Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study

Background and AimRecent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women.We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women.Methods and ResultsThe parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54 mg of genistein aglycone (n = 71) or placebo (n = 67), daily. Both arms received calcium and vitamin D₃ in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured.Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group.ConclusionsAfter 3-years of treatment, genistein aglycone plus calcium, vitamin D₃ and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.     

Effects of nasal continuous positive airway pressure on soluble cell adhesion molecules in patients with obstructive sleep apnea syndrome

PURPOSE: Obstructive sleep apnea syndrome is common in middle-aged men and may be associated with an increased risk of cardiovascular disease. We investigated the effect of nasal continuous positive airway pressure (CPAP) treatment on levels of soluble cell adhesion molecules-which have been shown to be associated with the development of atherosclerosis-in these patients. SUBJECTS AND METHODS: We studied 23 patients with obstructive sleep apnea syndrome diagnosed by polysomnography who were treated with nasal CPAP. Serum soluble intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 levels were measured before nasal CPAP was started, and after 3 or 4 days (n = 19), 1 month (n = 23), or 6 months (n = 11) of treatment. RESULTS: After 3 to 4 days of nasal CPAP therapy, the mean (+/- SD) soluble E-selectin level had decreased from 89 +/- 44 ng/mL to 69 +/- 28 ng/mL (P = 0.002). After 1 month, the soluble intercellular adhesion molecule-1 level had decreased from 311 +/- 116 ng/mL to 249 +/- 74 ng/mL (P = 0.02). After 6 months, soluble vascular cell adhesion molecule-1 levels had not changed significantly, while the mean soluble intercellular adhesion molecule-1 level (212 +/- 59 ng/mL) had decreased further (P = 0.02). Before treatment, soluble intercellular adhesion molecule-1 levels and the apnea and hypopnea index were correlated (r = 0.43, P = 0.04). CONCLUSIONS: Obstructive sleep apnea and hypopnea have a significant adverse effect on serum soluble cell adhesion molecule-1 levels that may be reduced by nasal CPAP treatment.     

Effects of antioxidant supplementation on insulin sensitivity, endothelial adhesion molecules, and oxidative stress in normal-weight and overweight young adults

The objective of the study was to determine whether short-term antioxidant (AOX) supplementation affects insulin sensitivity, endothelial adhesion molecule levels, and oxidative stress in overweight young adults. A randomized, double-blind, controlled study tested the effects of AOXs on measures of insulin sensitivity (homeostasis model assessment [HOMA]) and quantitative insulin sensitivity check index), endothelial adhesion molecules (soluble intercellular adhesion molecule-1, vascular adhesion molecule, and endothelial-leukocyte adhesion molecule-1), adiponectin, and oxidative stress (lipid hydroperoxides) in overweight and normal-weight individuals (N = 48, 18-30 years). Participants received either AOX (vitamin E, 800 IU; vitamin C, 500 mg; β-carotene, 10 mg) or placebo for 8 weeks. The HOMA values were initially higher in the overweight subjects and were lowered with AOX by week 8 (15% reduction, P = .02). Adiponectin increased in both AOX groups. Soluble intercellular adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1 decreased in overweight AOX-treated groups by 6% and 13%, respectively (P < .05). Plasma lipid hydroperoxides were reduced by 0.31 and 0.70 nmol/mL in the normal-weight and overweight AOX-treated groups, respectively, by week 8 (P < .05). Antioxidant supplementation moderately lowers HOMA and endothelial adhesion molecule levels in overweight young adults. A potential mechanism to explain this finding is the reduction in oxidative stress by AOX. Long-term studies are needed to determine whether AOXs are effective in suppressing diabetes or vascular activation over time.     

Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels

OBJECTIVE: Although androgen replacement has been shown to have beneficial effects in hypogonadal men, there is concern that androgens may deleteriously affect cardiovascular risk in elderly men. DESIGN: Anastrozole is an oral aromatase inhibitor that normalizes serum testosterone levels and decreases oestradiol levels modestly in elderly men with mild hypogonadism. Thirty-seven elderly hypogonadal men were randomized to receive either anastrozole 1 mg daily (n = 12), anastrozole 1 mg twice weekly (n = 11), or daily placebo (n = 14) for 12 weeks in a double-blind fashion. PATIENTS: Men aged 62-74 years with mild hypogonadism defined by testosterone levels less than 350 ng/dl. MEASUREMENTS: Serum levels of fasting lipids, C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and homeostatic model assessment (HOMA) scores were measured at 4-week intervals. RESULTS: Treatment with anastrozole did not significantly affect fasting lipids, inflammatory markers (IL-6, CRP), adhesion molecules (ICAM-1, VCAM-1) or insulin sensitivity (HOMA). There was, however, a positive correlation between changes in serum triglycerides and changes in serum oestradiol levels (P = 0.04). CONCLUSIONS: While short-term administration of anastrozole is an effective method of normalizing serum testosterone levels in elderly men with mild hypogonadism, it does not appear to adversely affect lipid profiles, inflammatory markers of cardiovascular risk or insulin resistance.     

Endothelial activation and inflammation in prepubertal obese Turkish children

To investigate the degree of endothelial activation and inflammation in prepubertal obese children and to determine the relationship between the markers of endothelial activation, inflammation, and cardiovascular risk factors. In 30 obese and 28 healthy prepubertal children, soluble intercellular adhesion molecule-1 and endothelial leukocyte adhesion molecule-1 (sE-selectin) as markers of endothelial activation and soluble vascular cell adhesion molecule-1 (sVCAM-1) and C-reactive protein (CRP) as markers of endothelial inflammation in addition to cardiovascular risk factors including blood lipids, glucose, insulin, hemoglobin A1c, and systolic and diastolic blood pressure were investigated and compared. The tests were repeated after an oral glucose tolerance test in the obese group. Fasting CRP levels were found to be significantly higher in obese children. Vascular cell adhesion molecule-1 levels were found to be significantly increased in obese children after oral glucose tolerance test. Fasting CRP was positively correlated with body mass index (BMI) and low-density lipoprotein, whereas sE-selectin was positively correlated with total cholesterol. In the obese group, postload levels of soluble sE-selectin was positively correlated with low-density lipoprotein; sVCAM-1 was positively correlated with insulin and homeostasis model assessment values. Postload soluble intercellular adhesion molecule-1, sVCAM-1, and soluble sE-selectin levels were also positively correlated with each other. In the fasting state, BMI was the significant independent risk factor for CRP, and total cholesterol was the significant risk factor for soluble sE-selectin. Insulin resistance was the significant independent risk factor for postload sVCAM-1, and postload low-density lipoprotein stood as the significant independent risk factor for postload soluble sE-selectin. Endothelial inflammation is present in obese prepubertal children and is mainly associated with insulin resistance and lipid levels as well as BMI.     

Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy

Subclinical hypothyroidism is associated with an increased risk of atherosclerosis. The aim of this study was to investigate the concentration of plasma soluble intercellular adhesion molecule-1 and adiponectin in relation to insulin sensitivity in patients with subclinical hypothyroidism and to estimate if L-thyroxine treatment had an influence on these parameters. 13 women with subclinical hypothyroidism and 14 euthyroid controls were included in the study. A physical examination was conducted, hyperinsulinemic euglycemic clamp and plasma soluble intercellular adhesion molecule-1, adiponectin and lipids profiles were measured at baseline in both groups and in the group with subclinical hypothyroidism the above procedures were performed after L-thyroxine therapy (mean time of treatment 5.0 months) in stable euthyroid state. Insulin sensitivity and adiponectin were not different at baseline in the two studied groups. Plasma soluble intercellular adhesion molecule-1 concentration was significantly higher in the patients with subclinical hypothyroidism (P = 0.011). The comparison of lipids profiles revealed that only LDL-cholesterol concentration was higher (P = 0.011) in the group with subclinical hypothyroidism. After therapy, we observed an improvement of insulin sensitivity (P = 0.012) and a decrease of plasma glucose (P = 0.019) and soluble intercellular adhesion molecule-1 (P = 0.01), whereas adiponectin concentration remained unchanged. We concluded that L-thyroxine treatment in patients with subclinical hypothyroidism might exert a beneficial effect by reducing cardiovascular risk factors.     

