osteoprotegerin and Insulin-Resistance

The mortality of end-stage renal disease (ESRD) patients, including those receiving long-term peritoneal dialysis (PD), has remained unacceptably high owing to the prevalence of cardiovascular disease. It is well recognized that both traditional Framingham risk factors and kidney disease-related risk factors may contribute to the high prevalence of cardiovascular disease in these patients. Of the different risk factors, chronic inflammation frequently is observed in long-term PD patients. The causes of inflammation are usually complex and multifactorial, involving both dialysis-related and dialysis-unrelated factors. Inflammation is strongly associated with cardiovascular disease and malnutrition, and has been shown consistently to be a powerful predictor of mortality and adverse cardiovascular outcomes in PD patients. In this article we review the prevalence and potential causes of chronic inflammation in PD patients. More importantly, we provide emerging evidence that shows the serious consequences of chronic systemic inflammation in PD patients and the important contribution of inflammation to adverse clinical outcomes.

Topics: C-Reactive Protein; Cachexia; Calcinosis; Cardiomegaly; Chronic Disease; Heart Failure; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Osteoprotegerin; Peritoneal Dialysis; Prevalence

Osteoprotegerin (OPG) acts as an important regulatory molecule in atherosclerosis. Recent studies report that thiazolidinediones could affect OPG expression. We investigated the relationship between OPG and inflammatory cytokines and the effects of pioglitazone (a PPARγ (PPARG) agonist) versus metformin on serum OPG levels in type 2 diabetic patients.. Sixty-seven type 2 diabetic patients were included in this study. They were assigned to pioglitazone (15 mg/day, n=34) or metformin (1000 mg/day, n=33) during 24 weeks. Various anthropometric and metabolic parameters, OPG, interleukin 6 (IL6), C-reactive protein (CRP), adiponectin, and homeostasis model assessment of insulin resistance (HOMA-IR), were measured at baseline and at 6 months of treatment.. Serum OPG levels correlated significantly with fasting plasma glucose (FPG), HbAlc, HOMA-IR, IL6, and CRP, and inversely correlated with adiponectin after adjusting for age (P<0.05). Multiple regression analysis showed that FPG, HbAlc, and adioponectin were independently correlated with OPG level. After 6 months of treatment, the reduction in FPG and HbAlc levels was similar between the two groups. Pioglitazone treatment significantly increased body mass index (P<0.05) and waist circumference (P<0.05) and decreased triglycerides (P<0.05) and HOMA-IR (P<0.01). The adiponectin concentration was increased (P<0.05), and OPG and CRP levels were decreased in the pioglitazone group (P<0.05), but were unchanged in the metformin group. The changes in serum OPG in the pioglitazone group showed significant correlation with changes in FPG, HbAlc, and adiponectin.. In type 2 diabetic patients, pioglitazone decreases OPG levels, and this decrease in OPG levels might be associated with the increase in adiponectin.

Topics: Adiponectin; Adult; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Metformin; Middle Aged; Osteoprotegerin; Pioglitazone; Thiazolidinediones

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

Topics: Calcium Carbonate; Cardiovascular Diseases; Cholecalciferol; Female; Follow-Up Studies; Genistein; Homocysteine; Humans; Insulin Resistance; Lipids; Middle Aged; Osteoprotegerin; Postmenopause; Research Design; Risk Factors

Obesity and diabetes prevalence are increasing worldwide. We aimed to detect the possible association of osteoprotegerin (OPG) gene expression with visceral adiposity indices and cardiometabolic risk factors among obese women.. The study enrolled 150 controls and 150 obese cases subdivided into two subgroups non-diabetic (n = 70) and 80 patients with type 2 diabetes mellitus (T2DM). Circulating OPG gene expression levels were figured out by real time PCR (Polymerase Chain Reaction). Serum OPG levels were assessed by Enzyme Linked Immunosorbent Assay. Our results explored that OPG serum levels were lower in the obese women compared to control group (p < 0.001) and obese diabetics had higher serum levels of OPG in comparison to obese non-diabetic patients (p < 0.001). Expression levels of OPG were higher in obese women than controls (p < 0.001). Moreover, the blood expression levels of OPG gene were higher in diabetic obese patients than non-diabetics. We found positive correlations between parameters of metabolic syndrome and obesity indices. After adjustment of the traditional risk factors, stepwise linear regression analysis test revealed that OPG expression levels were independently correlated with glycated hemoglobin, high-density lipoprotein-cholesterol, and waist-to-hip ratio.. OPG mRNA levels were associated with surrogate markers of insulin resistance in Egyptian obese women.

