Elevated soluble intercellular adhesion molecule-1 levels in patients with systemic lupus erythematosus: relation to insulin resistance

OBJECTIVE: Intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin supergene family and play a central role in cell-to-cell and in cell-to-extracellular matrix-mediated immune responses. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide variety of immunological abnormalities. The relationship between soluble adhesion molecules and insulin resistance has been observed in different populations. However, the association of circulating levels of soluble cell adhesion molecules with insulin resistance and/or hyperinsulinemia in patients with SLE has not been extensively established. METHODS: We evaluated the relationship of soluble ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) to insulin resistance in 68 patients with SLE and 34 age-matched healthy controls. RESULTS: Patients with SLE had significantly higher fasting insulin levels, homeostasis model assessment insulin resistance (HOMA-IR), HOMA beta-cell, and plasma levels of sICAM-1 and sVCAM-1 than controls. SLE patients with HOMA-IR in the top quartile had the highest plasma levels of sICAM-1. However, there was no statistical difference in plasma levels of sVCAM-1 between patients in the respective quartiles of insulin sensitivity-related variables. Plasma levels of sICAM-1, but not sVCAM-1, were significantly correlated with fasting insulin (r = 0.327, p = 0.006), HOMA-IR (r = 0.278, p = 0.022), and HOMA beta-cell (r = 0.359, p = 0.003). In addition, fasting insulin was responsible for sICAM-1 variability in patients with SLE. CONCLUSION: The elevation of plasma levels of sICAM-1 was associated with a status of insulin resistance in patients with SLE.     

Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes

OBJECTIVE: To investigate the relationship of inflammation and endothelial activation with insulin resistance and adiposity in type 2 diabetes. METHODS AND RESULTS: Hundred and thirty-four (45 female) type 2 diabetic subjects aged 50-75 in the Fenofibrate Intervention and Event Lowering in Diabetes Study in Helsinki were examined before fenofibrate intervention. Fasting levels of circulating intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) (vascular cell adhesion molecule), ultra-sensitive C-reactive protein (CRP), human serum amyloid A (hSAA), interleukin-6 (IL-6), macrophage colony-stimulating factor (M-CSF), secretory phospholipase A(2) IIA (PLA(2)), total, HDL and LDL cholesterol, triglycerides, P-glucose, HbA1c, and serum free insulin were determined. Insulin resistance was assessed by the homeostasis model. HOMA IR correlated significantly with all measures of adiposity and markers of inflammation and endothelial dysfunction. BMI was significantly associated with inflammation and endothelial activation, but with neither lipoproteins nor glycaemic control. After controlling for age, gender and BMI, HbA1c correlated significantly with CRP, hSAA, ICAM-1, E-selectin, and HOMA IR. HDL cholesterol correlated inversely with IL-6, M-CSF, E-selectin, and HOMA IR. HbA1c, phospholipase A(2), VCAM-1, and HDL cholesterol remained independent determinants of HOMA IR in the linear regression analysis controlled for age, gender, and BMI. CONCLUSION: Endothelial activation and acute-phase reaction correlate with insulin resistance and obesity in type 2 diabetic patients.     

Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels

As men age, serum testosterone levels decrease, a factor that may contribute to some aspects of age-related physiological deterioration. Although androgen replacement has been shown to have beneficial effects in frankly hypogonadal men, its use in elderly men with borderline hypogonadism is controversial. Furthermore, current testosterone replacement methods have important limitations. We investigated the ability of the orally administered aromatase inhibitor, anastrozole, to increase endogenous testosterone production in 37 elderly men (aged 62-74 yr) with screening serum testosterone levels less than 350 ng/dl. Subjects were randomized in a double-blind fashion to the following 12-wk oral regimens: group 1: anastrozole 1 mg daily (n = 12); group 2: anastrozole 1 mg twice weekly (n = 11); and group 3: placebo daily (n = 14). Hormone levels, quality of life (MOS Short-Form Health Survey), sexual function (International Index of Erectile Function), benign prostate hyperplasia severity (American Urological Association Symptom Index Score), prostate-specific antigen, and measures of safety were compared among groups. Mean +/- SD bioavailable testosterone increased from 99 +/- 31 to 207 +/- 65 ng/dl in group 1 and from 115 +/- 37 to 178 +/- 55 ng/dl in group 2 (P < 0.001 vs. placebo for both groups and P = 0.054 group 1 vs. group 2). Total testosterone levels increased from 343 +/- 61 to 572 +/- 139 ng/dl in group 1 and from 397 +/- 106 to 520 +/- 91 ng/dl in group 2 (P < 0.001 vs. placebo for both groups and P = 0.012 group 1 vs. group 2). Serum estradiol levels decreased from 26 +/- 8 to 17 +/- 6 pg/ml in group 1 and from 27 +/- 8 to 17 +/- 5 pg/ml in group 2 (P < 0.001 vs. placebo for both groups and P = NS group 1 vs. group 2). Serum LH levels increased from 5.1 +/- 4.8 to 7.9 +/- 6.5 U/liter and from 4.1 +/- 1.6 to 7.2 +/- 2.8 U/liter in groups 1 and 2, respectively (P = 0.007 group 1 vs. placebo, P = 0.003 group 2 vs. placebo, and P = NS group 1 vs. group 2). Scores for hematocrit, MOS Short-Form Health Survey, International Index of Erectile Function, and American Urological Association Symptom Index Score did not change. Serum prostate-specific antigen levels increased in group 2 only (1.7 +/- 1.0 to 2.2 +/- 1.5 ng/ml, P = 0.031, compared with placebo). These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Serum estradiol levels decrease modestly but remain within the normal male range. The physiological consequences of these changes remain to be determined.     

Relation of C-reactive protein to oxidative stress and to endothelial activation in essential hypertension

BACKGROUND: C-reactive protein (CRP) predicts cardiovascular outcome. Oxidative stress is considered to be involved in endothelial alteration. We hypothesized that in essential hypertension (EH), oxidative stress, as measured by 8-iso-prostaglandin-F(2alpha) (8-iso-PGF(2alpha)), should be associated with increased CRP and endothelial activation, as evaluated by soluble intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) plasma levels. METHODS: In 83 subjects with mild EH and in 50 healthy control subjects we measured, in basal conditions, plasma levels of hs-CRP, 8-iso-PGF(2alpha), ICAM-1 and VCAM-1, and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Subjects with EH had higher levels of 8-iso-PGF(2alpha) (P < .0001), CRP (P < .001), ICAM-1 and VCAM-1 (P < .001), and TNF-alpha (P < .001) than did control subjects. We divided successively EH according to CRP values (<1, 1-3, >3 mg/L), and we observed increasing and significantly different levels of the endothelial parameters and of TNF-alpha along with increasing CRP. Linear analysis of correlation pointed out significant correlation of CRP with 8-iso-PGF(2alpha) (r = 0.730, P < .001), ICAM-1 and VCAM-1 (r = 0.642 and 0.468, P < .001 respectively), and TNF-alpha (r = 0.609, P < .001). Multiple regression analysis using CRP as a dependent variable confirmed the relationship of CRP with systolic blood pressure (beta 0.216, P = 0.039) and with 8-iso-PGF(2alpha) (beta 0.602, P = .0001). CONCLUSIONS: Our data demonstrate that in EH, inflammatory molecules such as CRP and TNF-alpha are increased and related to both oxidative stress and endothelial activation.     

Circulating adhesion molecules and severity of coronary atherosclerosis

BACKGROUND: Circulating leukocytes are recruited at atherosclerotic sites through a family of adhesion molecules. Circulating forms of adhesion molecules in peripheral blood can be quantified now. OBJECTIVE: To evaluate the relationship between circulating adhesion molecules and severity of coronary atherosclerosis. METHODS: Subjects included 81 patients undergoing diagnostic coronary angiography, 12 of whom had normal coronary arteries (control group). The remaining 69 patients with demonstrable coronary atherosclerosis were divided into two groups by use of Gensini scores, namely mild atherosclerosis (n = 36, Gensini score 1-20) and severe atherosclerosis (n = 33, Gensini score > 20). Serum levels of circulating intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin of groups measured before angiography were compared. RESULTS: Circulating levels of ICAM-1 in members of mild and severe atherosclerosis groups were significantly higher than those in members of the control group, whereas there was no significant difference among circulating levels of VCAM-1 in members of the three groups. Circulating levels of E-selectin in members of the mild atherosclerosis group were significantly higher than those in members of the severe atherosclerosis and control groups. CONCLUSIONS: These findings suggest that E-selectin is related to the early stage, and ICAM-1 is related to the advanced stage, of coronary atherosclerosis. With progression of atherosclerosis, one-step adhesion by ICAM-1 could become more important than multistep adhesion involving E-selectin, ICAM-1, and VCAM-1. These molecules may serve as markers for severity of coronary atherosclerosis.     