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.     

Effects of the phytoestrogen genistein on the circulating soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin system in early postmenopausal women

We investigated the serum levels of both receptor activator of nuclear factor kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) in postmenopausal healthy women after a 1-yr therapy with genistein, (n = 30; 54 mg/d), hormone replacement therapy (n = 30; 1 mg/d 17beta-estradiol combined with norethisterone acetate) and placebo (n = 30). By comparison with placebo, the soluble RANKL (sRANKL)/OPG ratio was lower in the genistein group (-69 +/- 7%; P < 0.01 vs. placebo 81 +/- 24%) and in hormone replacement therapy-treated women (-11 +/- 2%; P < 0.01 vs. placebo). A positive correlation (r = 0.63; P < 0.01) was found between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in urinary deoxypyridinoline, a bone resorption marker. A negative correlation was observed between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in femoral neck bone mineral density (r = -0.7; P < 0.01). Our findings suggest that the sRANKL-OPG system may mediate the beneficial effects of genistein on bone remodeling in postmenopausal women.     

Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women

OBJECTIVES: Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect. DESIGN: In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow-mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy. RESULTS: The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E-selectin and 13.9% for intercellular adhesion molecule-1 (ICAM-1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group. CONCLUSIONS: Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E-selectin and ICAM-1 in healthy postmenopausal women.     

Growth hormone reduces inflammation in postmenopausal women with abdominal obesity: a 12-month, randomized, placebo-controlled trial

CONTEXT: Abdominal obesity is associated with low GH secretion, elevated circulating markers of inflammation, and increased risk of cardiovascular disease. OBJECTIVE: The objective was to study the effect of GH treatment on inflammatory markers and vascular adhesion molecules in postmenopausal women with abdominal obesity. DESIGN: Forty women aged 51-63 yr received GH (0.67 mg/d) in a randomized, double-blind, placebo-controlled, 12-month trial. Measurements of inflammatory markers [highly sensitive C-reactive protein (CRP), IL-6, and amyloid polypeptideA] and markers of endothelial dysfunction (soluble E-selectin, vascular adhesion molecule-1, intercellular molecule-1, and matrix metalloproteinase-9) were performed at baseline and after 6 and 12 months of treatment. RESULTS: After 12 months, the mean IGF sd score was 0.9 +/- 1.5 and -0.8 +/- 0.6 in the GH and placebo groups, respectively. GH treatment reduced CRP and IL-6 levels compared with placebo (P = 0.03 and P = 0.05, respectively), whereas the markers of endothelial dysfunction were unaffected. Within the GH-treated group, a reduction was shown in CRP (4.3 +/- 4 to 3.0 +/- 3 mg/liter; P < 0.05) and in IL-6 (4.4 +/- 2 to 3.3 +/- 2 ng/liter; P < 0.01). In the GH-treated group, the decrease in CRP and IL-6 correlated with a reduction in visceral adipose tissue (r = 0.7, P < 0.001 and r = 0.5, P < 0.05, respectively). CONCLUSION: GH treatment in postmenopausal women with abdominal obesity reduced serum markers of systemic inflammation. Circulating markers of endothelial dysfunction were unaffected by treatment.     

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.     

Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial

OBJECTIVES: The UK Prospective Diabetes Study (UKPDS) showed that treatment with metformin decreases macrovascular morbidity and mortality independent of glycaemic control. We hypothesized that metformin may achieve this by improving endothelial function and chronic, low-grade inflammation. Data on this issue are scarce and we therefore tested, in the setting of a randomized, placebo-controlled trial, whether metformin can affect endothelial function and low-grade inflammation. DESIGN: The Hyperinsulinaemia the Outcome of its Metabolic Effects (HOME) trial is a double-blind trial, in which all patients were randomized to receive either metformin or placebo in addition to insulin therapy. At the beginning and the end of a 16-week treatment period fasting blood samples were drawn and a physical examination was carried out. SETTING: The trial was conducted in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden; the Netherlands). SUBJECTS: Patients were included if they were between 30 and 80 years of age; had received a diagnosis of diabetes after the age of 25; had never had an episode of ketoacidosis; and their blood glucose-lowering treatment previously consisted of oral agents but now only consisted of either insulin (n = 345) or insulin and metformin (n = 45). We excluded pregnant women and women trying to become pregnant, patients with a Cockroft-Gault-estimated creatinine clearance <50 mL min(-1), or low plasma cholinesterase (reference value <3.5 units L(-1)), patients with congestive heart failure (New York Heart Association class III/IV), or patients with other serious medical or psychiatric disease. A total of 745 eligible patients were approached; 390 gave informed consent and were randomized (196 metformin, 194 placebo). About 353 patients completed 16 weeks of treatment (171 metformin, 182 placebo). MAIN OUTCOME MEASURES: The HOME trial was designed to study the metabolic and cardiovascular effects of metformin during a follow-up of 4 years. Presented here are the results of an interim analysis after 16 weeks of treatment. RESULTS: When compared with placebo, metformin treatment was associated with an increase in urinary albumin excretion of 21% (-1 to +48; P = 0.06); a decrease in plasma von Willebrand factor of 6% (-10 to -2; P = 0.0007); a decrease in soluble vascular cell adhesion molecule-1 of 4% (-7 to -2; P = 0.0002); a decrease in soluble E-selectin of 6% (-10 to -2; P = 0.008); a decrease in tissue-type plasminogen activator of 16% (-20 to -12; P < 0.0001); and a decrease in plasminogen activator inhibitor-1 of 20% (-27 to -10; P = 0.0001). These changes could not be explained by metformin-associated changes in glycaemic control, body weight or insulin dose. Markers of inflammation, i.e. C-reactive protein and soluble intercellular adhesion molecule-1, did not change with metformin treatment. CONCLUSIONS: In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation.     

Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity

CONTEXT: It has been suggested that oxidative stress and endothelial dysfunction could play a role in the higher cardiovascular disease risk noted in the abdominally obese population. OBJECTIVE: The objective of this study was to describe the associations between abdominal fat accumulation, oxidative stress, and endothelial dysfunction in men. DESIGN: A complete physical and metabolic profile was assessed in a group of 56 men covering a wide range of adiposity and plasma oxidized low-density lipoprotein (OxLDL), and soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and C-reactive protein concentrations were determined. RESULTS: We found that abdominal visceral adipose tissue was positively associated with plasma OxLDL (r = 0.52; P < 0.0001) and C-reactive protein (r = 0.60; P < 0.0001) concentrations. We also found significant associations between plasma E-selectin levels and hyperinsulinemia (r = 0.39; P < 0.005) as well as with the homeostasis model assessment index of insulin resistance (r = 0.42; P < 0.005). CONCLUSIONS: Our study showed that plasma OxLDL levels and low-grade systemic inflammation are increased in men with a high visceral adipose tissue accumulation. Furthermore, our results support the notion that insulin resistance is associated with endothelial activation. Overall, our observations give us further insights on the increased cardiovascular disease risk frequently noted among viscerally obese, insulin-resistant individuals.     

Usefulness of preoperative C-reactive protein and soluble intercellular adhesion molecule-1 level for predicting future cardiovascular events after coronary artery bypass grafting

High levels of C-reactive protein and soluble intercellular adhesion molecule-1 are associated with increased risk for cardiovascular events. No long-term data are available on predictive value of preoperative levels of C-reactive protein and soluble intercellular adhesion molecule-1 on outcome after coronary artery bypass grafting. We measured baseline levels of C-reactive protein and soluble intercellular adhesion molecule-1 in preoperative serum stored at -80 degrees C in 87 patients with coronary artery disease before undergoing isolated coronary artery bypass grafting. Follow-up was performed after a mean duration of 7.6+/-0.1 years, and all cardiovascular events were recorded. Data were analyzed by categorizing patients into 2 groups according to median value of C-reactive protein and soluble intercellular adhesion molecule-1. During follow-up, 16 patients developed a cardiovascular event. In patients with C-reactive protein above the median (1.9 mg/L), the cumulative cardiovascular event incidence was 29% compared with 9% in patients with levels below the median (p=0.048). In Cox regression analysis that was corrected for age, gender, and conventional risk factors, the adjusted relative risk of cardiovascular events of C-reactive protein above the median was 3.9 (95% confidence interval 1.1 to 13.9, p <0.05). Soluble intercellular adhesion molecule-1 level above the median (136 microg/L) was associated with a cumulative cardiovascular event incidence of 21% versus 16% below the median (p=0.48). In conclusion, in patients who undergo coronary artery bypass grafting, high preoperative levels of C-reactive protein levels, but not of soluble intercellular adhesion molecule-1, were associated with long-term risk of cardiovascular events, independent of other cardiac risk factors.     

Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes

To investigate the relationships between serum concentrations of soluble adhesion molecules and hyperglycemia, insulin resistance, or other conventional risk factors in type 2 diabetes, we measured soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), insulin sensitivity, and conventional risk factors in 150 Japanese type 2 diabetic patients without apparent diabetic macroangiopathy. High serum concentrations of sVCAM-1 and sE-selectin were observed in patients with type 2 diabetes. Serum concentrations of soluble adhesion molecules were not significantly influenced by sex, hypertension, dyslipidemia, or microangiopathy. Spearman correlation showed that sVCAM-1 concentrations correlated significantly with fasting plasma glucose (FPG), fasting C-peptide, and insulin sensitivity [K index of the insulin tolerance test (K(ITT))] (rho=0.19,0.23, and -0.23, respectively). Soluble E-selectin concentrations correlated significantly with body mass index (BMI), FPG, fasting C-peptide, insulin sensitivity, and triglyceride (rho=0.33,0.42,0.26,-0.48, and 0.29, respectively). Multiple regression analysis showed that FPG, fasting C-peptide, and total cholesterol were independent factors that correlated with sVCAM-1 levels. BMI, FPG, and insulin sensitivity were independent factors that correlated with sE-selectin levels. Serum concentrations of sE-selectin significantly increased associated with clustering of conventional risk factors those obesity, hypertension, dyslipidemia, and current smoking (P<0.01). Thus, sVCAM-1 and sE-selectin levels are related to both hyperglycemia and insulin resistance. Soluble E-selectin levels may be related to obesity, hyperglycemia, and insulin resistance and may reflect the presence of a multiple risk factor clustering syndrome.     

不同糖耐量状态者血清SICAM-1和SVCAM-1水平与炎症相关性研究

按口服葡萄糖耐量试验结果,将研究对象分为正常糖耐量(NGT)组、单纯空腹血糖受损(IFG)组、单纯糖耐量受损(IGT)组、IFG与IGT并存(IFG/ICT)组及2型糖尿病(DM)组。采用酶联免疫吸附法(ELISA)分别检测上述人群的血清可溶性细胞间黏附分子1(SICAM-1)、可溶性血管细胞黏附分子1(SVCAM-1)和超敏C反应蛋白水平(hr-CRP),并与糖脂代谢指标和稳态模型胰岛素抵抗指数(HOMA- IR)作相关性分析。结果显示,血清SICAM-1、SVCAM-1和hs-CRP水平按分组顺序逐组升高,提示2型DM的发病过程与内皮细胞损伤和炎症状态有关。     

Effects of rosiglitazone on endothelial function in men with coronary artery disease without diabetes mellitus

Recent data have shown that peroxisome proliferator-activated receptor-gamma agonists may exert protective effects on the vascular endothelium by amelioration of insulin resistance and through direct anti-inflammatory effects. In this study we assessed the effect of rosiglitazone on biochemical and biophysical indexes of endothelial function in male, nondiabetic patients with coronary artery disease. Consecutive male subjects (n = 71) with clinically stable, angiographically documented coronary artery disease and without diabetes mellitus were investigated. Patients were randomized in a double-blind manner to placebo or rosiglitazone for a total of 24 weeks. Flow-mediated dilation (FMD) of the brachial artery, C-reactive protein, von Willebrand factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels, and parameters of glucose and lipid metabolism were measured at baseline and after 12 and 24 weeks of treatment. Rosiglitazone treatment significantly reduced C-reactive protein (median 0.56 mg/L [interquartile range 0.33 to 1.02] to 0.33 mg/L [interquartile range 0.26 to 0.40], p <0.01), von Willebrand factor (139 +/- 47 to 132 +/- 44 IU/dl, p = 0.02), insulin resistance index (p = 0.05), and mean low-density lipoprotein (LDL) density (p <0.001) compared with placebo. However, no significant differences were seen between the rosiglitazone and placebo groups with regard to brachial artery FMD, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1 levels. Rosiglitazone treatment significantly increased LDL (2.62 +/- 0.72 to 2.95 +/- 0.84 mmol/L, p = 0.03) and triglyceride (1.23 +/- 0.63 to 1.56 +/- 0.98 mmol/L, p = 0.04) levels. Thus, rosiglitazone reduced markers of inflammation and endothelial activation, but this did not translate into an improvement in FMD. Increased LDL and triglyceride levels may have played a role.     

