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Sesamin, a lignan from sesame oil, has been shown to have antihypertensive and antioxidative properties. This study examined the effects of sesamin on oxidized low-density lipoprotein (oxLDL)-induced endothelial dysfunction. Oxidative stress was determined by measuring the generation of intracellular reactive oxygen species (ROS) and by measuring the expression levels of superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS). To assess the pro-inflammatory effects of oxLDL, ELISA was used to detect IL-8 expression, endothelin-1 (ET-1) secretion, and nuclear factor-kappaB (NF-kappaB) activation. The expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was examined by flow cytometry. In addition, several apoptotic signaling pathways were also investigated. The data showed that sesamin significantly ameliorated oxLDL-induced ROS generation and SOD-1 inactivation. Sesamin also attenuated the oxLDL-induced activation of NF-kappaB, suggesting that the inhibitory effects of sesamin on IL-8 and ET-1 release, adhesion molecule expression, and the adherence of THP-1 cells were at least partially through the blockade of NF-kappaB activation. Furthermore, sesamin attenuated oxLDL-induced apoptotic features, such as intracellular calcium accumulation and the subsequent collapse of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3. Results from this study may provide insight into possible molecular mechanisms underlying sesamin's beneficial effects against oxLDL-mediated vascular endothelial dysfunction.

Atherosclerosis is a chronic inflammatory process with increased oxidative stress in vascular endothelium. Ginkgo biloba extract (GbE), extracted from Ginkgo biloba leaves, has commonly been used as a therapeutic agent for cardiovascular and neurological disorders. The aim of this study was to investigate how GbE protects vascular endothelial cells against the proatherosclerotic stressor oxidized low-density lipoprotein (oxLDL) in vitro. Human umbilical vein endothelial cells (HUVECs) were incubated with GbE (12.5–100 μg/ml) for 2 h and then incubated with oxLDL (150 μg/ml) for an additional 24 h. Subsequently, reactive oxygen species (ROS) generation, antioxidant enzyme activities, adhesion to monocytes, cell morphology, viability, and several apoptotic indexes were assessed. Our data show that ROS generation is an upstream signal in oxLDL-treated HUVECs. Cu,Zn-SOD, but not Mn-SOD, was inactivated by oxLDL. In addition, oxLDL diminished expression of endothelial NO synthase and enhanced expression of adhesion molecules (ICAM, VCAM, and E-selectin) and the adherence of monocytic THP-1 cells to HUVECs. Furthermore, oxLDL increased intracellular calcium, disturbed the balance of Bcl-2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by GbE ( P < 0.05). Results from this study may provide insight into a possible molecular mechanism underlying GbE suppression of the oxLDL-mediated vascular endothelial dysfunction.

Backgrounds Adiponectin is thought to protect against atherosclerosis and its expression is decreased in metabolic syndrome and diabetes mellitus. Adiponectin has a high-molecular-weight (HMW) multimer structure in the blood. We determined whether circulating HMW adiponectin, total adiponectin, or their ratio predicts baseline angiographic coronary artery disease (CAD) severity and restenosis after percutaneous coronary intervention (PCI). Methods Patients with stable angina pectoris who underwent PCI for a de novo lesion and had angiographic follow-up at our hospital were retrospectively enrolled. The study patients were grouped as moderate (N = 68) or severe (N = 63) coronary atherosclerosis by the baseline median Gensini severity score (moderate Results Univariate analysis showed that subjects in the severe CAD group had a lower HMW/total adiponectin ratio (0.32 ± 0.19 vs. 0.37 ± 0.16, p = 0.024) while the absolute value of HMW adiponectin (2.17 ± 2.05 vs. 2.27 ± 2.07 µg/ml, p = 0.389) and total adiponectin (5.97 ± 3.12 vs. 5.76 ± 2.91 µg/ml, p = 0.807) were similar between the severe and moderate CAD groups. In a multivariate binary logistic regression model, a higher serum HMW/total adiponectin ratio (odds ratio 0.058, p = 0.018) was negatively, while hypercholesterolemia (OR 2.475, p = 0.029) was positively associated with coronary atherosclerosis disease severity. In terms of restenosis after PCI (mean follow-up at 12 ± 13 months), HMW adiponectin, total adiponectin and their ratio were similar between restenotic (N = 91) and non-restenotic groups (N = 40). Conclusions A decreased ratio of circulating HMW adiponectin to total adiponectin is associated with angiographic disease severity but not restenosis in CAD patients undergoing PCI.