Gliclazide treatment lowers serum ICAM-1 levels in poorly controlled type 2 diabetic patients

OBJECTIVE: To investigate the potential effect of gliclazide on serum ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) levels in poorly controlled type 2 diabetic patients. PATIENTS AND METHODS: The study included 104 patients, randomly divided into two groups. Group A comprised 53 patients (26 men) treated with gliclazide with a mean age of 67.5+/-9.9 years, a mean diabetes duration of 13.4+/-5.4 years and a mean HbA1c of 8.6+/-1.1%. Group B comprised 51 patients (25 men) treated with glibenclamide with a mean age of 66.4+/-10.9 years, a mean diabetes duration of 13.2+/-6.1 years and a mean HbA1c of 8.4+/-1.3%. A third group of 30 healthy controls (15 men) with a mean age of 63.3+/-10.4 years was also included. Serum levels of ICAM-1 and VCAM-1 were measured at the beginning of the study and after six months of treatment. RESULTS: Pretreatment serum ICAM-1 and VCAM-1 levels did not differ between groups A and B, while they were significantly higher (P=0.0001) than in healthy controls. No significant difference in HbA1c, body mass index, blood pressure control and lipid profile between the two groups was observed after the sixth month of treatment. In group A, serum ICAM-1 levels after six months of treatment were significantly reduced from 623.12+/-61.17 ng/ml to 370.14+/-49.92 ng/ml (P=0,01), while no reduction was found in VCAM-1 levels. In group B, no reduction was found in serum ICAM-1 and VCAM-1 levels after the end of the study. CONCLUSIONS: Our results suggest that gliclazide treatment reduces serum ICAM-1 levels in poorly controlled type 2 diabetic patients. This reduction is independent of the hypoglycaemic action of gliclazide.     

Effect of a diet and exercise intervention on oxidative stress, inflammation and monocyte adhesion in diabetic men

Diabetes increases the risk of coronary artery disease. We examined the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation and cell adhesion. Diabetic men (N=13) were placed on a high-fiber, low-fat diet in a 3-week residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and post-intervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin, oxidative stress marker 8-isoprostaglandin F2alpha (8-iso-PGF2alpha), the inflammatory protein C-reactive protein (CRP), and soluble intracellular adhesion molecule (sICAM)-1 and sE-selectin as indicators of endothelial activation. Using subject sera and human aortic endothelial cell (HAEC) culture systems, serum-induced monocyte adhesion, ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and cell surface abundance, and monocyte chemotactic protein-1 (MCP-1) production were determined. Nitric oxide (NO), superoxide, and hydrogen peroxide production were measured in vitro by fluorometric detection. After 3 weeks, significant reductions (p<0.05) in BMI, all serum lipids including total cholesterol (pre: 188.9+/-10.1 mg/dL versus post: 146.3+/-3.8 mg/dL) and low-density lipoprotein (103.1+/-10.2 mg/dL versus 76.4+/-4.3 mg/dL), fasting serum glucose (157.5+/-10.1 mg/dL versus 126.7+/-8.7 mg/dL), insulin (33.8+/-4.0 microU/ml versus 23.8+/-3.4 microU/ml), homeostasis model assessment for insulin resistance, 8-iso-PGF2alpha, CRP, sICAM-1, and sE-selectin were noted. In vitro, serum-stimulated monocyte adhesion, cellular ICAM-1 and VCAM-1 expression (p<0.05), and fluorometric detection of superoxide and hydrogen peroxide production decreased, while a concomitant increase in NO production was noted (all p<0.01). A combination of diet and exercise ameliorates oxidative stress, inflammation, and monocyte-endothelial interaction. Intensive lifestyle modification may improve novel CAD risk factors in men with diabetes.     

