dimethylarginine and Metabolic-Syndrome

Postmenopausal women are at an increased risk of cardiovascular disease and metabolic syndrome as many risk factors are aggravated by menopause. Elevated levels of homocysteine, triglyceride and asymmetric dimethylarginine (ADMA) have been recognized as risk factors for metabolic syndrome. The present study aimed to investigate the effect of transdermal estrogen treatment on serum levels of atherogenic amino acids, homocysteine, triglyceride, high density lipoprotein (HDL) cholesterol and ADMA in women with surgical menopause.. A prospective study was conducted in 85 surgically menopausal Turkish women at the Department of Menopause of Dr Zekai Tahir Burak Women's Health Research and Education Hospital between March 2007 and March 2008. Subjects were divided into two groups: a treatment group (Group 1) and control (Group 2). Group 1 (n = 46) received transdermal estrogen while Group 2 (n = 39) received no treatment. Body mass index (BMI) and levels of serum homocysteine, ADMA, triglyceride and HDL cholesterol were analyzed postoperatively at the first visit (baseline) and 6th months.. The two groups did not differ in age, baseline BMI and levels of ADMA, homocysteine and triglyceride. In Group 1, values of serum ADMA, homocysteine, triglyceride and HDL cholesterol levels were not different at baseline and at the 6-month visit (p = 0.996, p = 0.564, p = 0.113 and p = 0.173, respectively). On the other hand, the baseline and the 6th month measurements of serum ADMA, homocysteine and HDL cholesterol levels were significantly different in Group 2 (p = 0.001, p = 0.001, and p = 0.023, respectively).. Transdermal estrogen treatment has a protective effect against the risk factors of metabolic syndrome (homocysteine, ADMA, HDL cholesterol) in surgically menopausal patients who have undergone surgery in the early premenopausal period.

Topics: Administration, Cutaneous; Adult; Arginine; Biomarkers; Body Mass Index; Cholesterol, HDL; Double-Blind Method; Estradiol; Fallopian Tubes; Female; Homocysteine; Humans; Hysterectomy; Menopause, Premature; Metabolic Syndrome; Middle Aged; Ovariectomy; Prospective Studies; Time Factors; Triglycerides

Metabolic syndrome (MetS) denotes a clustering of risk factors that may affect nitric oxide (NO) bioavailability and predispose to cardiovascular diseases, which are delayed by exercise training. However, no previous study has examined how MetS affects markers of NO formation, and whether exercise training increases NO formation in MetS patients. Here, we tested these two hypotheses. We studied 48 sedentary individuals: 20 healthy controls and 28 MetS patients. Eighteen MetS patients were subjected to a 3-month exercise training (E+group), while the remaining 10 MetS patients remained sedentary (E-group). The plasma concentrations of nitrite, cGMP, and ADMA (asymmetrical dimethylarginine; an endogenous nitric oxide synthase inhibitor), and the whole blood nitrite concentrations were determined at baseline and after exercise training using an ozone-based chemiluminescence assay, and commercial enzyme immunoassays. Thiobarbituric acid reactive species (TBA-RS) were measured in the plasma to assess oxidative stress using a fluorometric method. We found that, compared with healthy subjects, patients with MetS have lower concentrations of markers of NO formation, including whole blood nitrite, plasma nitrite, and plasma cGMP, and increased oxidative stress (all P<0.05). Exercise training increased the concentrations of whole blood nitrite and cGMP, and decreased both oxidative stress and the circulating concentrations of ADMA (both P<0.05). These findings show clinical evidence for lower endogenous NO formation in patients with MetS, and for improvements in NO formation associated with exercise training in MetS patients.

