osteoprotegerin and Metabolic-Syndrome

Osteoprotegerin (OPG) is a member of the tumour necrosis factor receptor superfamily of cytokines which, in spite of being initially described as a strong anti-resorptive factor, has lately been considered as a possible link between bone and vascular disease. In the last few years, several studies have evidenced its close relationship with the development of diabetes. In this review, we analyse the role of OPG in diabetic patients and its links with the most relevant associated diseases such as atherosclerosis, hypertension, endothelial dysfunction and diabetic nephropathy, as well as its connection with related pathologies as fibrosis, obesity and metabolic syndrome.

Topics: Atherosclerosis; Diabetes Complications; Diabetic Nephropathies; Fibrosis; Humans; Hypertension; Metabolic Syndrome; Obesity; Osteoprotegerin

The mortality rate is extremely high in chronic kidney disease (CKD), primarily due to the high prevalence of cardiovascular disease (CVD) in this patient group. Apart from traditional Framingham risk factors, evidences suggest that nontraditional risk factors, such as inflammation, oxidative stress, endothelial dysfunction, and vascular calcification also contribute to this extremely high risk of CVD. Disturbance in the mineral metabolism, especially in the ions of Ca and PO4, are linked to enhanced calcification of blood vessels. Although the mechanism(s) of this enhanced calcification process are not fully understood, current knowledge suggests that a large number (and an imbalance between them) of circulating promoters and inhibitors of the calcification process, that is, fetuin-A (or alpha 2-Heremans-Schmid glycoprotein, AHSG), matrix-Gla protein (MGP), osteoprotegerin (OPG), osteopontin (OPN), bone morphogenetic proteins (BMPs), and inorganic pyrophosphate (PPi), are involved in the deterioration of vascular tissue. Thus, an imbalance in these factors may contribute to the high prevalence of vascular complications in CKD patients. Among these mediators, studies on fetuin-A deserve further attention as clinical studies consistently show that fetuin-A deficiency is associated with vascular calcification, all-cause and cardiovascular mortality in CKD patients. Both chronic inflammation and the uremic milieu per se may contribute to fetuin-A depletion, as well as specific mutations in the AHSG gene. Recent experimental and clinical studies also suggest an intriguing link between fetuin-A, insulin resistance, and the metabolic syndrome.

Topics: alpha-2-HS-Glycoprotein; Blood Proteins; Bone Morphogenetic Protein 7; Calcinosis; Calcium-Binding Proteins; Cardiovascular Diseases; Chronic Disease; Extracellular Matrix Proteins; Humans; Inflammation; Kidney Diseases; Matrix Gla Protein; Metabolic Syndrome; Osteopontin; Osteoprotegerin; Vascular Diseases

Osteoprotegerin (OPG), a member of the tumour necrosis factor receptor (TNFR) superfamily of proteins known to be involved in a large number of biological systems, plays a pivotal role in bone remodelling. In addition to the roles of OPG in bone metabolism, it has been reported to be associated with a high cardiovascular risk in patients with metabolic syndrome. In most cases, the exact functions of OPG remain to be established; however, the widespread expression of OPG suggests that this molecule may have multiple biological activities, mainly in the cardiometabolic environment. The aim of this study was to evaluate the value of OPG as a predictive marker for cardiovascular and metabolic risk in osteoporotic patients. The study group comprised patients with osteoporosis, in order to evaluate the association between OPG serum levels and cardiovascular pathology. Our results revealed significant correlations between classical biochemical bone and metabolic parameters, such as osteocalcin and parathyroid hormone with lipid and glucose biomarkers, sustaining the crosstalk between calcium and bone parameters and cardiovascular risk. The OPG serum level proved to have a significant and independent predictive value for metabolic syndrome (MetS) as a cardiovascular risk standard in osteoporotic patients. The OPG serum levels were increased in patients with MetS as a protective response against the atherosclerotic lesions. The serum levels of 25‑hydroxy vitamin D had significant and independent predictive value for cardiovascular and metabolic risk in our subjects, sustaining the active role of vitamin D beyond the area of bone metabolism.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bone Remodeling; Cardiovascular Diseases; Female; Glucose; Humans; Lipids; Metabolic Syndrome; Middle Aged; Osteocalcin; Osteoporosis; Osteoprotegerin; Parathyroid Hormone; Risk Assessment; Risk Factors; Vitamin D; Young Adult