Assessment of hypogonadism and its determinants among adult men with type 2 diabetes mellitus

Background and aimsThe impact of utilizing both symptoms as well as biochemically confirmed androgen deficiency in diagnosis of hypogonadism among type 2 diabetic men is relatively less studied. Furthermore, various determinants of hypogonadism in these men especially the role of insulin resistance and hypogonadism were studied.MethodsThis is a cross sectional study of 353 T2DM men aged 20–70 years of age. Hypogonadism was defined by taking both symptoms as well as calculated testosterone levels. Symptoms were defined using androgen deficiency in ageing male (ADAM) criteria. Various metabolic and clinical parameters were assessed and evaluated with regards to presence or absence of hypogonadism.ResultsAmong 353 patients, 60 had both symptoms as well as biochemical evidence of hypogonadism. Assessment of calculated free testosterone but not total testosterone identified all such patients. Body mass index, HbA1c, fasting triglyceride level and HOMA IR inversely correlated with calculated free testosterone. We found that insulin resistance (HOMA IR) was independently associated with hypogonadism (odds ratio=1.108).ConclusionAssessment of both symptoms of hypogonadism and calculated free testosterone represents a better way for correct identification of hypogonadal diabetic men. Insulin resistance has a strong association with hypogonadism independent of obesity and complication status of diabetes.     

Pioglitazone produces rapid and persistent reduction of vascular inflammation in patients with hypertension and type 2 diabetes mellitus who are receiving angiotensin II receptor blockers

Inhibition of the renin-angiotensin system reportedly exerts potent antiatherogenic effects by reducing vascular inflammation. We tested the hypothesis that pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, further reduces vascular inflammation in patients receiving angiotensin II receptor blockers. Patients with hypertension who had developed type 2 diabetes mellitus were randomly assigned to receive either pioglitazone (15 mg/d, n = 20) or voglibose, an alpha-glucosidase inhibitor (0.6 mg/d, n=19) for 6 months, and changes in their serum concentrations of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were monitored. Pioglitazone, but not voglibose, reduced CRP levels within 1 month (-51%+/-7%, mean+/-SEM; P<.001). C-reactive protein levels were decreased after 6 months of treatment with either pioglitazone or voglibose, with the former being more effective (-57%+/-8% vs -9%+/-18%; P<.05). The levels of ICAM-1 and VCAM-1 were significantly reduced after 1 month of pioglitazone therapy (-9%+/-3% and -8%+/-3%, respectively; both P<.05), with the beneficial effects persisting throughout the study period. In contrast, the levels of ICAM-1 and VCAM-1 were not altered during the study period in patients on voglibose. There was no correlation between the reduction of hemoglobin A1c and that of CRP, ICAM-1, or VCAM-1. These results suggest that augmentation with pioglitazone further reduces vascular inflammation in patients with hypertension and diabetes who are receiving angiotensin II receptor blockers. This may contribute to the reduction of cardiovascular events in this at-risk population.     

Circulating intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in patients with type 2 diabetes mellitus

Serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in patients with type 2 diabetes mellitus (n = 64) and control subjects (n = 40) were studied. Serum ICAM-1 concentrations in diabetic patients were significantly higher than those of control subjects (378.2 +/- 70.0 versus 220.4 +/- 31.8 ng/ml, P < 0.01). By multiple regression analysis, hemoglobin A1c was independently associated with serum ICAM-1 concentration in patients with diabetes. The serum VCAM-1 concentration of diabetic patients with macroangiopathy was higher than those of patients without macroangiopathy and of control subjects (806.9 + 276.5 versus 639.0 +/- 146.0 (P < 0.01), and 652.1 +/- 146.9 ng/ml (P < 0.01), respectively). There was no difference in serum E-selectin concentration between diabetic patients with or without macroangiopathy and normal control subjects. These results suggest that adhesion molecules may contribute to the development of atherosclerosis in the diabetic state.     

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.     

Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy.