Effects of oral soy protein on markers of inflammation in postmenopausal women with mild hypercholesterolemia

Background Nitric oxide (NO) may protect arteries against atherosclerosis, as suggested by experimental studies. Estrogen therapy enhances the bioactivity of NO in the vasculature of healthy postmenopausal women, but is not acceptable for long-term use by many women. Observational studies have demonstrated beneficial cardiovascular effects of soy protein in premenopausal and postmenopausal women. We examined whether the consumption of isolated soy protein may improve markers of vascular inflammation in postmenopausal women with hypercholesterolemia. Methods and Results In a randomized, double-blind, placebo-controlled, crossover study, 24 postmenopausal women with hypercholesterolemia received 25 g of soy protein or a placebo daily for 6 weeks, with treatment periods separated by 1 month. Markers of vascular inflammation were measured by enzyme-linked immunosorbent assay methods, including: soluble interleukin-2 receptor (sIL-2r), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). There was no effect of soy protein in comparison with placebo on the inflammatory markers: the sIL-2r level was 942.2 ± 335.3 pg/mL with soy protein and 868.5 ± 226.9 pg/mL with placebo (P = .311); E-selectin was 39.6 ± 16.5 ng/mL with soy protein and 42.1 ± 17.6 ng/mL with placebo (P = .323); P-selectin was 157.9 ± 67.9 ng/mL with soy protein and 157.5 ± 47.6 ng/mL with placebo, (P = .977); ICAM-1 was 266.0 ± 81.3 ng/mL with soy protein and 252.5 ± 82.7 ng/mL with placebo (P = .435); VCAM-1 was 402.7 ± 102.1 ng/mL with soy protein and 416.4 ± 114.8 ng/mL with placebo (P = .53). Conclusions Consumption of 25 g of isolated soy protein daily for 6 weeks does not substantially affect markers of vascular inflammation in postmenopausal women with hypercholesterolemia. (Am Heart J 2003;145:e7.)     

Obesity,and not insulin resistance,is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women

AIMS/HYPOTHESIS: Increased serum inflammatory markers have been found in obesity and insulin-resistant states, and could play a causative role in insulin resistance, atherosclerosis and cardiovascular disease. The polycystic ovary syndrome represents a human model of insulin resistance because both lean and obese polycystic ovary syndrome patients are insulin-resistant compared with non-hyperandrogenic women. We evaluated whether obesity, insulin resistance, or both, are related to the increased concentrations of inflammatory markers in pre-menopausal women. METHODS: We compared 35 patients with polycystic ovary syndrome and 28 healthy women, paired for BMI, prevalence of obesity and smoking. Measurements included serum inflammatory markers, BMI, waist-to-hip ratio, blood pressure, serum glucose, insulin, lipid and hormone concentrations, and insulin sensitivity index. RESULTS: The insulin sensitivity index was reduced in polycystic ovary syndrome patients compared with controls. However, no differences were observed between both groups in C-reactive protein, interleukin 6, tumour necrosis factor-alpha, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. When considering patients and controls as a whole, C-reactive protein and interleukin 6, were increased in obese subjects compared with lean women. Inverse correlations existed between insulin sensitivity index and C-reactive protein, interleukin 6, tumour necrosis factor-alpha, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. Only the weak correlation with C-reactive protein persisted after controlling for BMI. CONCLUSION/INTERPRETATION: Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women.