Our aim was to determine whether 12 weeks' aerobic Nordic walking (NW) or resistance exercise training (RT) without diet-induced weight loss could decrease oxidative stress and atherogenic index of plasma (AIP), prevalence of metabolic syndrome (MetS) and MetS score in middle-aged men with impaired glucose regulation (IGR) (n=144. 54.5 ± 6.5 years). In addition, we compared effects of intervention between overweight and obese subgroups. Prevalence of MetS and AIP index decreased only in NW group and MetS score in both NW and RT groups but not in control group. The changes in AIP index correlated inversely with changes in plasma antioxidant capacity. The change in AIP index remained a significant independent predictor of the changes in MetS score after the model was adjusted for age, BMI and volume of exercise (MET h/week) in NW group. There were no changes in the other measured markers of oxidative stress and related cytokines (e.g. osteopontin and osteoprotegerin) in any of the groups. Nordic walking decreased prevalence of MetS and MetS score. Improved lipid profile remained a predictor of decreased MetS score only in NW group and it seems that Nordic walking has more beneficial effects on cardiovascular disease risks than RT training.

Topics: Adult; Aged; Antioxidants; Atherosclerosis; Body Mass Index; Diet; Exercise; Glucose; Humans; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Osteopontin; Osteoprotegerin; Overweight; Oxidative Stress; Resistance Training; Walking

Chronic inflammation has been identified as an important component of metabolic syndrome (MetS). Inhibition of the inflammatory mediator signals is a promising strategy against insulin resistance, atherosclerosis and other problems associated with MetS. Regular exercise decreases the components associated with MetS, including inflammatory cytokines. However, the relationship between an acute resistance training (RT) session, cytokine levels and MetS is unclear. Therefore, the aim was to evaluate the effects of a single bout of acute RT on tumour necrosis factor (TNF-α), interleukins (IL) IL-1a, IL-1β, IL-12, IL-6, IL-10 and osteoprotegerin (OPG) in women with MetS. Twenty-four women were divided into 2 groups: metabolic syndrome (MetS) and non-metabolic syndrome (Non-MetS). After the familiarization and testing for 1 repetition maximum (1RM), participants completed 3 sets of 10 repetitions in the following exercises: machine leg press, leg extension, leg curl, chest press, lat front pull-down and machine shoulder press with 60% of 1RM followed by 15 repetitions of abdominal crunches. A rest interval of 1 min was allowed between sets and exercises. Plasma TNF-α, IL-1a, IL-1β, IL-12, IL-6, IL-10 and OPG were measured before, immediately post and 60 min after RT. MetS group showed significantly higher concentrations of IL-1β (P = 0·024) and IL-6 (P = 0·049) and a trend for higher TNF-α values (P = 0·092) compared with Non-MetS. There was no group × time interactions after the RT session on the measured cytokines and osteoprotegerin. In conclusion, acute RT session induced no additional increase in pro-inflammatory cytokines nor a decrease in anti-inflammatory cytokines and OPG in women with MetS.

Topics: Adult; Biomarkers; Brazil; Cytokines; Female; Humans; Inflammation Mediators; Metabolic Syndrome; Osteoprotegerin; Resistance Training; Time Factors; Treatment Outcome

This study evaluated the effects of Bifidobacterium animalis subsp. lactis HN019 (B. lactis HN019) in the development of periodontitis (PE), associated or not with metabolic syndrome, (MS) in rats.. Ninety-six rats were grouped according to a food protocol: high-fat diet for induction of MS or standard diet for the control groups (C). They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) probiotic (PROB): C-**, CP-*, PE+**, PEP+*, MS- MSP-*, MSPE+**, and MSPEP+*. PROB administration started on the eighth week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular analyzes, immunoenzymatic assays, and microtomographic analyses were performed. The data obtained were analyzed statistically (P < 0.05).. The PEP and MSPEP groups showed lower levels of alveolar bone loss when compared with the PE and MSPE groups, respectively (P < 0.05). The immunoenzymatic analysis showed higher levels of interleukin (IL)-1β and a higher receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio in the MSPE group when compared with the MSPEP group (P < 0.05). The PEP group showed lower levels of tumor necrosis factor (TNF)-α and IL-6 when compared with the PE group. The use of PROB attenuated dyslipidemia parameters in animals with MS, with or without PE.. B. lactis HN019 reduced more significantly the severity of PE in rats with MS, modulating both systemic metabolic and immunoinflammatory parameters in periodontal tissues.

