • Division of Endocrinology, Diabetes and Metabolism
      • • Graduate School of Medical Science
      • • Division of Preventive Medicine
      Kioto, Kyōto, Japan
  • 2006
    • Kyoto Prefectural University
      Kioto, Kyōto, Japan
  • 2003
    • The University of Tokushima
      • Department of Clinical Neuroscience
      Tokusima, Tokushima, Japan
    • Kobe Pharmaceutical University
      Kōbe, Hyōgo, Japan