Topics: Adult; Biomarkers; Diabetes Mellitus, Type 2; Egypt; Female; Gene Expression Regulation; Humans; Insulin Resistance; Middle Aged; Obesity; Osteoprotegerin

Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects.. The present study investigated the effects of febuxostat on periodontitis in a rat model.. Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined.. In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations.. Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.

Topics: Alveolar Bone Loss; Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Blood Pressure; Body Weight; Disease Models, Animal; Febuxostat; Gingiva; Insulin Resistance; Interleukin-1beta; Ligation; Male; Osteoclasts; Osteoprotegerin; Oxidative Stress; Periodontitis; Rats, Wistar; Tumor Necrosis Factor-alpha; X-Ray Microtomography; Xanthine Dehydrogenase

Obesity and latent inflammation can give rise to insulin resistance and type 2 diabetes. Here we established an insulin resistance model of osteoblasts to explore the restoration effect of anti-inflammatory interleukin-4 (IL-4) on insulin sensitivity and its mechanism. We found that IL-4 inhibited cell proliferation in a concentration- and time-dependent manner. Insulation resistance significantly reduced the phosphorylation levels of the insulin receptor substrate 1 (IRS1; Tyr612), Akt (Ser473), and AS160 (Ser318) proteins. The addition of IL-4 to the insulin resistance model led to a dose-dependent stimulation of the phosphorylation of IRS1, Akt, and AS160. IL-4 fully restored the activation of the insulin cascade in insulin-resistant cells at the concentration of 50 ng/ml. Additionally, IL-4 promoted the expression of IRS1 in a time-dependent manner. We conjecture that IL-4 restores insulin sensitivity in osteoblasts by upregulating the expression of IRS1. It was also found that IL-4 promoted the expression of osteoprotegerin depending on the time of exposure. This effect may play an important role in the regulation of the energy metabolism in the whole body.

Topics: Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cell Survival; Energy Metabolism; Gene Expression Regulation; Humans; Inflammation; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Interleukin-4; Lipids; Obesity; Osteoblasts; Osteoprotegerin; Phosphorylation

To investigate the relationship between osteocalcin and osteoprotegerin as bone markers and inflammatory biomarkers such as adiponectin, leptin, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) in children with nonalcoholic fatty liver disease (NAFLD).. This study included 40 obese children with NAFLD as the patient group and 40 healthy obese children of matched age, sex and BMI as the control group. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood glucose, fasting insulin, Homeostatic model assessment method of insulin resistance (HOMA-IR), lipid profile, osteocalcin, osteoprotegerin, adiponectin, leptin, TNF-α, and IL-6 were measured in all participants.. Children with NAFLD had a significant decrease in osteocalcin, osteoprotegerin and adiponectin level with a significant increase in TNF-α and IL-6 levels. We also found a significant positive correlation between osteocalcin level and adiponectin levels but a significant negative correlation of osteocalcin with each of leptin and TNF-α. However, there was a significant negative correlation between osteoprotegerin levels and both TNF-α and IL-6 levels. Moreover, adiponectin and TNF-α were significant predictors for osteocalcin, and IL-6 was a significant predictor for osteoprotegerin.. Adiponectin, leptin, TNF-α, and IL-6 have potential association with the changes of osteocalcin and osteoprotegerin levels in children with NAFLD.

Topics: Adipokines; Adiponectin; Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Blood Glucose; Body Mass Index; Case-Control Studies; Child; Cytokines; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Male; Non-alcoholic Fatty Liver Disease; Obesity; Osteocalcin; Osteoprotegerin; Tumor Necrosis Factor-alpha

Sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase (B-ALP), which are primarily related to bone metabolism, have been linked with insulin resistance in adults. We aimed to evaluate the association of these markers with growth, obesity, and parameters of insulin resistance in lean and obese children and adolescents.. We measured sclerostin, osteoprotegerin, and B-ALP in fasting and oral glucose tolerance test (oGTT) serum samples from 1,325 children and adolescents, and during 24-h profiles and after exercise and glucose exposure in young adults.. In addition to the positive relationship with height standard deviation scores (SDS), sclerostin (r = 0.035, p < 0.001) and B-ALP (r = 0.06, p = 0.028) increased, whereas osteoprotegerin (r = -0.098, p < 0.001) decreased with BMI SDS. Furthermore, B-ALP correlated with fasting- and oGTT-derived markers of glucose and insulin metabolism suggestive of insulin resistance. To evaluate potential confounding diurnal variation of bone markers, we performed 24-h profiles. B-ALP and osteoprotegerin had lower night-time levels. Exercise acutely and transiently increased B-ALP and osteoprotegerin levels, but glucose ingestion had no effect.. Besides their association with growth, sclerostin and osteoprotegerin levels are altered in childhood obesity. Particularly B-ALP was related to insulin resistance indices. Our findings accent the link between bone, growth, and insulin resistance.

Topics: Adaptor Proteins, Signal Transducing; Adolescent; Adolescent Development; Alkaline Phosphatase; Biomarkers; Bone Morphogenetic Proteins; Child; Child Development; Child, Preschool; Female; Genetic Markers; Humans; Infant; Insulin Resistance; Male; Obesity; Osteoprotegerin

Receptor activator of Nfkb ligand (RANKL) activates, while osteoprotegerin (OPG) inhibits, osteoclastogenesis. In turn a neutralizing Ab against RANKL, denosumab improves bone strength in osteoporosis. OPG also improves muscle strength in mouse models of Duchenne's muscular dystrophy (mdx) and denervation-induce atrophy, but its role and mechanisms of action on muscle weakness in other conditions remains to be investigated. We investigated the effects of RANKL inhibitors on muscle in osteoporotic women and mice that either overexpress RANKL (HuRANKL-Tg+), or lack Pparb and concomitantly develop sarcopenia (Pparb-/-). In women, denosumab over 3 years improved appendicular lean mass and handgrip strength compared to no treatment, whereas bisphosphonate did not. HuRANKL-Tg+ mice displayed lower limb force and maximal speed, while their leg muscle mass was diminished, with a lower number of type I and II fibers. Both OPG and denosumab increased limb force proportionally to the increase in muscle mass. They markedly improved muscle insulin sensitivity and glucose uptake, and decrease anti-myogenic and inflammatory gene expression in muscle, such as myostatin and protein tyrosine phosphatase receptor-γ. Similarly, in Pparb-/-, OPG increased muscle volume and force, while also normalizing their insulin signaling and higher expression of inflammatory genes in skeletal muscle. In conclusions, RANKL deteriorates, while its inhibitor improves, muscle strength and insulin sensitivity in osteoporotic mice and humans. Hence denosumab could represent a novel therapeutic approach for sarcopenia.

Topics: Animals; Bone and Bones; Cell Line; Denosumab; Female; Humans; Insulin Resistance; Male; Mice; Mice, Transgenic; Muscle Strength; Organ Size; Osteoporosis; Osteoprotegerin; PPAR-beta; RANK Ligand; Sarcopenia

Obesity is a complex disorder that is influenced by genetic and environmental factors. DNA methylation is an epigenetic mechanism that is involved in development of obesity and its metabolic complications. The aim of this study was to investigate the association between the RANKL and c-Fos gene methylation on obesity with body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), plasma leptin, adiponectin and resistin levels. The study included 68 obese and 46 non-obese subjects. Anthropometric parameters, including body weight, body mass index, waist circumference, and waist-hip ratio, were assessed. Serum glucose, triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), plasma leptin, adiponectin and resistin levels were measured. Methylation status of RANKL and c-Fos gen were evaluated by MS-HRM. Statistically significant differences were observed between obese patients and the controls with respect to RANKL and c-Fos gene methylation status (p < 0.001). Also, statistically significant importance was observed RANKL gene methylation and increased level of leptin in obese subjects (p = 0.0081). At the same time, statistically significant association between methylation of c-Fos and increased level of adiponectin was observed in obese patients (p = 0.03) On the other hand, decreased level of resistin was observed where the c-Fos was unmetyladed in controls (p = 0.01). We conclude that methylation of RANKL and c-Fos genes have significant influences on obesity and adipokine levels. Based on literature this was the first study which shows the interactions between RANKL and c-Fos methylation and obesity.