Topics: Alveolar Bone Loss; Animals; Bifidobacterium animalis; Metabolic Syndrome; Osteoprotegerin; Periodontitis; Probiotics; RANK Ligand; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Topics: Animals; Bixaceae; Bone Morphogenetic Proteins; Carotenoids; Disease Models, Animal; Fibroblast Growth Factors; Genetic Markers; Intercellular Signaling Peptides and Proteins; Male; Metabolic Syndrome; Osteocytes; Osteoporosis; Osteoprotegerin; Parathyroid Hormone; Plant Extracts; RANK Ligand; Rats, Wistar; Tibia; Tocotrienols

Inflammation plays a major role in the development of metabolic syndrome (MetS) and its progression. Recent studies have shown that pentraxin-3 (PTX-3), osteoprogerin (OPG), and tumor necrosis factor-alpha (TNF-α) are key factors in MetS pathophysiology, but evidence for endorsing their clinical use is currently unclear and insufficient.. The study aimed to evaluate the association between the inflammatory biomarkers' levels and the severity of MetS.. The study was observational, transversal, prospective, cohort, and analytical type. We enrolled 80 patients (M:F = 1, mean age = 55 ± 10.77 years) who met MetS criteria. The study protocol included: medical history, physical examination, 6-min walk test distance (6MWTD), biochemical tests, electrocardiogram, echocardiography, and carotid ultrasonography. We also performed plasmatic measurement of PTX-3, OPG, and TNF-α, in addition to standard biochemical tests.. PTX-3 was correlated with the severity of MetS, with other inflammatory parameters and cardiovascular tests. CCA-IMT and 6MWTD are useful in differentiating between mild and severe MetS.

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Serum Amyloid P-Component; Tumor Necrosis Factor-alpha; Waist Circumference

Osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC) are matrix glycoproteins which mediate bone mineralization; moreover, their effects on glucose/insulin homeostasis have recently been demonstrated. Higher circulating OPN and OPG levels have been associated with the presence of insulin resistance, atherosclerosis and coronary heart disease. No data are available on contextual changes of these markers in type 2 diabetes mellitus (T2DM). Therefore, aims of this study were to evaluate serum OPN, OPG and OC levels in T2DM patients and their clinical correlates.. We recruited 83 consecutive T2DM patients referring to our diabetes outpatient clinics at Sapienza, University of Rome, and 71 non-diabetic sex and age-comparable subjects as a control group. Study population underwent metabolic characterization and carotid ultrasound for intima-media thickness measurement. Plasma OPN, OPG and OC were measured by MILLIPLEX Multiplex Assays Luminex.. T2DM patients had significantly higher circulating OPN and OPG levels than controls (14.3 ± 13.6 vs 10.6 ± 13.7 ng/ml p < 0.001, 0.70 ± 0.60 vs 0.54 ± 4.1 ng/ml, p = 0.02) while OC levels were similar in the two cohorts (6.35 ± 5.8 vs 7.80 ± 7.0 ng/ml, p = n.s). OPN and OPG positively correlated with greater systolic blood pressure (SBP) values, HOMA-IR and HOMA-β, and with the presence of dyslipidemia and carotid atherosclerosis. The association between greater OPN and OPG levels and SBP was independent from possible confounders (both p = 0.01).. Circulating OPN and OPG levels are increased in T2DM patients and identify a particularly unfavourable metabolic profile, mostly expressed by higher SBP. Bone peptides may represent novel markers of vascular stress and accelerated atherosclerosis in diabetes, constituting a possible tool for cardiovascular risk stratification in diabetes.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Metabolome; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Prognosis; Risk Factors

BACKGROUND Osteoprotegerin (OPG) is a soluble glycoprotein that belongs to the tumor necrosis factor (TNF) receptor superfamily. OPG is mainly secreted by bone. The relationship between acute resistance training, serum OPG levels and metabolic syndrome, including insulin resistance, remains unclear. The purpose of this study was to determine the effect of resistance exercise on serum OPG levels and insulin resistance in middle-aged women with metabolic syndrome. MATERIAL AND METHODS Twenty-four middle-aged women were divided into those with metabolic syndrome (n=12) and a normal control group without metabolic syndrome or insulin resistance (n=12). Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The quantitative insulin-sensitivity check index (QUICKI) and the homeostatic model assessment (HOMA) index for assessing beta-cell function and insulin resistance were used. The intensity of the resistance exercise was 60-70% of the repetition maximum, for 40 minutes with 10-12 repetitions, performed three times per week. Venous blood samples were tested using standard laboratory procedures. RESULTS Before exercise, the metabolic syndrome group showed a significant increase in waist circumference (P=0.030) and serum triglyceride (TG) (P=0.014), and lower high-density lipoprotein-cholesterol (HDL-C) (P=0.010) compared with the control group. After the eight-week resistance exercise program, waist circumference, and the QUICKI decreased and OPG levels were significantly increased in the metabolic syndrome group compared with the normal control group. CONCLUSIONS A resistance exercise program was effective in reducing factors associated with metabolic syndrome including insulin resistance and increases serum levels of OPG in middle-aged women.