Statin, a potent lipid-lowering agent, ameliorates the interaction of monocytes and endothelium, a critical step in the atherosclerotic process. However, it remains unclear whether this effect of statin depends on different doses or the presence of metabolic syndrome. In this prospectively double-blind study, 21 hypercholesterolemia subjects, with low-density lipoprotein cholesterol between 130 and 170 mg/dL, received low-dose (10 mg/d) or high-dose (40 mg/d) pravastatin treatment for 8 weeks. We assessed the reduction of monocyte adhesion to cultured endothelium between different-dose groups and the relationship to metabolic syndrome. Total cholesterol and low-density lipoprotein cholesterol were significantly decreased after 40-mg pravastatin treatment (−23.3% ± 3.7%, P < .001 and −28.8% ± 3.0%, P < .001), and the reductions were greater than those in the 10-mg group (P = .041 and P = .045, respectively). There was no significant difference in monocyte adhesion between high-dose and low-dose pravastatin treatment. When all subjects were divided into an improvement group and a no improvement group, according to the median of change percentage of monocyte adhesion after pravastatin treatment, there were significantly more subjects with metabolic syndrome in the no improvement than the improvement group (6 vs 1 person, P =.024). Using logistic regression analysis, metabolic syndrome, rather than dose effect of pravastatin, was an independent predictor of interaction between monocytes and endothelium (95% confidence interval = 0.001-0.865, P = .041). Attenuating adhesion between monocytes and endothelium is altered by the presence of metabolic syndrome when hypercholesterolemia subjects receive pravastatin treatment.

The role of adiponectin, a marker of the metabolic syndrome, on the pathogenesis of hypertension in comparison with markers of adipose tissue mass (leptin) and inflammation (high-sensitivity C-reactive protein [hs-CRP]) remains to be clarified. The eligible study population consisted of 2,045 residents agedor =40 years who had participated in a community-based survey and had complete data for serum adiponectin, leptin, and hs-CRP, and for whom homeostasis model assessment of insulin resistance (HOMA-IR) had been calculated from insulin and plasma glucose. Among all eligible participants, as well as in the subgroup of nondiabetic normotensives (blood pressure140/90 mmHg and without antihypertensive medication), all three markers were significantly correlated with systolic blood pressure (negative correlation for adiponectin and positive correlations for leptin and hs-CRP). Among all participants, systolic blood pressure and the presence of hypertension were determined mainly by age, sex, body mass index, and waist circumference. None of the markers further contributed to the multivariate linear regression or logistic regression models. In contrast, adiponectin, but not leptin, hs-CRP, or HOMA-IR, was significantly associated with systolic blood pressure and the presence of pre-hypertension (blood pressure within 120-139/80-89 mmHg) after adjustment for age, sex, body mass index, and waist circumference in the nondiabetic normotensive subgroup. Similarly, adiponectin was independently associated with diastolic blood pressure in the nondiabetic normotensive subgroup but not in the whole population. In conclusion, adiponectin, but not leptin or hs-CRP, was independently associated with blood pressure in a nondiabetic normotensive subgroup.

Aims We conducted a prospective study to determine the risk factors for decrease in ABI in Chinese subjects with type 2 diabetes during a 3-year period. Methods Type 2 diabetic subjects with normal ABI were enrolled in this study. The risk factors for PVD and ABI were examined before and after the follow-up period. Results A total of 107 type 2 diabetic subjects completed the assessment. Based on the change of ABI, the study subjects were divided into two groups. Forty subjects, in Group 1, had a decrease in ABI; 67 subjects, in Group 2, had no decrease in ABI after the 3-year follow-up. The baseline total-to-HDL cholesterol ratio (4.5±1.2 vs. 3.9±1.0, P =0.018) and serum creatinine (99.0±18.0μmol/L vs. 88.8±15.7μmol/L, P =0.004) were significantly higher, and the HDL cholesterol concentration was significantly lower (1.11±0.26mmol/L vs. 1.27±0.39mmol/L, P =0.011) in Group 1 than in Group 2. Furthermore, total-to-HDL cholesterol ratio was the variable showed an inverse correlation and independent predictor for the change in ABI after the 3-year follow-up. Conclusions Total-to-HDL cholesterol ratio is a major risk factor for PVD and showed an inverse trend to change in ABI in Asian type 2 diabetic subjects.

