dimethylarginine and Obesity

To determine whether postprandial metabolic and vascular responses induced by a high-fat and high-carbohydrate meal are attenuated by ingestion of the flavonol quercetin.. Twenty-two overweight-to-obese hypertensive patients participated in a randomized, double-blind, controlled, crossover meal study. They consumed a test meal (challenge) rich in energy (4754 kJ), fat (61.6 g), saturated fatty acids (53 % of total fatty acids), and carbohydrates (113.3 g) with either placebo or 54 mg quercetin. Blood pressure, reactive hyperemia index (RHI), high-sensitive C-reactive protein (hs-CRP), soluble endothelial-derived adhesion molecules, parameters of lipid and glucose metabolism, and markers of antioxidant status were measured before the meal and at 2 and 4 h postprandially.. Systolic and diastolic blood pressure increased significantly over time, but were not affected by treatment (placebo or quercetin). During both treatments, serum endothelin-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and plasma asymmetric dimethylarginine slightly decreased over time, whereas RHI increased. Serum triglycerides, total cholesterol, and insulin significantly increased, whereas HDL cholesterol and glucose significantly decreased over time, again with no effect of treatment. Plasma α-tocopherol significantly increased, and plasma Trolox equivalent antioxidative capacity decreased over time. Serum hs-CRP, plasma retinol, and β-carotene did not significantly change during the trial.. In hypertensive patients, a high-energy meal did not lead to postprandial impairment of vascular endothelial function. Postprandial metabolic responses induced by the challenge, such as lipemia and insulinemia, were not attenuated by the concomitant ingestion of quercetin.. This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00000555.

Topics: Adult; Aged; Arginine; beta Carotene; Blood Pressure; C-Reactive Protein; Cholesterol; Cross-Over Studies; Double-Blind Method; Endothelin-1; Female; Humans; Hypertension; Insulin; Intercellular Adhesion Molecule-1; Male; Middle Aged; Obesity; Onions; Overweight; Plant Extracts; Postprandial Period; Quercetin; Triglycerides; Vascular Cell Adhesion Molecule-1; Vitamin A

Hypertension is a major contributor to the global burden of cardiovascular diseases and its prevalence increases progressively with ageing. Therefore the identification of effective, age-friendly exercise and nutritional interventions which lower blood pressure (BP) is a research priority.. To undertake a pilot RCT examining the efficacy of isometric handgrip exercise (IHGE) and beetroot juice (a rich source of inorganic nitrate) consumption in modifying clinic and 24-h ambulatory BP (24-h ABP), peripheral arterial function and plasma asymmetric dimethylarginine (ADMA) in older overweight and obese adults.. Thirty middle age and older adults (62±5 years) were randomised to: (a) bilateral IHGE at 50% of maximal voluntary contraction (8 min/day), (b) 140 ml/day of concentrated beetroot juice, or (c) no-intervention (control group), for 7 days. All groups followed a standardised diet to control nitrate intake. Clinic and 24-h ABP, peripheral arterial function quantified by pulse wave velocity (PWV) and arterial volume distensibility were assessed before and after intervention.. Clinical ageing research unit, Newcastle University.. At baseline, there were no between-group differences in age, handgrip strength, clinic or 24-h ABP, BMI, waist circumference, fat mass, physical activity level, energy intake or urinary and plasma nitrate concentrations. After intervention, there were no significant effects on clinic systolic and diastolic BP or 24-h ABP, PWV (p=0.54), arterial volume distensibility (p=0.89), or ADMA (p=0.45).. IHGE or beetroot juice consumption for 7 days did not affect BP or peripheral arterial function in overweight and obese middle age and older adults. Ageing may reduce the effects of these interventions on vascular function and studies are needed to test this hypothesis.