Topics: Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Exercise; Exercise Therapy; Female; Humans; Insulin Resistance; Metabolic Syndrome; Middle Aged; Obesity; Osteoprotegerin; Resistance Training; Triglycerides; Waist Circumference

To evaluate osteoprotegerin serum concentration (and compare with healthy controls), to estimate the relationship between serum osteoprotegerin and lipid parameters, insulin resistance, and selected inflammatory factors, and to assess the relationship between osteoprotegerin and intima media thickness in patients with metabolic syndrome.. A total of 70 individuals aged 18-65 years with metabolic syndrome were enrolled. Anthropometric parameters, including body weight, body mass index, waist circumference, and waist-hip ratio, were assessed. The relative and absolute fat tissue contents were evaluated. Serum glucose, insulin, osteoprotegerin, C-reactive protein, and lipid profile were determined. Insulin resistance was calculated using Homeostasis Model Assessment. Intima media complex thickness was evaluated in each participant.. No significant differences were observed between patients and the controls with respect to lipid and carbohydrate profiles. Osteoprotegerin was significantly elevated in metabolic syndrome patients compared to the controls. Both C-reactive protein serum concentration and insulin resistance increased in the metabolic syndrome patients. Significant positive correlations between osteoprotegerin serum concentration and body mass index, waist-hip ratio, C-reactive protein serum concentration, and insulin resistance, were documented in patients with metabolic syndrome.. Patients with metabolic syndrome have increased osteoprotegerin serum levels than healthy individuals. Osteoprotegerin plays an important role in the development of arteriosclerosis, and the effect of osteoprotegerin on intima media thickness strongly depends on the extent of the arteriosclerotic changes that occur in metabolic syndrome.

Topics: Adolescent; Adult; Aged; Atherosclerosis; Body Mass Index; C-Reactive Protein; Carotid Intima-Media Thickness; Case-Control Studies; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Risk Factors; Waist Circumference; Waist-Hip Ratio; Young Adult

This study aimed to determine the association between visceral adipose tissue (VAT), liver fat (LF) content, and other markers of the metabolic syndrome (MetS) and osteoprotegerin (OPG) in dysmetabolic adults.. Subjects from the NUMEVOX cohort were included if they fulfilled at least one MetS criterion. They then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (HOMA-IR) indices and OPG. VAT and LF content were measured by magnetic resonance imaging (MRI). Ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated.. Body mass index, waist circumference and MRI-derived VAT correlated with OPG, whereas abdominal subcutaneous fat did not. OPG levels were strongly correlated with LF content (r=0.25, P=0.003), liver markers such as alanine aminotransferase (r=0.39, P<0.001) and HOMA-IR index (r=0.39, P<0.0001). Plasma OPG also correlated with arterial stiffness and the number of atherosclerotic sites.. Plasma OPG levels are positively associated with both liver markers and increased LF content, but not with subcutaneous fat in dysmetabolic men. These findings suggest that elevated OPG levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk.

Topics: Adult; Biomarkers; Body Mass Index; Cohort Studies; Fatty Liver; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Liver; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin

The aim of the present study was to evaluate value of osteoprotegerin (OPG) in patients with degenerative aortic stenosis and preserved left-ventricular ejection fraction.. We have prospectively followed 70 patients with aortic stenosis (mean aortic gradient ≥15 mmHg) and preserved left-ventricular ejection fraction for 1 year. In all patients, echocardiography and blood tests (OPG, lipids, high-sensitivity C-reactive protein) were performed at baseline and after 1 year of follow-up. Detailed medical history including atherosclerotic risk factors was obtained. The control group consisted of 20 healthy individuals with normal echocardiographic findings. Rapid progression of aortic stenosis was defined as more than 7 mmHg increase in mean aortic gradient per year.. Osteoprotegerin concentrations were significantly higher in patients with aortic stenosis (P < 0.0001) and correlated with the degree of aortic stenosis. In multivariable regression model analysis, age (β = 0.015, P < 0.0001), mean aortic gradient (β = 0.04, P = 0.0078) and presence of coronary artery disease (β = 0.111, P = 0.0408) were the only independent determinants of plasma OPG concentrations. There was no association between OPG concentrations and coronary artery disease risk factors: male sex, smoking, hypertension and hypercholesterolemia. Concentrations of high-sensitivity C-reactive protein correlated positively with OPG levels only in nonsurgical patients (with lower degree of stenosis) (r = 0.34, P = 0.01). Aortic stenosis progression was related to body mass, diabetes, triglyceride concentrations, metabolic syndrome and left-ventricular systolic volume. In multivariate analysis, only metabolic syndrome was an independent predictor of aortic stenosis progression.. Osteoprotegerin concentrations are linked to the presence and severity of aortic stenosis. Metabolic syndrome was the only independent predictor of degenerative aortic stenosis progression.