Background Metabolic syndrome is gaining more attention as a special cluster of cardiovascular risks. However, its role, with or without diabetes, in predicting atherosclerosis progression, remains largely undetermined. We investigated the predictors for angiographic coronary atherosclerosis progression in patients with metabolic syndrome and angina pectoris. Methods Patients with metabolic syndrome and angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of first catheterization were enrolled for analysis ( N = 113). A modified Gensini scoring system was used to define CAD progression between the index and follow-up angiograms. Those who had significant angiographic progression of coronary disease were classified as the progression group ( N = 42) and those who did not as the non-progression group ( N = 71). Results There were more cases of diabetes mellitus (52% vs. 31%, p = 0.040) in the CAD progression group. The progression group also had higher baseline fasting blood glucose (150 ± 73 vs. 117 ± 46 mg/dl, p = 0.010) but similar LDL cholesterol (114 ± 38 vs. 109 ± 33 mg/dl, p = 0.421) than the non-progression group. In terms of inflammatory markers, there was no difference in hs-CRP ( p = 0.208), MCP-1 ( p = 0.514), or sCD40L ( p = 0.549) between the groups. In binary logistic regression, diabetes mellitus remained a significant predictor of CAD progression (OR 2.43, p = 0.030) for patients with metabolic syndrome and angina pectoris, but hs-CRP and LDL-C were not. Conclusion Diabetes mellitus, but not inflammatory marker hs-CRP or LDL-C, is a significant predictor of angiographic CAD progression in patients with metabolic syndrome and angina pectoris.

Metabolic syndrome, which involves different pathological mechanisms in associated disorders including inflammation, endothelial dysfunction, and insulin resistance, results in the development of cardiovascular diseases. The effect of the accumulative abnormalities of metabolic components and the relationship of each component to these associated disorders have not been clearly delineated. We therefore conducted a cross-sectional study to investigate the accumulative effect and the correlation of components of the metabolic syndrome to C-reactive protein (CRP), urinary albumin excretion (UAE), and the homeostasis model assessment for insulin resistance index (HOMA-IR). A total of 200 nondiabetic subjects received assessment of metabolic syndrome and measurements of serum CRP, UAE, and HOMA-IR. As the number of abnormalities of metabolic syndrome increased in subjects, the CRP, UAE, and HOMA-IR were significantly elevated (P value for trend less than .001, all). Waist circumference was an independent risk factor for CRP (P = .012); waist circumference and systolic blood pressure were independent risk factors for UAE (P = .010 and P < .001, respectively); and waist circumference, triglyceride, and glucose were independent risk factors for HOMA-IR (P < .001, all). More metabolic abnormalities were associated with higher risk of inflammation, urinary albumin, and insulin resistance. Waist circumference was the only independent risk factor for all 3 associated diseases in metabolic syndrome.

Adipocyte cytokines regulate glucose metabolism and insulin resistance and adiponectin is thought to have a protective effect against atherosclerosis. Studies have shown that adiponectin expression is decreased in obese subjects and those with metabolic syndrome or diabetes mellitus. The purpose of this study was to investigate the relationship between circulating adipocyte cytokine concentrations and angiographic coronary artery disease (CAD) progression in patients with chest pain. Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of first catheterization between March 1999 and January 2004 were enrolled. A modified Gensini scoring system was used to define angiographic coronary artery progression between the index and follow-up angiograms. Those who had significant angiographic progression of coronary lesions were classified into the progression group (N=55). Those who did not have CAD progression were classified into the non-progression group (N=102). Univariate analysis showed that CAD progression was associated with male gender (93% vs. 78%, p=0.038), higher baseline total cholesterol (187+/-43 vs. 173+/-39 mg/dl, p=0.037) and higher baseline fasting blood glucose (128+/-57 vs. 110+/-40 mg/dl, p=0.037). Patients in the progression group had a significantly lower serum adiponectin level (14.3+/-7.9 vs. 18.9+/-13.2 mug/ml, p=0.007) than, but resistin (28.9+/-13.4 vs. 34.4+/-26.0 ng/ml, p=0.142) and leptin (7.4+/-4.6 vs. 7.7+/-6.5 ng/ml, p=0.675) levels similar to, those in the non-progression group. In a multivariate binary logistic regression model, male gender (odds ratio 4.283, p=0.015), higher serum cholesterol (odds ratio 1.010, p=0.032) and lower serum adiponectin (odds ratio 0.959, p=0.030) were all significant independent predictors of CAD progression. In conclusion, we found that a decreased circulating level of adiponectin is associated with angiographic CAD progression in patients with angina pectoris.