AIMS: To clarify the correlation between serum concentrations of soluble adhesion molecules and diabetic microangiopathy or macroangiopathy in patients with Type 2 diabetes. METHODS: Patients with diabetic retinopathy and intima-media thickness of common carotid artery (CCA-IMT) < 1.1 mm were classified as the microangiopathy group (n = 62). Patients with CCA-IMT > or = 1.1 mm and without retinopathy were classified as the macroangiopathy group (n = 95). Patients with CCA-IMT < 0.9 mm and without retinopathy were assigned to the no complications group (n = 139). Clinical characteristics and soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin levels were compared between the groups. RESULTS: Patients with microangiopathy had a significantly longer duration of diabetes, were hypertensive and more likely to have a positive family history of diabetes than the control group. Patients with macroangiopathy were more likely to be smokers, hypertensive, and have a family history of hypertension. Soluble ICAM-1, VCAM-1, and E-selectin levels were significantly higher in the microangiopathy group than in the control group. Soluble VCAM-1 and E-selectin levels, but not ICAM-1 levels, were significantly elevated in the macroangiopathy group. These results were unchanged after adjustment for age, sex, duration of diabetes, blood pressure, HbA1c, HDL-cholesterol, and smoking status. CONCLUSIONS: Our results suggest that soluble adhesion molecules are related to both diabetic micro- and macroangiopathy. The relative contributions of adhesion molecules may be greater in the former than latter patients with Type 2 diabetes.     

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study

The Epidemiological Study of Myocardial Infarction Study which enrolled 9758 apparently healthy men aged 50-59 years, is a prospective cohort study designed to evaluate markers of coronary risk. Soluble forms of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured in plasma obtained at baseline from 317 subjects who suffered a coronary event during the 5-year follow-up and in twice the number of control subjects who were matched for center, age and day of inclusion in a nested case-control design. The relative risk associated with the highest compared with the lowest thirds of ICAM-1 (>625 versus <502 ng/ml) was 2.45 (95% CI: 1.64-3.65, P<0.001) without adjustment; it decreased moderately (RR: 2.09; 95% CI: 1.34-3.24, P<0.001) after control for lipid and non-lipid factors and remained significantly elevated after adjustment for C-reactive protein (CRP) (RR: 1.90; 95% CI: 1.21-2.96, P=0.005). Plasma ICAM-1 was essentially associated with the risk of myocardial infarction or coronary death and also with angina pectoris. Subjects with CRP presented elevated coronary risk only if ICAM-1 was high. An elevated level of VCAM-1 was not associated with any risk of future acute coronary event, or with angina pectoris. This data indicates that plasma levels of ICAM-1 may serve as risk markers for future coronary events whatever their clinical presentation and that risk is better defined using simultaneous measurements of ICAM-1 and CRP than any of these levels separately.     

Up-regulation of circulating adhesion molecules in bronchiectasis.

Adhesion molecules are expressed on the surface of endothelial cells and leukocytes and are responsible for mediating the migration of intravascular leukocytes into inflamed tissue. Intensive recruitment of neutrophils into the airways occurs in bronchiectasis, although little is known about the role of adhesion molecules in this process. The authors, therefore, determined serum levels of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in stable bronchiectasis patients (n=37) and healthy control subjects (n=17), and evaluated their relationship with clinical markers of disease severity in bronchiectasis. Serum levels of E-selectin, ICAM-1 and VCAM-1 in bronchiectasis patients were significantly higher than those in control subjects (p=0.02, <0.0001 and 0.0002 respectively). Both E-selectin and ICAM-1 levels were inversely related to forced expiratory volume in one second (FEV1)% predicted (r=-0.57, p<0.001; and r=-0.53, p=0.001 respectively), and FVC% predicted (r=-0.52, p=0.002; and r=-0.46, p=0.005). This was not the case for VCAM-1 levels. There was a correlation between serum ICAM-1 levels and 24 h sputum volume (r=0.34, p= 0.04). Serum E-selectin and ICAM-1, but not VCAM-1, levels showed correlation with the number of lung lobes affected by bronchiectasis (r=0.35, p=0.04 and r=0.34, p=0.04 respectively). These original observations strongly suggest that E-selectin, intercellular adhesion molecule-1 and Vascular adhesion molecule-1 could play a significant role in the pathogenesis of bronchiectasis.     