Topics: Aged; Aortic Valve Stenosis; Biomarkers; C-Reactive Protein; Disease Progression; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Prognosis; Prospective Studies; Severity of Illness Index; Stroke Volume; Ventricular Function, Left

Osteoprotegerin (OPG) is a cytokine that regulates bone resorption by inhibiting osteoclastogenesis, and OPG has been implicated in the process that causes vascular stiffness. An increase in serum OPG level has been associated with the development of arterial stiffness. Kidney transplant (KT) patients are susceptible to aortic stiffness, which is considered to be a predictor of cardiovascular events in this patient population. Carotid-femoral pulse wave velocity (cfPWV) has emerged as a gold standard for non-invasive evaluation of aortic stiffness. The aim of this study was to evaluate the relationship between serum OPG concentration and cfPWV among KT patients. Fasting blood samples were obtained from 57 KT patients and their cfPWV was measured using applanation tonometry. The serum OPG levels were measured using an enzyme-linked immunosorbent assay. Univariable linear regression analysis showed that the cfPWV in KT patients was significantly and positively correlated with age, body weight, waist circumference, body mass index, log-creatinine, systolic blood pressure, diastolic blood pressure, pulse pressure, and the log-OPG concentration. KT patients with metabolic syndrome had higher cfPWV values than those without metabolic syndrome (P = 0.036), which indicates a higher incidence of aortic stiffness in this patient population. Multivariable forward stepwise linear regression analysis of the significant variables showed that the log-OPG (P = 0.001), the log-creatinine (P = 0.004), and the SBP (P = 0.005) remained as independent and positive predictors of cfPWV values. These findings indicate that serum OPG levels are positively associated with cfPWV in KT patients.

Topics: Age Factors; Blood Pressure; Body Mass Index; Body Weight; Creatinine; Enzyme-Linked Immunosorbent Assay; Humans; Kidney Transplantation; Linear Models; Manometry; Metabolic Syndrome; Osteoprotegerin; Pulse Wave Analysis; Vascular Stiffness

Inflammation is believed to link obesity to insulin resistance, as in the setting of metabolic syndrome (MetS). Osteoprotegerin (OPG) is a soluble protein that seems to exert proatherogenic and prodiabetogenic effects. This study aims at determining OPG levels in MetS and whether OPG might contribute to MetS development and progression.. Circulating OPG was measured in 46 patients with MetS and 63 controls, and was found significantly elevated in those with MetS. In addition, circulating and tissue OPG was significantly increased in high-fat diet (HFD) fed C57BL6 mice, which is one of the animal models for the study of MetS. To evaluate the consequences of OPG elevation, we delivered this protein to C57BL6 mice, finding that it promoted systemic and adipose tissue proinflammatory changes in association with metabolic abnormalities.. These data suggest that OPG may trigger adipose tissue proinflammatory changes in MetS/HFD-induced obesity.

Topics: Adipose Tissue; Adult; Animals; Blood Glucose; Body Mass Index; C-Reactive Protein; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Female; Humans; Inflammation; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Middle Aged; Obesity; Osteoprotegerin; Triglycerides

Osteoprotegerin (OPG) is a glycoprotein from tumour necrosis factor receptor superfamily, responsible for osteoclastogenesis inhibition and associated with arterial calcification and stiffness. We describe the association between metabolic syndrome (MS) and OPG in type 2 diabetes mellitus patients.. We consecutively enrolled 1220 patients from our institution's Diabetes Centre from August 2011. Anthropometric data such as fasting blood/urine were obtained, and OPG was measured by enzyme-linked immunosorbent assay (ELISA).. Mean (standard deviation (SD)) of age and diabetes duration was 57.4 (10.9) years and 11.2 (8.9) years, respectively. Prevalence of MS was 64.3% (95% confidence interval (CI): 61.3%-67.2%) and associated with significantly higher OPG (5.44 vs 4.47 pmol/L) and microvascular complications. The presence of microvascular complications was associated with higher OPG: nephropathy (5.54 (2.20) vs 4.65 (1.70) pmol/L, p < 0.0001), neuropathy (6.33 (2.64) vs 5.06 (1.91) pmol/L, p < 0.0001) and retinopathy (6.08 (2.47) vs 5.00 (1.95) pmol/L, p < 0.0001). After adjusting for age, gender, ethnicity, glucose and microvascular complications, OPG remained an independent predictor of MS: (odds ratio (OR) = 1.102 (95% CI: 1.015-1.196), p = 0.021).. Higher OPG levels were associated with risk of MS and microvascular complications. Studies are needed to test whether OPG could be a useful biomarker identifying patients at risk of vascular complications and whether further exploration of this pathway may lead novel therapeutic options.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Logistic Models; Male; Metabolic Syndrome; Microcirculation; Microvessels; Middle Aged; Odds Ratio; Osteoprotegerin; Predictive Value of Tests; Prevalence; Risk Factors; Singapore; Up-Regulation; Young Adult