Variants at chromosome 9p21 are associated with coronary artery disease (CAD). However, the longitudinal effects of 9p21 variants on cardiovascular mortality remain controversial and may depend on whether the patient has CAD. We tested the hypothesis that the single-nucleotide polymorphism (SNP) rs4977574 is associated longitudinally with cardiovascular death in patients without detectable coronary lesions. We enrolled patients who underwent coronary angiography for angina pectoris but had normal angiographic findings. Laboratory analyses and rs4977574 TaqMan genotyping were performed using fasting blood samples collected during hospitalization. Cardiovascular and all-cause mortality rates were acquired from a national database. Among the 679 enrolled subjects with neither myocardial infarction nor an angiographic coronary lesion, 28 (19.0%) of the 147 homozygous GG carriers suffered a cardiovascular death, compared with 63 (11.8%) of the 532 subjects with the AG or AA genotype during the median 12.3 years (interquartile range 8.6-12.7 years) of follow-up. In a recessive model, cardiovascular mortality was significantly higher in subjects with the GG genotype than in those with the other genotypes (hazard ratio, 1.69, 95% confidence interval 1.08 to 2.64; P = 0.021). In this follow-up study, rs4977574, a tag SNP at chromosome 9p21, was shown to be associated with cardiovascular mortality in Taiwanese patients with angina pectoris but no coronary lesions.

Although serum leptin concentrations are reported by several studies to increase in patients with liver cirrhosis, the mechanisms underpinning this increase remain unclear. Circulating tumor necrosis factor alpha (TNF-alpha) concentrations are also recognized to increase in liver cirrhosis. Furthermore, TNF-alpha administration to rodents results in increased expression and secretion of leptin from adipose tissue in a manner dependent on type 1 TNF-alpha receptor (TNF-RI). The present study was undertaken to examine adipose leptin expression and to explore potential relationships between leptin expression and TNF-alpha in subjects with liver cirrhosis. Liver cirrhosis was induced in male Sprague-Dawley rats by dimethylnitrosamine (DMN) administration or by common bile duct ligation (BDL). Ad libitum and pair-fed animals constituted controls. Serum leptin and TNF-alpha concentrations were determined by immunoassay. Gene expression was determined by the reverse transcription-polymerase chain reaction, and protein levels were measured by Western blotting. Serum leptin values after adjustment of body fat mass in DMN-treated rats were significantly higher than in pair-fed or ad libitum groups. Leptin mRNA and protein levels in epididymal fat in DMN rats increased by 1.8-fold and 2.3-fold, respectively, as compared with ad libitum controls, and by 4-fold and 6-fold, respectively, as compared with the pair-fed group. Epididymal TNF-alpha and membranous TNF-RI (mTNF-RI) concentrations were both 2.3 times higher in DMN rats than in ad libitum controls but did not differ between ad libitum and pair-fed groups. Adipose leptin protein levels correlated directly with TNF-alpha and mTNF-RI concentrations in combined DMN, ad libitum, and pair-fed rats (r=0.64 and r=0.49, respectively; P