Topics: Adult; Aged; Aging; Arginine; Beta vulgaris; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dietary Supplements; Exercise; Female; Hand Strength; Humans; Hypertension; Male; Middle Aged; Nitrates; Obesity; Overweight; Phytotherapy; Pulsatile Flow; Treatment Outcome

Plasma asymmetric dimethylarginine (ADMA) concentrations are higher in apparently healthy, insulin-resistant (IR) individuals and decrease in response to thiazolidenedione treatment.. The objective of the study was to determine whether ADMA concentrations would also fall when insulin sensitivity is enhanced with weight loss in obese individuals. DESIGN/SETTING/PATIENTS/INTERVENTION: Twenty obese women classified as IR or insulin sensitive (IS) on the basis of their steady-state plasma glucose (SSPG) concentration during the insulin suppression test underwent 12 wk of dietary weight loss.. Plasma glucose, insulin, and ADMA were measured at baseline and after weight loss; change in insulin resistance was quantified by repeating the SSPG after the dietary intervention.. Although weight loss was similar in the two groups, significant improvements in SSPG, glucose, and insulin concentrations were confined to the IR group. Baseline plasma ADMA concentrations (mean +/- sd) were higher in IR subjects (1.69 +/- 0.44 vs. 1.18 +/- 0.45 micromol/liter, P = 0.02) and decreased to 1.20 +/- 0.22 micromol/liter (P < 0.001) with weight loss. In contrast, ADMA levels did not change with a similar extent of weight loss in the IS group.. Plasma ADMA levels are higher in obese, IR women than in equally obese, IS women and decrease in response to weight loss when associated with enhancement of insulin sensitivity.

Topics: Adult; Arginine; Blood Glucose; Diet, Reducing; Female; Humans; Insulin; Insulin Resistance; Middle Aged; Obesity; Weight Loss

Nitric oxide (NO) is an important mediator involved in vascular homeostasis. Changes in NO level are considered to be associated with obesity and its clinical consequences. Previous studies on NO levels in obese children provided inconclusive results, so this issue requires clarification.. One of the main goals of this study was to assess whether childhood excessive body weight (EBW) is associated with changes in serum NO level and whether features like age and gender are linked to NO levels in selected groups.. In the present study, the serum NO levels were compared in 43 children with EBW and 37 ageand gender-matched children with normal weight. Moreover, in both groups, body measurements and various clinical parameters, including the serum concentrations of arginine (Arg), a precursor of NO, were determined.. The mean serum NO level in EBW group (8.7 ±3.1 μmol/L) was significantly lower than in normal weight group (22.2 ±11.5 μmol/L). However, the serum Arg concentrations were higher in EBW children than in controls. Serum asymmetric dimethylarginine (ADMA) levels were higher in EBW group and inversely correlated with serum NO. The EBW female subgroup was characterized by slightly lower level of NO than the EBW male subgroup. There were no significant changes in serum NO level among different age subgroups in both groups.. Our results revealed that EBW in children is associated with significantly decreased level of serum NO. The decreased serum NO level in EBW children is not a result of depleted Arg in the blood. Asymmetric dimethylarginine may at least partially contribute to decreased NO levels in children with EBW. A decreased level of NO could be a potential early marker of the risk of cardiovascular disorders developing in children with EBW.

Topics: Adolescent; Arginine; Biomarkers; Body Weight; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Female; Humans; Male; Nitric Oxide; Obesity

Asymmetric dimethylarginine (ADMA) plays a vital role in the regulation of insulin sensitivity and has been shown as a potential marker for various disease, including type 2 diabetes mellitus (DM2). However, the correlation between ADMA and impaired glucose tolerance (IGT) and obesity has not been studied. A total of 195 subjects were involved in our study. The characteristics of the subjects in the study cohort were measured and analyzed. We found that the serum ADMA and C-reactive protein levels were significantly increased in IGT and diabetic patients, whereas the levels of lipoprotein A and adiponectin were decreased, especially in diabetic patients with obesity. The serum ADMA level was positively correlated to a homeostatic model assessment for insulin resistance, and multivariate regression analysis further indicated that ADMA was an independent factor for DM patients with obesity. Our study expands the understanding of the complicated relationship between obesity, insulin resistance, IGT, and ADMA. In addition, we demonstrated that the serum ADMA level could serve as a diagnositic biomarker of the early signs for IGT patients with obesity.