Osteoprotegerin (OPG), a soluble member of tumor necrosis factor receptor superfamily that inhibits bone resorption, has been suggested as a cardiovascular risk factor in humans. In this study, we aim to investigate the potential relationship between OPG and MetS (MetS) in a sub-Saharan African population.. Four hundred and eleven volunteers (152 men, 259 women) aged ≥18 years recruited from the general population in Douala and Edea, Cameroon participated in this study. Anthropometric parameters measured and blood samples were collected for glucose, serum lipids and OPG concentrations measurements. Mean differences of the variables in different groups were compared using Students' t test. We performed logistic regressions to analyze the impact of independent factors on the relation between OPG and MetS outcome. MetS was defined using the Joint Interim Statement 2009.. OPG levels did not vary significantly between both men and women with and without MetS (both P>0.05). However, with high fasting blood glucose (≥5.6 mmol/L) had a significantly higher OPG level than those with lower glucose level (P=0.014). In multiple logistic regression analysis, MetS did not show any significant association with serum OPG levels in men and women after adjusting for age, physical activity, alcohol consumption and menopausal status in women (P=0.720 and P=0.930 respectively).. This study failed to demonstrate any relationship between OPG and MetS. Nevertheless, the positive association between blood glucose and OPG levels reveals that OPG might be involved in cardiovascular risk development in this sub-Saharan African population.

Topics: Adult; Africa South of the Sahara; Aged; Aging; Alcohol Drinking; Blood Glucose; Cardiovascular Diseases; Exercise; Fasting; Female; Humans; Logistic Models; Male; Menopause; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Risk Factors; Sex Factors

The relationship between osteoprotegerin (OPG) a glycoprotein related to bone metabolism and the metabolic syndrome (MS) has not been established.. The aim of this study is to evaluate OPG concentration in patients with MS and its association with subclinical atherosclerosis and coronary arterial calcification (CAC).. The study included 238 asymptomatic patients. MS was diagnosed according to the NCEP/ATPIII guidelines. OPG was measured by ELISA. All subjects underwent ultrasonography of the common carotid arteries to measure intima-media thickness (IMT) and evaluate the presence of atheroma plaques. In a subgroup (n=39) CAC was quantified by ECG-triggered cardiac computed tomography. Adipose tissue was excised from 25 patients and OPG expression by RT-PCR and immunohistochemistry was studied.. Patients with the MS (n=60) had higher OPG than patients without (n=178) (p<0.05). OPG correlated with IMT (r=0.2, p=0.005) and patients with atheroma plaques had higher OPG (p=0.008) and also those with coronary artery calcification (p<0.05). OPG expression was confirmed in adipose tissue (n=12) and the expression was significantly higher in patients with MS than in those without (p=0.003).. This study shows that OPG may potentially be a biomarker for cardiovascular risk/damage in the MS and identifies adipose tissue as a potential source of OPG.

Topics: Adipose Tissue; Aged; Atherosclerosis; Biomarkers; Carotid Artery, Common; Carotid Intima-Media Thickness; Coronary Artery Disease; Female; Gene Expression; Humans; Immunohistochemistry; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Reverse Transcriptase Polymerase Chain Reaction; Vascular Calcification