Insulin resistance plays an important role in the pathogenesis of coronary artery disease (CAD). Thus, there is a need for accurate and accessible tools for measurement of insulin sensitivity in patients with this disease. This study explored the relationship between several surrogate estimates of insulin sensitivity in non-diabetic patients with angiographic evidence of CAD.The study population consisted of 1363 non-diabetic subjects with angiography results which revealed evidence of CAD in 660 and no evidence of CAD in 703 subjects. After overnight fasting, blood samples were drawn for determination of glucose and insulin concentrations in order to determine the homeostasis model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). In addition, steady-state plasma glucose (SSPG) concentrations obtained from insulin suppression tests were carried out in 54 subjects with and 194 subjects without CAD. The correlation of QUICKI with other surrogate estimates of insulin sensitivity in obese and non-obese subjects was also evaluated.The QUICKI correlated significantly with other methods for estimating insulin sensitivity in the CAD and non-CAD groups. The QUICKI also had a closer correlation with SSPG and log fasting plasma insulin (log FPI) in subjects with CAD (r = -0.573 and -0.869, respectively) than HOMA-IR (r = 0.508 and 0.777, respectively). QUICKI had a closer correlation with SSPG in the obese subjects than in the non-obese subjects, irrespective of the presence of CAD.The QUICKI was more closely related with SSPG, insulin area, and log FPI than other measurements of insulin sensitivity. These findings suggest that the QUICKI may provide a convenient, efficient method to measure insulin sensitivity in non-diabetic patients with CAD.

The interaction of leukocytes and endothelium plays an important role in the development of atherosclerosis. Previous studies found that adhesion of leukocytes to endothelium is greater in subjects with hypercholesterolemia. It is not clear if metabolic syndrome, a contributing risk factor of cardiovascular disease, is related to this adhesion. Therefore, we conducted a study, in which 48 nondiabetic subjects were enrolled, to determine the relationship between leukocyte adhesion and the components of metabolic syndrome. After a 12-hour overnight fast, subjects' fasting blood was obtained for measurement of lipoprotein concentrations and glucose and insulin levels. Results of the number of monocyte adhesion to human umbilical vein endothelial cells were divided into high monocyte adhesion group and low monocyte adhesion group (n = 24 in each group). Plasma concentrations of total cholesterol (245 ± 5 vs 229 ± 4 mg/dL, P = .021) and low-density lipoprotein cholesterol (LDL-C) (162 ± 4 vs 146 ± 3 mg/dL, P = .003) were both higher in the high monocyte adhesion group than in the low monocyte adhesion group. Monocyte adhesion was significantly correlated to plasma concentrations of LDL-C ( r = 0.407, P = .002) but not to the total cholesterol ( r = 0.202, P = .085). However, there was no difference in monocyte adhesion to endothelium between subjects with or without metabolic syndrome, based on the modified criteria from the Adult Treatment Panel III of the National Cholesterol Education Program. Insulin resistance index, presented as homeostasis model assessment insulin resistance, and glucose or insulin responses to oral glucose tolerance test were similar between groups. Our study demonstrated that monocyte adhesion to endothelium has a stronger relationship with the plasma concentration LDL-C than with characteristics of metabolic syndrome.

People with the metabolic syndrome are at increased risk for developing diabetes mellitus and coronary artery disease (CAD). This study assessed the 5 risk factors of metabolic syndrome in non-diabetic individuals with angiographically-documented CAD.To estimate the CAD risk associated with metabolic syndrome, we examined the 5 components of metabolic syndrome, defined by the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP) III, including blood pressure (or = 130/85 mm Hg), fasting glucose (or = 110 mg/dL), fasting triglycerides (or = 150 mg/dL), high-density lipoprotein (HDL) cholesterol level (men40 mg/dL; women50 mg/dL), and abdominal obesity (waist circumference defined by the Department of Health, Taiwan: men90 cm; women80 cm) among 139 non-diabetic patients with angiographically-documented CAD and 139 age- and gender-matched non-diabetic control subjects.Metabolic syndrome was found to be more prevalent in subjects with CAD than subjects without CAD (51.8% vs 18.7%; p0.001). Multiple logistic regression analysis showed that hypertension was the strongest predictor of CAD, followed by higher fasting glucose and lowered HDL cholesterol. These 5 factors accounted for 41.3% of total risk for CAD without diabetes.Our data revealed that the prevalence of metabolic syndrome was higher in this group of patients with angiographically-diagnosed CAD without diabetes than in controls.