Topics: Adiponectin; Adult; Anthropometry; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation; Genes, fos; Humans; Insulin Resistance; Leptin; Male; Obesity; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction; Triglycerides

Type 2 diabetes is an emerging global health epidemic. Foundations for new therapies are arising from understanding interactions between body systems. Bone-derived factors that reduce RANKL (receptor activator of NF-kappa B ligand) signaling in the liver may prevent insulin resistance and the onset of type 2 diabetes. Here we demonstrate that deletion of the epigenetic regulator, Hdac3, in Osx1-expressing osteoprogenitors prevents insulin resistance induced by high fat diet by increasing serum and skeletal gene expression levels of osteoprotegerin (Opg), a natural inhibitor of RANKL signaling. Removal of one Opg allele in mice lacking Hdac3 in Osx1+ osteoprogenitors increases the insulin resistance of the Hdac3-deficient mice on a high fat diet. Thus, Hdac3-depletion in osteoblasts increases expression of Opg, subsequently preserving insulin sensitivity. The Hdac inhibitor vorinostat also increased Opg transcription and histone acetylation of the Opg locus. These results define a new mechanism by which bone regulates systemic insulin sensitivity.

Topics: Alleles; Animals; Biomarkers; Bone and Bones; Diet, High-Fat; Gene Deletion; Histone Deacetylases; Insulin Resistance; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts; Osteoprotegerin; RNA, Messenger; Stem Cells; Weight Gain

Surgical treatment for primary hyperparathyroidism (PHPT) improves bone metabolism. Osteocalcin (OC) and its undercarboxylated form (ucOC) are associated with bone and energy metabolism. Osteopontin (OPN), a multifunctional protein expressed in bone, is involved in resorption, along with β-carboxyl-terminal cross-linking telopeptide of type 1 collagen (β-CTX), and osteoprotegerin (OPG). Our aim was to investigate these biomarkers of bone metabolism in patients with PHPT.. We examined 30 individuals with PHPT, in a clinical research facility, before and 1 month following parathyroidectomy. Circulating levels of OC, ucOC, OPN, β-CTX, and OPG were examined as bone biomarkers along with inflammatory markers (e.g., interleukin-6 [IL-6], lipocalin-2), insulin resistance (i.e., homeostasis model assessment for insulin resistance [HOMA-IR]), adiposity (i.e., leptin, adiponectin), PTH, calcium, 25-hydroxyvitamin D, creatinine, and demographics.. The lower 1-month postoperative OPN and ucOC levels in PHPT seem to indicate reduced bone resorption. Decreased ucOC levels may also suggest lower energy demands postoperatively.

Topics: Adiponectin; Aged; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Primary; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Parathyroidectomy

To examine the relationship between hormones involved in bone remodeling and glucose metabolism alterations in prediabetes.. OPN was higher in IGR compared to NGT (5.3 ± 0.5 vs. 3.3 ± 0.2 μg/mL; p = 0.008) and in isolated IGT compared to IFG and IFG-IGT (6.3 ± 0.5 vs. 4.5 ± 0.3 and 5.4 ± 0.5 μg/mL; p = 0.02). OCN was similar in IFG and NGT but lower in IGT and IFG-IGT compared to NGT (7.2 ± 0.3 and 5.4 ± 0.2 vs. 8.3 ± 0.3 ng/mL; p < 0.01). OPN was positively correlated with HbA1c, fasting and 2 h plasma glucose and PTH. OCN was negatively correlated with body fat, 2 h plasma glucose, insulin and positively correlated with Stumvoll index. OPG correlated with TGD/SSPI (r = - 0.29; p < 0.05), EGP, and hepatic insulin resistance index in IGR (r = 0.51, r = 0.43; p < 0.01). There was no correlation between PTH and insulin sensitivity or Beta-cell function parameters.. In prediabetes, hormones known to be involved in bone remodeling may affect glucose metabolism before overt T2DM occurs with tissue-specific mechanisms.