Topics: Adult; Arginine; Biomarkers; Cyclic GMP; Exercise Therapy; Humans; Lipid Peroxides; Metabolic Syndrome; Middle Aged; Nitric Oxide; Nitrites; Oxidative Stress; Thiobarbituric Acid Reactive Substances

The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear. We examined the effects of rosiglitazone on the plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and lipid profiles), markers of inflammation (high-sensitivity C-reactive protein [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between changes in endothelium-dependent flow-mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone. Of 70 nondiabetic patients who met a modified National Cholesterol Education Program definition of the metabolic syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to receive placebo for 8 weeks. At study end, treatment with rosiglitazone had significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (-16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and diastolic blood pressures. Rosiglitazone treatment significantly improved flow-mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001) of the right brachial artery. On multivariate analysis, changes in ADMA, endothelin-1, and CRP were independent predictors of improved endothelial reactivity with rosiglitazone. In conclusion, we have, for the first time, demonstrated the independent associations between the improvement in flow-mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome. These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as possible mechanisms for the improvement in endothelial function conferred by rosiglitazone treatment.

Topics: Arginine; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholesterol, HDL; Endothelin-1; Endothelium-Dependent Relaxing Factors; Female; Glucose; Humans; Insulin; Male; Metabolic Syndrome; Middle Aged; Regression Analysis; Rosiglitazone; Thiazolidinediones; Treatment Outcome; Vasodilator Agents

Circulating levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), are positively associated with the prevalence of metabolic syndrome (MetS) in cross-sectional investigations. It is unclear if circulating ADMA and other methylarginines are associated with incident MetS prospectively.. We related circulating ADMA, symmetric dimethylarginine (SDMA), L-arginine (ARG) concentrations (measured with a validated tandem mass spectrometry assay) and the ARG/ADMA ratio to MetS and its components in 2914 (cross-sectional analysis, logistic regression; mean age 58 years, 55% women) and 1656 (prospective analysis, Cox regression; mean age 56 years, 59% women) individuals from the Framingham Offspring Study who attended a routine examination.. Adjusting for age, sex, smoking, and eGFR, we observed significant associations of ADMA (direct) and ARG/ADMA (inverse) with odds of MetS (N = 1461 prevalent cases; Odds Ratio [OR] per SD increment 1.13, 95%CI 1.04-1.22; and 0.89, 95%CI 0.82-0.97 for ADMA and ARG/ADMA, respectively). Upon further adjustment for waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, and triglycerides, we observed a positive relation between SDMA and MetS (OR per SD increment 1.15, 95% CI 1.01-1.30) but the other associations were rendered statistically non-significant. We did not observe statistically significant associations between any of the methylarginines and the risk of new-onset MetS (752 incident events) over a median follow-up of 11 years.. It is unclear whether dimethylarginines play an important role in the incidence of cardiometabolic risk in the community, notwithstanding cross-sectional associations. Further studies of larger samples are needed to replicate our findings.

Topics: Arginine; Biomarkers; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Prevalence; Prospective Studies; Tandem Mass Spectrometry

PurposeThe aim of our study was to assess left ventricle and right ventricle systolic and diastolic functions in obese adolescents with metabolic syndrome using conventional echocardiography and pulsed-wave tissue Doppler imaging and to investigate carotis intima-media thickness, and asymmetric dimethyl arginine levels.. A total of 198 obese adolescents were enrolled in the study. The obese patients were divided into metabolic syndrome group and non-metabolic syndrome group. All subjects underwent laboratory blood tests, including asymmetric dimethyl arginine, complete two-dimensional, pulsed, and tissue Doppler echocardiography, and measurement of the carotid intima-media thickness.. Obese adolescents were characterised by enlarged left end-diastolic, end-systolic and left atrial diameters, thicker left and right ventricular walls compared with non-obese adolescents. The metabolic syndrome group had normal left ventricle systolic function, impaired diastolic function, and altered global systolic and diastolic myocardial performance. In the metabolic syndrome obese group patients, left ventricle mass was found positively correlated with body mass index, waist and hip circumferences, diastolic blood pressure, age, and waist-to-hip circumference ratio. The carotid intima-media thickness was found positively correlated with waist and hip circumferences and total cholesterol levels. Asymmetric dimethyl arginine levels were found positively correlated with systolic blood pressure, waist-to-hip circumference ratio, and diastolic blood pressure.. The results of this study demonstrate that metabolic syndrome in adolescence is associated with significant changes in myocardial geometry and function. In addition, it has been associated with a high level of asymmetric dimethyl arginine concentration and thicker carotid intima-media thickness reflecting endothelial dysfunction.