Cardiovascular disease and osteoporosis are important causes of morbi-mortality in the elderly and may be mutually related. Low bone mineral density (BMD) may be associated with increased risk of cardiovascular events. We investigated the prevalence of low bone mass and fractures in metabolic syndrome patients with acute coronary events. A case-control study was conducted with 150 individuals (30-80years-old) with metabolic syndrome. Seventy-one patients had had an acute coronary syndrome episode in the last 6months (cases) and the remaining 79 had no coronary event (controls). Cases and controls were matched for gender, BMI and age. DXA measurements and body composition were performed while spine radiographs surveyed for vertebral fractures and vascular calcification. Biochemical bone and metabolic parameters were measured in all patients. No statistically significant difference in BMD and the prevalence of osteopenia, osteoporosis and non-vertebral fractures was observed between cases and controls. The prevalence of vertebral fractures and all fractures was higher in the cases (14.1 versus 1.3%, p=0.003 and 22.5versus7.6%, p=0.010, respectively). Male gender (OR=0.22 95% CI 0.58 to 0.83, p=0.026) and daily intake of more than 3 portions of dairy products (OR=0.19 95% CI 0.49 to 0.75, p=0.017) were associated with lower prevalence of fractures. Cases had higher risk for fractures (OR=4.97, 95% CI 1.17 to 30.30, p=0.031). Bone mass and body composition parameters were not associated with cardiovascular risk factors or bone mineral metabolism. Patients with fragility fractures had higher OPG serum levels than those without fractures (p<0.001). Our findings demonstrated that patients with recent coronary events have a higher prevalence of vertebral fractures independently of BMD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Body Composition; Bone Density; Brazil; Cardiovascular Diseases; Female; Humans; Lipids; Logistic Models; Lumbar Vertebrae; Male; Metabolic Syndrome; Middle Aged; Osteoporosis; Osteoprotegerin; Prevalence; Spinal Fractures

Osteoprotegerin (OPG), a novel soluble member of tumour necrosis factor receptor superfamily, has been shown to link cardiovascular disorders. The aim of this study is to investigate the potential relationship between serum OPG levels, cardiovascular risk factors and metabolic syndrome in a relatively large group of women with previous GDM. In this cross-sectional case-control study, 128 women with previous GDM and 67 age-matched controls were enrolled. Subjects were evaluated for the diagnosis of metabolic syndrome according to the criteria of the American Heart Association (AHA). Fasting glucose, insulin, serum lipids, CRP and OPG were assayed. HOMA score was calculated. Carotid intima media thickness (IMT) was measured. There was no significant increase in OPG levels in women with previous GDM when compared to controls. On the other hand, women with previous GDM developing metabolic syndrome had higher OPG levels than those without metabolic syndrome and healthy controls. Serum OPG levels were associated with obesity, insulin resistance, serum CRP and carotid IMT. Serum OPG is related to cardiovascular risk factors and metabolic syndrome, and might be involved in the development of cardiovascular disorders in women with previous GDM.

Topics: Adult; Atherosclerosis; C-Reactive Protein; Cardiovascular Diseases; Carotid Arteries; Case-Control Studies; Cross-Sectional Studies; Diabetes, Gestational; Female; Humans; Insulin Resistance; Metabolic Syndrome; Obesity; Osteoprotegerin; Pregnancy; Risk Factors; Tunica Intima; Tunica Media; Turkey; Ultrasonography

Osteoprotegerin (OPG) is an inhibitor of bone resorption. Circulating levels of OPG seem to be elevated in patients with cardiovascular disorders and diabetes. The relationship between OPG and the metabolic syndrome has never been studied in postmenopausal women. In a population-based study, 382 Iranian postmenopausal women were randomly selected. Cardiovascular risk factors, high-sensitivity C-reactive protein, and OPG were measured. The diabetes classification and the metabolic syndrome definition were based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. The mean serum OPG level was higher in those with type 2 diabetes mellitus than those without diabetes (4.33 +/- 1.70 vs 3.84 +/- 1.76 pmol/L, P = .016). In multiple logistic regression analysis, type 2 diabetes mellitus showed a significant association with serum OPG levels when adjustments were made for age, high-sensitivity C-reactive protein, and cardiovascular risk factors (odds ratio = 2.21; confidence interval, 1.34-3.66; P = .002). No significant difference was found between the mean serum OPG levels of those with the metabolic syndrome and those without the metabolic syndrome. Mean OPG levels did not differ significantly between subjects with and without hypertension, dyslipidemia, glucose intolerance, or abdominal obesity according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. In conclusion, circulating OPG levels are significantly associated with diabetes, independent of cardiovascular risk factors in postmenopausal women. However, OPG levels have no correlation with the metabolic syndrome or its components. Further studies are warranted to determine the pathophysiologic origin of elevated OPG in type 2 diabetes mellitus.