Topics: Aged; Arginine; Biomarkers; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Obesity

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

In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx).. We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results.. At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85. Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.

Topics: Apolipoproteins; Arginine; Biomarkers; Body Mass Index; Case-Control Studies; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Insulin Resistance; Lipids; Liver Transplantation; Male; Obesity; Oxidative Stress; Triglycerides

Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-α (TNF-α), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-α mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-α, and ADMA in the plasma, liver, or brain.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Arginine; Dexamethasone; Diet, High-Fat; Female; Inflammation; Insulin-Like Growth Factor I; Liver; Male; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; RNA, Messenger; Sensation Disorders; Space Perception; Tumor Necrosis Factor-alpha

Obesity is a major risk factor for many chronic metabolic diseases such as inflammation, insulin resistance (IR) and fatty liver injury. It was reported that obesity causes some variations on the serum levels of fetuin-A and is associated with arginine metabolism, especially arginase-1 levels. The aim of our study was to evaluate, the interaction and possible changes of these liver over produced proteins, fetuin-A and arginase-1 levels in obesity-related inflammatory status. Study groups were composed of individuals aged between 19 and 63 (n = 62). The control group included healthy subjects with BMI < 25, obese group included obese patients with BMI > 30 and with no other chronic disease. Biochemical markers were determined by an auto-analyzer. Adiponectin, fetuin-A, arginase-1, asymmetric dimethylarginine (ADMA), arginine, Hexanoyl-lysine (HEL) and leptin levels were measured with commercial ELISA immunoassay kits. Nitrite and nitrate were determined with colorimetric assay kit in serum samples. High sensitive C-reactive protein (hsCRP) levels and liver function enzymes activities were higher in the obese group in respect to the control group. Serum fetuin-A, arginase-1 and leptin levels were increased but adiponectin levels were decreased in obese subjects. Fetuin-A levels showed significant correlations with arginase-1 and HOMA-IR. Consequently, we carried out an investigation about higher serum fetuin-A and arginase-1 levels may have an important role in obesity and obesity-related liver damage.

Topics: Adiponectin; Adult; alpha-2-HS-Glycoprotein; Arginase; Arginine; Biomarkers; C-Reactive Protein; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Linear Models; Liver Function Tests; Lysine; Male; Middle Aged; Nitrates; Nitrites; Obesity

Intermittent claudication is a form of exercise intolerance characterized by muscle pain during walking in patients with peripheral artery disease (PAD). Endothelial cell and muscle dysfunction are thought to be important contributors to the etiology of this disease, but a lack of preclinical models that incorporate these elements and measure exercise performance as a primary end point has slowed progress in finding new treatment options for these patients. We sought to develop an animal model of peripheral vascular insufficiency in which microvascular dysfunction and exercise intolerance were defining features. We further set out to determine if pharmacological activation of 5'-AMP-activated protein kinase (AMPK) might counteract any of these functional deficits. Mice aged on a high-fat diet demonstrate many functional and molecular characteristics of PAD, including the sequential development of peripheral vascular insufficiency, increased muscle fatigability, and progressive exercise intolerance. These changes occur gradually and are associated with alterations in nitric oxide bioavailability. Treatment of animals with an AMPK activator, R118, increased voluntary wheel running activity, decreased muscle fatigability, and prevented the progressive decrease in treadmill exercise capacity. These functional performance benefits were accompanied by improved mitochondrial function, the normalization of perfusion in exercising muscle, increased nitric oxide bioavailability, and decreased circulating levels of the endogenous endothelial nitric oxide synthase inhibitor asymmetric dimethylarginine. These data suggest that aged, obese mice represent a novel model for studying exercise intolerance associated with peripheral vascular insufficiency, and pharmacological activation of AMPK may be a suitable treatment for intermittent claudication associated with PAD.