Topics: Adolescent; Arginine; Biomarkers; Carotid Intima-Media Thickness; Child; Diastole; Echocardiography, Doppler, Pulsed; Female; Follow-Up Studies; Heart Ventricles; Humans; Male; Metabolic Syndrome; Obesity; Retrospective Studies; Systole; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

Melatonin, a pineal hormone and a potent antioxidant, has important roles in metabolic regulation.. This study investigated serum asymmetric dimethylarginine (ADMA), homocysteine (Hcy), nitric oxide (NO) levels, known to be reliable markers of cardiovascular diseases, and determined possible protective effects of melatonin in fructose-fed rats.. Sprague-Dawley rats were divided into four groups: control, fructose, melatonin, and fructose plus melatonin. Metabolic syndrome was induced in rats by 20% (w/v) fructose solution in tap water, and melatonin was administered at the dose of 20 mg/kg bw per day by oral gavage. After 8 weeks, serum lipids, glucose, insulin, ADMA, Hcy, and NOx (the stable end products of NO) levels were quantified.. Fructose administration caused a statistically significant increase in systolic blood pressure (SBP), serum insulin, triglycerides, and very low-density lipoprotein (VLDL)-cholesterol levels compared with the control group and the metabolic syndrome model was successfully demonstrated. In comparison with the control group, fructose caused a significant increase in serum ADMA, Hcy, and NOx levels. Melatonin counteracted the changes in SBP, serum ADMA, and Hcy levels found in rats both alone and administered with fructose.. These results show that high fructose consumption leads to elevated SBP, atherogenic lipid profile, increased serum ADMA, and Hcy levels and melatonin treatment has beneficial effects on these biochemical parameters in rats. Melatonin might be beneficial for the prevention and/or treatment of the cardiovascular complications of metabolic syndrome not only by reducing the well-known risk factors of the disease but also by diminishing blood ADMA and Hcy levels.

Topics: Animals; Arginine; Biomarkers; Fructose; Homocysteine; Male; Melatonin; Metabolic Syndrome; Nitric Oxide; Rats; Rats, Sprague-Dawley; Treatment Outcome

We investigated the association of serum asymmetric dimethylarginine (ADMA) with metabolic syndrome (MetS), type-2 diabetes and coronary heart disease (CHD) in the general population.. Cross-sectional and, at 2000 person-years' follow-up, prospective analysis. Adults with measured serum ADMA level (n=848) were analyzed using tertiles or dichotomized values. ADMA concentrations were measured by a validated commercial ELISA kit.. Dichotomized subjects of combined sexes with low (≤0.68 µmol/L) ADMA values had significantly higher fasting glucose, total cholesterol, apolipoprotein B and lower diastolic blood pressure. In linear regression analyses comprising age, smoking, triglyceride, HDL-cholesterol, C-reactive protein and waist circumference as well, creatinine was significantly and independently associated with ADMA, further in women glucose (inversely). In logistic regression analyses uniformly adjusted for age, smoking status and waist girth, prevalent MetS tended to positive independent association with ADMA tertiles only in men. Combined prevalent and incident diabetes weakly tended to be associated with the lowest (vs mid- and highest) ADMA tertiles in combined gender; and prevalent and incident CHD was not associated with ADMA tertiles in either sex.. Apparently "low" circulating ADMA is independently associated with fasting glucose and tends to be so with type-2 diabetes. The lack of anticipated positive associations of ADMA with cardiometabolic disorders is likely due to autoimmune responses operating against serum ADMA under oxidative stress, rendering partial failure in immunoassay.

Topics: Adult; Anthropometry; Arginine; Biomarkers; Coronary Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Male; Metabolic Syndrome; Prospective Studies

Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis.