Topics: Adult; Blood Glucose; C-Peptide; Case-Control Studies; Fasting; Female; Glucose Clamp Technique; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Prediabetic State

Tissue cross-talk is emerging as a determinant way to coordinate the different organs implicated in glucose homeostasis. Among the inter-organ communication factors, muscle-secreted myokines can modulate the function and survival of pancreatic beta-cells. Using primary human myotubes from soleus, vastus lateralis and triceps brachii muscles, we report here that the impact of myokines on beta-cells depends on fiber types and their metabolic status. We show that Type I and type II primary myotubes present specific mRNA and myokine signatures as well as a different sensitivity to TNF-alpha induced insulin resistance. Finally, we show that angiogenin and osteoprotegerin are triceps specific myokines with beta-cell protective actions against proinflammatory cytokines. These results suggest that type I and type II muscles could impact insulin secretion and beta-cell mass differentially in type 2 diabetes through specific myokines secretion.

Topics: Cytokines; Diabetes Mellitus, Type 2; Homeostasis; Humans; Inflammation; Insulin Resistance; Insulin-Secreting Cells; Muscle Cells; Muscle Fibers, Skeletal; Muscle, Skeletal; Osteoprotegerin; Primary Cell Culture; Ribonuclease, Pancreatic; Tumor Necrosis Factor-alpha

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

Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters.. Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined.. Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels.. Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.

Topics: Adipose Tissue; Adult; Aged; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Male; Middle Aged; Osteoprotegerin; Prediabetic State; RANK Ligand

Osteoprotegerin (OPG) is closely related to insulin resistance and bone remodeling. However, no studies have examined the role of OPG in postmenopausal women with coexistent impaired glucose and bone regulation. The present study investigated the relationship of OPG to glucose homeostasis and insulin resistance in postmenopausal osteoporotic women with different types of glucose tolerance.. In all, 114 postmenopausal osteoporotic women were divided into three groups according to glucose tolerance status: 51 with normal glucose tolerance (NGT, group 1), 31 with impaired glucose tolerance (IGT, group 2), and 32 with type 2 diabetes mellitus (DM, group 3). Study participants were evaluated for metabolic parameters, OPG, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and bone mineral density parameters.. The OPG levels differed significantly across groups and increased from group 1 to group 3 in a continuous fashion (analysis of variance, P < 0.0001). In post-hoc analysis, OPG was significantly lower in osteoporotic women with NGT, than participants with IGT and DM (P < 0.05 and P < 0.0001, respectively). OPG was positively associated with HOMA-IR (P < 0.0001). No association between serum OPG levels and measures of BMD was observed. In a multiple regression analysis, OPG emerged as an independent predictor of HOMA-IR even after controlling for age, body mass index, and creatinine.. OPG is significantly higher in postmenopausal osteoporotic women with impaired glucose regulation (IGT and DM) than women with NGT. OPG was independently associated with insulin resistance assessed by HOMA-IR. Thus, measurement of OPG may potentially be considered as a prediabetic state screening in postmenopausal osteoporotic women.

Topics: Aged; Bone Density; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Osteoporosis, Postmenopausal; Osteoprotegerin

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

Identification of risk factors may help us to understand the pathogenesis of osteoporotic hip fracture as well as to formulate development of better diagnostic, prevention and treatment strategies. The present study was designed to determine the impact of multiple metabolic risk factors such as markers of systemic inflammation (C-reactive protein), immune responses-acute phase reactants (ferritin), insulin resistance (HOMA-IR) and bone remodeling (osteoprotegerin), for the prediction of hip fractures in postmenopausal osteoporotic women. The study group consisted of 115 postmenopausal women divided into two groups: Group 1 consisted of 49 women hospitalized in the Orthopedic Department, Wolfson Medical Center for the diagnosis of non-traumatic hip fracture and Group 2 contained 66 postmenopausal osteoporotic women without a history of hip fracture. Metabolic parameters were determined. Circulating OPG was significantly higher in Group 1 than in Group 2 (205.2 ± 177.1 vs 60.0 =/-22.3, p < 0.0001). While levels of hemoglobin (Hbg) as well as MCV and MCH did not differ between groups, circulating ferritin was significantly increased in Group 1 compared to the control Group 2 (217.9 ± 195.1 vs 49.7 ± 31.3, p < 0.0001). In multiple linear regression analysis, which explains about 40 % of the variability in CRP, 42 % in OPG, and 28 % in ferritin, significant by-group differences in terms of these parameters persisted even after adjustment. Elevated serum ferritin concentrations and bone remodeling marker, osteoprotegerin, are independent predictors of hip fracture in postmenopausal women hospitalized for fragility fracture.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Female; Ferritins; Hip Fractures; Humans; Insulin Resistance; Mass Screening; Middle Aged; Osteoprotegerin; Postmenopause; Vitamin D

Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study. Metabolic and anthropometric parameters, insulin resistance variables, osteoprotegerin, and nuclear factor-B ligand markers, carotid intima media thickness were examined at baseline for all participants. To evaluate the effect of therapy we determined the same parameters after the end of the study. Measurements of waist circumference, body mass index, body fat percentage and levels of fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance, triglyceride levels and hsCRP and carotid intima media thickness were significantly higher in patients with prediabetes (p < 0.05). We also found higher osteoprotegerin and lower nuclear factor-B ligand levels in patients than in controls however, the value was non-significant (p > 0.05). Patients with prediabetes were under lifestyle interventions with (group 1, n = 33) or without metformin (group 2, n = 21) therapy. Baseline anthropometric and metabolic characteristics were not found statistically different in group 1 and group 2. Mean follow up period of the patients were 7.9 ± 2.2 month (min-max: 6-12 months). After the follow up period we evaluated the same parameters and found significant differences between waist circumference, body mass index, body fat percentage, fasting insulin, homeostatic model assessment of insulin resistance, and osteoprotegerin levels (p < 0.05). However, carotid intima media thickness, and nuclear factor-B ligand levels significantly different only in the group treated with metformin (p < 0.05). We also compared the variables after the treatment period with the control group and found significantly lower levels in terms of fasting insulin, homeostatic model assessment of insulin resistance, waist circumference, body mass index, body fat percentage, carotid intima media thickness, osteoprotegerin, and nuclear factor-B ligand values (p < 0.05). C

Topics: Adult; Blood Glucose; Body Mass Index; Fasting; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Life Style; Male; Metformin; Middle Aged; Osteoprotegerin; Prediabetic State; RANK Ligand; Treatment Outcome; Waist Circumference

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

Coronary artery calcification (CAC) is a prominent feature of atherosclerosis and is associated with cardiovascular events. In vitro studies have suggested that osteoprotegerin (OPG) and osteocalcin (OC) exert anticalcification potential in the vessel wall. The objective of this study was to investigate the association of CAC and serum bone biomarkers in persons with type 2 diabetes.. We examined 50 individuals with type 2 diabetes. CAC imaging was performed by multidetector computed tomography. CAC scores ≥10, expressed in Agatston units, were considered abnormal. OC, undercarboxylated OC (ucOC), and OPG levels were determined by enzyme-linked immunosorbent assay.. Abnormal CAC scores were found for 64% of the study cohort. OPG levels were significantly elevated (5.5 ± 2.0 pmol/L vs. 4.2 ± 1.7 pmol/L; P = .026) for those with abnormal CAC scores. No univariate differences were found for OC or ucOC. Logistic regression analyses revealed that an increase in serum OPG level was significantly associated with an increase in CAC score (odds ratio, 3.324; 95% confidence interval, 1.321 to 8.359; P = .011). Longer duration of diabetes was a significant covariate (P = .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. The Nagelkerke R2 for the model was 0.66. Neither OC nor ucOC were significantly associated with elevated CAC scores.. Our results suggest that OPG is a more useful serum biomarker than OC or ucOC for identifying those at increased risk of arterial calcification in type 2 diabetes.

Topics: Aged; Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Logistic Models; Male; Middle Aged; Osteocalcin; Osteoprotegerin; Vascular Calcification

The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD).. The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red.. Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)].. In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

Topics: Adult; Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Cohort Studies; Coronary Artery Disease; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Incidence; Inflammation; Insulin Resistance; Interleukin-6; Kidney Failure, Chronic; Logistic Models; Middle Aged; Multivariate Analysis; Osteocalcin; Osteopontin; Osteoprotegerin; Oxidative Stress; Radial Artery; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Serum Amyloid P-Component; Severity of Illness Index; Tunica Media; Vascular Calcification