Background: Psychological disturbances are well-known disorders in patients with hyperthyroidism, with anxiety and depression being the most commonly described. Stressful life events may play an important role in the relationship of anxiety, depression and hyperthyroidism. We assessed the associations of these disorders by three-part rating scales, including the Hamilton Rating Scale for Anxiety (HAM-A) indicating anxiety, the Zung Self-Rating Depression Scale (Zung Scale) indicating depression and the Social Readjustment Rating Scale (SRRS) indicating external stress from life events in this study. Methods: Eighty-six outpatients who visited an endocrine clinic with suspicion of thyroid disease and 18 healthy volunteers were enrolled in the study. In all of these individuals, thyroid functions were assessed and questionnaires were completed during an interview. Results: The outpatients with hyperthyroidism (n = 39) had higher scores of HAM-A (15.7 ± 1.1 vs. 8.0 ± 0.8, p < 0.001), Zung scale (46.2 ± 1.5 vs. 37.5 ± 1.4, p < 0.001) and SRRS (92.9 ± 13.5 vs. 56.9 ± 8.4, p = 0.015) than those with euthyroidism (n = 47). The scores of the three-part rating scales were also higher in the outpatients with hyperthyroidism than in healthy volunteers (n = 18), with no significant differences between the outpatients with euthyroidism and healthy volunteers. Conclusion: In patients with hyperthyroidism, anxiety, depression and stressful life events were more severe than in those with normal thyroid function. There were no correlations between these psychological disorders and thyroid function tests of the subjects with hyperthyroidism. The role of psychotherapy in the development of hyperthyroidism deserves further investigations.

High-sensitivity C-reactive protein (hs-CRP) is positively associated with the prevalence of coronary artery disease by epidemiologic data. Prospective studies indicate that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduced the plasma hs-CRP concentration and the risk of recurrent coronary events after myocardial infarction. Type 2 diabetes is associated with high mortality risk of coronary heart disease and this high risk may be involved in the inflammatory factors. We have therefore conducted a prospective study to assess whether simvastatin can rapidly reduce the plasma hs-CRP concentration in type 2 diabetic patients with hyperlipidemia. Seventeen type 2 diabetic patients with hyperlipidemia were enrolled in the study after 6 weeks on a lipid-lowering diet. Fourteen patients completed the study, taking simvastatin 20 mg daily for 8 weeks. Fasting blood samples were collected from each patient before and after 8-week administration of simvastatin. In response to 8-week administration of simvastatin, hs-CRP levels significantly decreased from 0.312+/-0.057 to 0.193+/-0.045 mg/dl (P.01). Plasma LDL cholesterol also decreased significantly from 130+/-9 to 74+/-3 mg/dl (P=.001). This study shows that plasma hs-CRP concentration can be reduced by 8-week administration of simvastatin in type 2 diabetic patients with hyperlipidemia.

It is well established that, as a group, patients with essential hypertension are characterized by insulin resistance. Previous studies have shown that a biallelic polymorphism in the tumor necrosis factor (TNF)[alpha ] promoter position [ndash ]308 and [ndash ]238 might be involved in the insulin resistance state in diabetic and/or nondiabetic subjects. We determined these polymorphisms in 235 nondiabetic hypertensive subjects and 246 unrelated normotensive controls. Fasting plasma glucose, insulin, lipoprotein, leptin, and TNF[alpha ] concentrations were measured, in addition to plasma glucose and insulin responses to a 75-g oral glucose tolerance test (OGTT). Insulin sensitivity was also determined by an insulin suppression test in 69 hypertensive and 76 normotensive individuals. The results showed no association of these genotypic distributions between hypertensive and normotensive individuals both at [ndash ]308 (GG, GA, and AA were 80.9%, 17.9%, and 1.3% in hypertensives, 84.2%, 15.4%, and 0.4% in normotensives, [Chi ] 2 = 1.68, P = .432) and at [ndash ]238 (GG, GA, and AA were 98.3%, 1.7%, and 0% in hypertensives, 96.7%, 3.3%, and 0% in normotensives, [Chi ] 2 = 1.19, P = .276) sites. These results did not change even after adjustment for values of age and body mass index (BMI). Anthropometric measurements, fasting plasma glucose, insulin, lipoprotein concentrations, glucose, and insulin responses to OGTT, TNF[alpha ], and leptin concentrations were similar between the genotype at the [ndash ]308 site both in hypertensive and normotensive groups. Insulin sensitivity, either measured by an insulin suppression test or homeostasis model assessment (HOMA) index, did not differ between the genotype at the [ndash ]308 site in subjects with hypertension or normotension. Fasting plasma TNF[alpha ] (10.2 [alpha ] 0.5 pg/mL v 10.1 [plusmn] 0.5 pg/mL, P = .928) concentrations did not differ between hypertensive and normotensive subjects even after adjustment for body fat and BMI values. We conclude that TNF[alpha ] promoter gene polymorphisms at position -238 and -308 do not play a major role in the pathogenesis of insulin resistance in Chinese subjects with or without hypertension.