Topics: Adult; Aged; Arginine; Biomarkers; Blood Pressure; Case-Control Studies; Endothelium, Vascular; Female; Greece; Humans; Inflammation; Interleukin-6; Leukocytes, Mononuclear; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Telomerase; Tumor Necrosis Factor-alpha

The purpose of this study was to evaluate the potential associations between serum asymmetric dimethylarginine (ADMA) and several anthropometric, biochemical, and lifestyle features in healthy young adults, emphasizing on the putative effects of the antioxidant intake on ADMA concentrations. Anthropometric and blood pressure measurements as well as lifestyle features and antioxidant intake were analyzed in 93 healthy young adults aged 18 to 34 years. Fasting blood samples were collected for the measurement of glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerols, and ADMA concentrations, as well as erythrocyte glutathione peroxidase activity. Nail samples were collected for the analysis of selenium and zinc concentrations. Values of body mass index (P = .004), waist circumference (P = .008), waist-to-height ratio (P = .046), systolic blood pressure (P < .001), serum glucose (P < .001), and nail selenium (P = .004) and zinc (P = .018) were significantly different between subjects with serum ADMA higher and lower than the median (cutoff, 458 nmol/L). Furthermore, ADMA showed a positive association with several adiposity markers such as body weight (P < .001), body mass index (P < .001), waist circumference (P = .006), waist-to-height ratio (P = .020), body fat mass (P = .001), systolic blood pressure (P = .001), and serum glucose (P < .001), whereas erythrocyte glutathione peroxidase activity (P = .021) and nail selenium (P = .040) and zinc values (P = .013) were statistically significant negative predictors of ADMA concentrations. In conclusion, ADMA seems to be related with selenium and zinc status and several anthropometric and biochemical measurements linked to metabolic syndrome in apparently healthy young adults. These findings support a role for antioxidant/trace element intake in the modulation of ADMA, whose assessment may be a marker of metabolic syndrome manifestations.

Topics: Adiposity; Anthropometry; Antioxidants; Arginine; Blood Glucose; Blood Pressure; Body Composition; Diet; Erythrocytes; Female; Glutathione Peroxidase; Humans; Linear Models; Male; Metabolic Syndrome; Selenium; Young Adult; Zinc

We investigated serum asymmetric dimethylarginine (ADMA) levels and their association with smoking, metabolic syndrome (MS), and coronary heart disease (CHD) among Turkish adults.. Serum ADMA concentrations were measured in a cross-sectional study by a validated ELISA kit in a random sample of 464 Turkish adults (222 men, 242 women; mean age 55+/-11 years; range 34-89). Metabolic syndrome was identified by the criteria of the Adult Treatment Panel-III modified for male abdominal obesity.. The median serum ADMA concentration was 0.80 micromol/l, with the interquartile range of 0.57 to 1.13 micromol/l. Compared to nonsmokers, age-adjusted ADMA level was 20% lower in smoking men (p=0.057), and 6% lower in smoking women (p=0.6). Serum ADMA levels showed significant and positive correlations with age, testosterone, and fibrinogen concentrations in men, and a borderline significance with triglyceride, C-reactive protein, and sex hormone-binding globulin in women. No significant association was found with MS, hypertension, or CHD likelihood among men; but, after adjustment for age, smoking status, and systolic blood pressure, the odds ratio of doubling of ADMA for the likelihood of MS reached significance in women (OR 1.25; 95% CI 1.01; 1.53). Age- and smoking-adjusted ADMA in women tended to be associated also with hypertension (OR 2.55, p=0.07).. Serum ADMA levels are significantly associated with MS likelihood in women alone, but not with the likelihood for CHD in either gender. Serum ADMA in middle-aged and elderly Turks is inversely associated with cigarette smoking, and thus possibly contributes to the smoking-related protection of Turkish women from MS.

Topics: Adult; Aged; Aged, 80 and over; Arginine; Biomarkers; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Predictive Value of Tests; Prospective Studies; Risk Factors; Sex Factors; Smoking; Turkey; White People

Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. MATWERIALS AND METHODS: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-L-arginine (NMMA), lipids and body composition were measured.. Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75x in obese men and by 1.27x in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05).. Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.

Topics: Adult; Aged; Aged, 80 and over; Aging; Arginine; Blood Glucose; Body Composition; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; omega-N-Methylarginine; Proteins; Regression Analysis; Sex Characteristics

Topics: Albuminuria; Arginine; Cholesterol, HDL; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Foot; Hot Temperature; Humans; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Thrombomodulin; Vasodilation