Topics: Aging; AMP-Activated Protein Kinases; Animals; Apolipoproteins E; Arginine; Cilostazol; Diet, High-Fat; Disease Models, Animal; Enzyme Activation; Enzyme Activators; Humans; Intermittent Claudication; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle Fatigue; Muscle, Skeletal; Nitric Oxide Synthase Type III; Obesity; Peripheral Vascular Diseases; Phosphodiesterase 3 Inhibitors; Physical Exertion; Tetrazoles; Vasodilator Agents

To define the clinical significance of asymmetric dimethylarginine (ADMA) and that of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism as factors of endothelial dysfunction (ED) in the development of early kidney injury in obese patients.. The investigation included 86 patients (64 men and 22 women aged 44 +/- 11 years) with abdominal obesity. Along with physical examination, the authors determined albuminuria, calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula, estimated insulin resistance markers (fasting plasma insulin and C-peptide concentrations and homeostatic model assessment (HOMA) index), as well as serum ADMA levels by enzyme immunoassay in all the patients. C677T polymorphism in the MTHFR gene was studied by allele-specific polymerase chain reaction and restriction fragment length polymorphism analysis. Kidney injury (chronic kidney disease (CKD)) was diagnosed using the Kidney Disease Outcomes Quality Initiative (KDOQI) criteria. Early vascular remodeling was determined from the increased intima-media thickness (IMT) of the common carotid artery (CCA).. CKD was diagnosed in 27(31%) patients. The latter, unlike the patients with CKD, were observed to have more pronounced obesity (body mass index (BMI) 36.8 +/- 8.0 and 32.0 +/- 4.7 kg/m2, respectively (p < 0.001)), waist circumference (119 +/- 18 and 109 +/- 11 cm (p = 0.002)), higher levels of C-peptide (1348 +/- 363 and 1028 +/- 363 pmol/I; p < 0.001), insulin (16.9 +/- 7.3 and 11.7 +/- 5.5 microU/ ml; p < 0.001), and HOMA index (4.3 +/- 1.7 and 2.9 +/- 1.5; p < 0.001). In the patients with Stage IIIa CKD, ADMA concentrations (0.77 +/- 0.19 micromol/l) was higher than in those with Stages I (0.58 +/- 0.11 micromol/l; p = 0.048) and II (0.61 +/- 0.13 micromol/l; p = 0.071). An association between ADMA concentrations, CCA IMT, and estimated GFR was revealed in the patients with CKD. The predictors of an estimated GFR reduction in obesity were elevated serum concentrations of ADMA, uric acid, insulin, and HOMA index. The combination of obstructive sleep apnea syndrome and metabolic syndrome increased the risk of CKD by 2.1-fold (95% confidence interval, 1.06-3.14). Evaluation of the impact of MTHFR gene polymorphism on kidney injury in obesity disclosed that the patients with homozygous carriage of the abnormal T allele of the MTHFR gene had a higher risk for Stages I-IIIa CKD (2.60 with 95% confidence interval, 1.32-3.88), more marked obesity and hyperinsulinemia, and increased serum ADMA concentrations.. Insulin resistance and ED hold a central position in the pathogenesis of CKD in obese patients. The mechanisms of the atherosclerotic vascular remodeling associated with elevated serum ADMA concentrations are of paramount importance in the progression of early-stage CKD. The homozygous carriage of the abnormal T allele of the MTHFR gene increases the risk of Stages I-IIIa by more than twice.

Topics: Adult; Arginine; Carotid Artery, Common; Data Interpretation, Statistical; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Hypoxia; Insulin Resistance; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Obesity; Polymorphism, Genetic; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Tunica Media; Ultrasonography

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 μg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 μmol/L; P < .01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.