2型糖尿病患者血清炎性因子与颈动脉粥样硬化的相关性研究

目的 研究2型塘尿病患者血清炎性因子水平与颈动脉粥样硬化的关系.方法 选择124例2型糖尿病患者,采用酶联免疫吸附法测定血清内皮细胞猫附分子1（ICAM-1）、血管细胞黏附分子1（VCAM-1）,E选择素、白细胞介素6（IL-6）和C反应蛋白（CRP）水平;按颈动脉超声检查结果将糖尿病患者分为颈动脉正常组（38例）、颈动脉增厚组（40例）和颈动脉斑块组（46例）.选择40例健康体检者作为对照组,比较各组血清炎性因子水平.结果 ①颈动脉正常组血清ICAM-1,IL-6及CRP较对照组升高,颈动脉增厚组ICAM-1、VCAM-1、IL-6及CRP水平高于颈动脉正常组,颈动脉斑块组ICAM-1、VCAM-1、E选择素高于颈动脉增厚组,上述指标各组差异均有统计学意义,P 〈0.05,或P〈0.01.②相关性分析显示,颈动脉内-中膜厚度（IMT）增厚程度与糖化血红蛋白（HbAlc）（r=0.472）、ICAM-1（r=0.501）、VCAM-1（r = 0.484）、E选择素（r＝0.289）、IL-6（r=0.425）及CRP（r=0.381）呈正相关.患者HbAlc与ICAM-1、VCAM-1、IL-6及CRP呈正相关.ICAM-1、VCAM-1、E选择素、IL-6、CRP间呈正相关,均P〈0.01或P〈0.05.结论 炎性反应参与了2型糖尿病患者颈动脉粥样硬化的发病过程,血清炎性因子水平可以在一定程度上反映糖尿病患者的颈动脉粥样硬化程度.     

Clinical significance of serum levels of E-selectin,intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients

OBJECTIVES: This study evaluated serum concentrations of soluble cell adhesion molecules in patients with gastric cancer and in healthy control subjects. Our objectives were to correlate these levels with clinicopathological features, established tumor markers, and patient survival, and to assess changes in serum levels of cell adhesion molecules after tumor surgery. METHODS: The serum concentrations of the adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were investigated by ELISA in 57 gastric cancer patients, both before and 7 days after surgery, and in 47 healthy control subjects. RESULTS: Preoperative serum concentrations of ICAM-1 and VCAM-1 in gastric cancer patients were significantly higher when compared with those of healthy controls, whereas there were no differences regarding serum E-selectin levels. Serum levels of E-selectin, ICAM-1, and VCAM-1 correlated significantly with each other. There was a significant association between preoperative levels of all three adhesion molecules and disease stage, gastric wall invasion, lymph node involvement, and presence of distant metastases. Their concentrations decreased significantly after radical resection of the tumor, whereas they remained almost unchanged in patients with unresectable disease. Elevated preoperative serum levels of E-selectin, ICAM-1, and VCAM-1 levels were found in 24.6%, 33.3%, and 28.1% of patients, respectively. Elevated levels of all three molecules were significant prognostic factors for patient survival but not independent of disease stage. CONCLUSIONS: These findings suggest that serum concentrations of E-selectin, ICAM-1, and VCAM-1 may reflect tumor progression and metastasis, and may be clinically useful.     

Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.

AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.     

Baseline ICAM-1 and VCAM-1 are increased in initially healthy middle-aged men who develop cardiovascular disease during 6.6 years of follow-up

The objective of the present study was to investigate if there was a difference in baseline serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) between groups with and without cardiovascular events during a mean follow-up of 6.6 years in a group of initially healthy 58-year-old men. A further aim was to examine if high serum concentrations of ICAM-1 and VCAM-1 were associated with carotid and femoral artery plaque occurrence, separately. Men with cardiovascular events during follow-up had higher median serum ICAM-I and VCAM-I than those without events (P < .05). The median of serum ICAM-I and VCAM-1 in the event group was used as the cutoff level, and in those with ICAM-1 and VCAM-1 above the cutoff value, there was an increased risk of having a plaque in the femoral artery (OR = 2.8, 95% CI = 1.8-4.3; and OR = 1.6, 95% CI = 1.1-2.5, respectively).     