Objective To investigate whether the increased homocysteine levels occur in the first 6 months postoperatively, when nutritional intake is the most inadequate and weight reduction is the most drastic. Patients and Methods Fasting glucose, insulin, lipoprotein, homocysteine, folic acid and vitamin B12 levels and oral glucose tolerance test (OGTT) were determined in 12 morbidly obese subjects (3 men and 9 women with a mean age of 31±3 years, mean±SEM) before, 6 and 12 months after banded gastroplasty. Results Gastroplasty resulted in significant weight loss, from 12±16 to 92±6 and 88±7 kgs, 6 and 12 months postoperatively (all p

Recent studies have shown that statins are effective in reducing fasting low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels. However, it remains unknown if treatment with statins also lowers daily postprandial triglyceride concentrations, which may promote atherogenesis in type 2 diabetes subjects. Forty-one subjects with type 2 diabetes and combined hyperlipidemia who had stable glycemic control were randomly assigned to take simvastatin 20 mg (n = 27) or a placebo (n = 14) once daily for 12 weeks. The medication dosage was doubled after 4 weeks if a subject's LDL-C was not less than 130 mg/dL. Among these participants, 24 subjects (15 on simvastatin and 9 on placebo) agreed to take a meal tolerance test with isocaloric mixed meals (carbohydrate, 52%; fat, 33%, and protein, 15% of the daily caloric intake) and daytime hourly blood sampling from 8 AM to 4 PM. Simvastatin treatment reduced the fasting total cholesterol level from 237 +/- 5 to 178 +/- 6 mg/dL (-25%), the LDL cholesterol level from 150 +/- 6 to 87 +/- 5 mg/dL (-40%), and raised high-density lipoprotein-cholesterol (HDL-C) level from 36 +/- 2 to 40 +/- 2 mg/dL (+11%) (all P

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean +/- SEM, 8.1 +/- 0.6 v 6.8 +/- 0.2 micromol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 +/- 0.5 v 7.2 +/- 0.5 v 8.4 +/- 0.6 micromol/L; P = .148) or normotensive subjects (6.3 +/- 0.4 v 8.0 +/- 0.8 v 7.0 +/- 0.8 micromol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.

It has been shown that insulin resistance syndrome, including glucose intolerance, dyslipidemia, and hypertension, is frequently associated with coronary artery disease (CAD). However, their relative contributions and predictive power in the development of CAD are still unclear, particularly in persons without diabetes.We examined these risk factors between 96 patients without diabetes but with angiographically documented CAD and 96 age-, sex-, and body mass index-matched healthy control subjects. Fasting plasma lipoprotein, glucose, and insulin concentrations in response to a 75-g oral glucose tolerance test were determined, and insulin sensitivity was measured by the insulin suppression test.Patients with CAD had significantly higher values of fasting glucose, glucose and insulin responses to oral glucose tolerance test, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride and decreased high-density lipoprotein (HDL) cholesterol concentrations compared with those of healthy people (P0.02-0.001). Although the steady-state plasma insulin values were similar in both groups, the steady-state plasma glucose (SSPG) concentrations were significantly higher in patients with CAD (12.2+/-0.4 versus 8.1+/-0.4 mmol/L, P0.001) compared with healthy subjects. When HDL0.9 mmol/L, LDL cholesterolor = 4.1 mmol/L, triglycerideor = 2.3 mmol/L, SSPGor = 10.5 mmol/L, and presence of hypertension were defined as separate risk factors for CAD, significantly higher odds-ratio values were observed in patients with CAD compared with healthy people. From logistic multiple regression analysis, SSPG was the strongest risk, followed by lowered HDL cholesterol, elevated triglyceride and LDL cholesterol, and hypertension, to predict CAD. These 5 factors accounted for 36% of total risk for development of CAD in persons without diabetes.Patients without diabetes with CAD have abnormal glucose metabolism, hyperinsulinemia, and insulin resistance. Degree of insulin resistance (SSPG values), plasma lipid values, and history of hypertension together accounted for one third of all risk for CAD, although degree of insulin resistance was the strongest risk factor.