Topics: Adiponectin; Adipose Tissue; Arginine; Chemokine CCL2; Humans; Immunosuppressive Agents; Kidney Transplantation; Leptin; Muscles; Nicotinamide Phosphoribosyltransferase; Obesity; Peritoneal Dialysis; Prospective Studies; Renal Dialysis; Tumor Necrosis Factor-alpha

Topics: Arginine; Carotid Arteries; Female; Humans; Hyperhomocysteinemia; Obesity; Polycystic Ovary Syndrome; Reference Values; Tunica Intima; Tunica Media

We have assessed in obese renal transplant recipients a course of selected proinflammatory factors liable to influence the long-term outcome of transplant patients and kidney grafts.. In a prospective cohort study, we examined a total of 68 obese renal transplant recipients (body mass index [BMI] >or= 30 kg/m(2)) for a period of 12 months (Group I). A control group consisted of 72 comparable non-obese renal transplant recipients (Group II).. Significant differences were found in plasma 12 months after renal transplantation (Group I versus Group II) in asymmetric dimethylarginine (ADMA; 3.68 micromol/L +/- 0.42 micromol/L vs 2.10 micromol/L +/- 0.34 micromol/L; P < .01), adiponectin (ADPN; 15.1 microg/mL +/- 6.0 microg/mL vs 22.80 microg/mL +/- 7.2 microg/mL; P < .01), leptin (50.4 ng/L +/- 10.2 ng/L vs 22.0 ng/L +/- 8.4 ng/L; P < .01), solubile leptin receptor (ObRe; 23.6 U/mL +/- 7.4 U/mL vs 47.2 U/mL +/- 10.7 U/mL; P < .01), resistin (21.2 microg/mL +/- 10.2 microg/mL vs 15.0 microg/mL +/- 6.2 microg/mL; P < .025) and triglycerides (3.9 mmol/L +/- 1.6 mmol/L vs 2.8 mmol/L +/- 1.6 mmol/L; P < .01). There were significant correlations between ADMA and BMI (r = 0.525, P < .001), ADPN and BMI (r = -0.574, P < .001), and ADMA and ADPN in visceral fat (r = -0.510, P < .001). Correlation between ADMA and Cin was weak, but significant (r = -0.190, P < .05).. The results indicate that obesity after renal transplantation was associated with increased plasma ADMA and decreased ADPN in plasma and in fat tissue and may represent a risk factor for renal transplant recipients.

Topics: Adiponectin; Adult; Aged; Arginine; Body Mass Index; Case-Control Studies; Cohort Studies; Female; Humans; Kidney Transplantation; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Receptors, Leptin; Resistin; Risk Factors; Triglycerides

In obese renal transplant recipients, we assessed the course of selected proinflammatory factors liable to influence long-term outcomes of transplant patients and kidney grafts.. In a prospective cohort study, we examined a total of 140 renal transplant recipients for a period of 12 months. Based on body mass index (BMI), patients were divided into Group I (BMI > or = 30 kg/m2, 68 patients) and Group II (BMI < or = 30 kg/m2, 72 patients).. Twelve months after renal transplantation, significant differences were found between Group I versus Group II in plasma levels of asymmetric dimethylarginine (ADMA) (3.65 [SD +/- 0.47 micromol/L] versus 2.01 [SD +/- 0.36 micromol/L], P < .01), adiponectin (ADPN) (15.4 [SD +/- 6.6 microg/mL] versus 22.3 [SD +/- 8.2 microg/mL], P < .01), leptin (51.3 [SD +/- 11.2 ng/L] versus 21.3 [SD +/- 9.2 ng/L], P < .01), soluble leptin receptor (24.6 [SD +/- 8.4 U/mL] versus 46.1 [SD +/- 11.4 U/mL], P < .01), resistin (20.8 [SD +/- 10.1 microg/mL] versus 14.6 [SD +/- 6.4 microg/mL], P < .025), and triglycerides (3.9 [SD +/- 1.6] versus mmol/L 2.8 [SD +/- 1.6 mmol/L], P < .01). There were significant correlations between ADMA and BMI (r = 0.520; P < .001), and ADPN and BMI (r = -0.570, P < .001). The correlation between ADMA and inulin clearance (Cin) was weak (r = -0.185, P < .05).. Obesity after renal transplantation is associated with increased ADMA and decreased ADPN in plasma, and this may represent a risk factor for renal transplant recipients.

Topics: Adiponectin; Adult; Aged; Arginine; Body Mass Index; Cohort Studies; Female; Humans; Kidney Transplantation; Male; Middle Aged; Obesity; Prospective Studies

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