Effect of preexisting statin use on expression of C-reactive protein, adhesion molecules, interleukin-6, and antioxidized low-density lipoprotein antibody in patients with unstable angina undergoing coronary stenting

BACKGROUND: Statins are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol lowering effect. HYPOTHESIS: We studied the effect of statins on expression of C-reactive protein (CRP), interleukin-6 (IL-6), adhesion molecules, and antioxidized low-density lipoprotein antibody (anti-oxLDL Ab) in patients with unstable angina (Braunwald class IIb or IIIb) undergoing coronary stenting. METHODS: Consecutive 50 patients with unstable angina were included in the study. We classified the study subjects as patients using statins (Group A, n=20, men 10, mean age 62 years) and patients not using statins (Group B, n=30, men 15, mean age 60 years). RESULTS: Baseline levels of inflammatory markers were similar in the two groups. However, 24 h after coronary stenting, serum levels of CRP (2.00 vs. 4.63 mg/l, p < 0.05), intercellular adhesion molecule-1 (ICAM-1) (217 vs. 261 ng/ml, p < 0.01), and anti-oxLDL Ab (8.97 vs. 12.96 U/ml, p < 0.05) were significantly higher in Group B than in Group A. Furthermore, 72 h after coronary stenting, serum levels of CRP (3.00 vs. 5.50 mg/l, p < 0.01) and ICAM-1 (222 vs. 277 ng/ml, p < 0.05) were significantly higher in Group B than in Group A. CONCLUSIONS: Preexisting statin therapy plays a role in reducing the serum levels of CRP, ICAM-1, and anti-oxLDL Ab after coronary stenting in patients with unstable angina. These data support an anti-inflammatory or plaque-stabilizing effect of statin therapy.     

Association of hypogonadism and estradiol levels with bone mineral density in elderly men from the Framingham study

BACKGROUND: Both hypogonadism and low estrogen levels adversely affect bone health in young men. In elderly men, who are at greatest risk for osteoporotic fracture, the influence of hypogonadism on bone mineral density remains unclear, as does the relative effect of estrogen status compared to hypogonadism. OBJECTIVE: To examine the relation of hypogonadism and estrogen status to bone mineral density in elderly men. DESIGN: Community-based, prospective cohort study. SETTING: Framingham, Massachusetts. PATIENTS: Male participants of the Framingham Study. MEASUREMENTS: Total testosterone, total estradiol, and luteinizing hormone were measured in participants at all four biennial examinations from 1981 to 1989. Values from at least three of four examinations were averaged. Hypogonadism was defined as a mean testosterone level less than 10.4 nmol/L (<3.0 ng/mL) or a mean luteinizing hormone level of 20 IU/L or greater. An alternate definition of hypogonadism based only on a mean testosterone level less than 10.4 nmol/L (<3.0 ng/mL) was also used. In 1988-1989, bone mineral density was measured at the proximal femur (femoral neck, Ward triangle, and trochanter) and lumbar spine by using dual-photon absorptiometry and at the radial shaft by using single-photon absorptiometry. The association of hypogonadism with bone mineral density was examined with adjustment for confounders, including estradiol levels. A similar model that adjusted for hypogonadism was used to examine the association of estradiol level (ranked as quartiles) with bone mineral density. RESULTS: Of 448 men with bone mineral density measurements, 405 had evaluable hormone levels (mean age, 75.7 years [range, 68 to 96 years]); 71 (17.5%) of the 405 men were hypogonadal. Bone mineral density at any site did not significantly differ in hypogonadal men compared with eugonadal men (for example, bone mineral density at the femoral neck was 0.89 g/cm(2) vs. 0.87 g/cm(2), respectively; P > 0.2), even when alternate definitions of hypogonadism were used. In contrast, compared with the lowest estradiol quartile, men with higher estradiol levels had greater mean bone mineral density at all sites (for example, bone mineral density at the femoral neck was 0.84 g/cm(2), 0.88 g/cm(2), 0.86 g/cm(2), and 0.91 g/cm(2) from the lowest to the highest estradiol quartile; P for trend = 0.002). The difference in mean bone mineral density between men in the lowest and those in the highest estradiol quartile levels was similar to the effect of 10 years of aging on bone mineral density. CONCLUSIONS: In elderly men, hypogonadism related to aging has little influence on bone mineral density, but serum estradiol levels have a strong and positive association with bone mineral density.