Topics: Aged; Aged, 80 and over; Blood Pressure; C-Reactive Protein; Cholesterol; Diabetes Mellitus, Type 2; Female; Humans; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Postmenopause; Statistics, Nonparametric; Triglycerides

Patients with Cushing's syndrome (CS) have a mortality rate four times higher than age- and sex-matched subjects, mainly due to cardiovascular events. Serum osteoprotegerin (OPG) levels are increased in patients with cardiovascular disease and/or excess bone resorption.. The aim of the study was to assess serum OPG and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) levels in CS and their possible relationship with coronary risk profile.. We conducted a cross-sectional study at a tertiary referral center.. We studied 48 adult patients with CS and 48 age- and sex-matched controls. Twenty-six patients had pituitary-dependent CS; five patients had CS caused by ectopic ACTH secretion; and 17 patients had adrenal-dependent CS, accounted for by cortisol-secreting adenoma (n = 9), ACTH-independent macronodular bilateral adrenal hyperplasia (n = 4), or World Health Organization stage II cortisol-secreting carcinoma (n = 4). Patients underwent assessment of the absolute coronary risk and measurement of bone mineral density by dual-energy x-ray absorptiometry. Serum OPG and total sRANKL were measured by ELISA.. Serum OPG (but not sRANKL) levels were significantly higher in CS patients than in controls (P < 0.01). In patients, serum OPG showed a positive correlation with age (r = 0.36; P = 0.01). OPG levels were higher in patients with the metabolic syndrome [median, 1262 (range, 199-2306) pg/ml vs. 867 (412-2479) pg/ml; P = 0.03], and showed a positive correlation with the absolute coronary risk (r = 0.36; P = 0.01). Serum OPG levels were higher in patients with pituitary-dependent CS in comparison with adrenal-dependent CS.. In patients with CS, serum OPG levels are increased and appear to be associated with coronary risk.

Topics: Absorptiometry, Photon; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Cushing Syndrome; Female; Humans; Hydrocortisone; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Pituitary Function Tests; Pituitary Gland; Receptor Activator of Nuclear Factor-kappa B; Risk

The relationship between osteoprotegerin (OPG) and lipid profile, insulin sensitivity, adipocytokines and sex steroids has been poorly studied and subject to controversy. The purpose of this study was to look at the correlates of OPG in an elderly male population.. One hundred and fifty-one nondiabetic, elderly Lebanese men (age range 50-83) were recruited in this cross-sectional study based on voluntary enrolment.. In all the subjects, serum OPG levels were measured and related to clinical parameters (age, waist, body mass index (BMI), systolic and diastolic blood pressure), as well as to metabolic and hormonal parameters. The following fasting laboratory measurements were performed: plasma glucose and insulin levels, total cholesterol, triglycerides and HDL cholesterol, adiponectin, leptin, as well as sex steroids (testosterone, SHBG, free androgen index, ooestradiol, DHEAS), GH and IGF-1. QUICKI index was calculated as a measure of insulin sensitivity.. OPG levels were significantly correlated with age (r = 0.28, P < 0.0001) but not with BMI, waist, systolic or diastolic blood pressure. There was a trend towards higher OPG levels in subjects without, compared to subjects with the metabolic syndrome (3.58 +/- 1.28 vs. 3.26 +/- 1.04 pmol/l, P = 0.09). OPG was negatively correlated with fasting glucose and triglyceride levels (r = -0.18, P = 0.031 and r = -0.19, P = 0.02, respectively) and positively correlated with the QUICKI index (r = 0.17, P = 0.033), HDL cholesterol (r = 0.21, P = 0.009) and adiponectin levels (r = 0.27, P = 0.001). No significant correlations were reported with total or LDL cholesterol levels and with leptin levels. After adjustment for age, OPG is still correlated with triglycerides (r = -0.19, P = 0.02), glucose (r = -0.21, P = 0.011) and adiponectin (r = 0.19, P = 0.02). Finally, OPG was positively associated with SHBG (r = 0.31, P < 0.001) and negatively associated with free androgen index (r =-0.346, P < 0.001); both correlations persisted after adjustment for age (r = 0.21, P = 0.009 and r = -0.23, P = 0.005, respectively). No significant correlation was found between OPG and oestradiol levels while a weak negative correlation was demonstrated with DHEAS (r = -0.18, P = 0.025). Also, no significant correlation was found between OPG and GH or IGF-1 values. In a multiple regression analysis with a stepwise model, the main determinants of OPG were free androgen index and adiponectin (P < 0.0001 and P = 0.015, respectively).. Our results show that circulating OPG levels are favourably associated with some components of the metabolic syndrome. Also, for the first time, an association between OPG and adiponectin is described. Finally, the negative correlation we found between OPG and free androgen index may suggest a potential role of OPG in the increase in cardiovascular disease related to ageing and sex steroid deficiency.

Topics: Adiponectin; Aged; Biomarkers; Coronary Disease; Glycoproteins; Gonadal Steroid Hormones; Humans; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Regression Analysis