Growing evidence suggests the presence of a complex interplay between hypertension as well as type 2 diabetes mellitus (DM) and osteoporosis. The present study was designed to investigate a possible effect of type 2 DM on bone remodelling markers such as osteoprotegerin and N-terminal propeptide of type 1 collagen (P1NP) in hypertensive patients.. The 100 study participants were divided into three groups according to the presence of DM and hypertension: group one included diabetic hypertensive subjects, group 2 included hypertensive subjects without diabetes and group 3 included subjects without hypertension and without DM (controls). Blood sampling for metabolic parameters, including osteoprotegerin, P1NP, adiponectin, fasting glucose, HbA1c , CRP, homeostasis model assessment-insulin resistance, homeostasis model assessment-beta function was performed.. Circulating P1NP increased from group 1 to group 3 in a continuous fashion. P1NP was significantly lower in hypertensive subjects with DM (group 1), than in groups 2 and 3 (p < 0.0001). P1NP, was marginally lower in diabetic hypertensive subjects as compared with nondiabetic subjects with hypertension (p = 0.079). Circulating osteoprotegerin did not differ significantly between groups (p = 0.593).. In the present study, bone formation marker, P1NP, was significantly lower in diabetic hypertensive subjects as compared with nondiabetic subjects with and without hypertension. P1NP was inversely associated with parameters of glucose homeostasis such as fasting glucose, HbA1c and positively with homeostasis model assessment-beta cell function. Type 2 DM was associated with an adverse effect on bone formation independently of age, sex and exposure to anti-diabetic drugs.

Topics: Adiponectin; Aged; Biomarkers; Blood Glucose; Bone and Bones; Bone Remodeling; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypertension; Insulin Resistance; Male; Middle Aged; Osteoporosis; Osteoprotegerin; Peptide Fragments; Procollagen

We measured the levels of osteoprotegerin, resistin, leptin, and adiponectin in patients with hypothyroidism differing in the thyroid status. The levels of osteoprotegerin, resistin, leptin were higher and those of adiponectin lower than normal. The patients suffered atherogenic dyslipidemia associated with enhanced insulin resistance and compensatory hyperinsulinemia. Leptin and adiponectin levels correlated with characteristics of lipid metabolism. It is concluded that leptin and adiponectin play a role in the development of dyslipidemia in hypothyroidism.

Topics: Adipokines; Anthropometry; Atherosclerosis; Dyslipidemias; Female; Humans; Hypothyroidism; Insulin Resistance; Lipid Metabolism; Middle Aged; Osteoprotegerin; Risk Factors

High osteoprotegerin (OPG) has been reported in association with insulin resistance and type 2 diabetes. We aimed to evaluate the association of serum OPG with impaired glucose regulation (IGR) and microalbuminuria among middle-aged and older Chinese.. Serum OPG was measured in 599 individuals with normal glucose regulation, 730 with impaired glucose regulation and 327 newly diagnosed patients with diabetes. Serum OPG was measured using ELISA methods and urine albumin/creatinine ratio was used to determine the urinary albumin excretion.. Serum OPG levels were significantly higher in subjects with isolated impaired fasting glucose, isolated impaired glucose tolerance, combined impaired fasting glucose/impaired glucose tolerance and diabetes than in those with normal glucose regulation, whereas serum OPG levels were not different in the four groups with dysregulation of glucose metabolism. OPG was associated with a higher risk for IGR (OR 1.108 for each 0.1 μg/l increase in OPG, 95% CI 1.009-1.117, p = 0.01) after adjustment for gender, age, BMI, current smoking and alcohol intake, family history of diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile; the corresponding OR of combined impaired glucose regulation and type 2 diabetes was 1.121 (95% CI 1.101-1.141, p = 0.0005). OPG was associated with the risk of microalbuminuria (OR 1.025, 95% CI 1.006-1.044, p = 0.02) after adjustment for gender, age, current smoking, current alcohol intake, family history of diabetes, BMI, waist/hip ratio, HOMA-IR, eGFR and lipid profile.. Serum OPG level is closely and independently associated with IGR and is an independent risk factor for microalbuminuria.

Topics: Aged; Albuminuria; Biomarkers; C-Reactive Protein; China; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Longitudinal Studies; Male; Middle Aged; Osteoprotegerin; Prediabetic State

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

Some data indicate a potential relationship between insulin resistance level and the concentration of osteoprotegerin (OPG) in the body. There have been few studies concerning OPG level and its relationship with insulin resistance and body composition in young people. The aim of this study was to assess serum osteoprotegerin concentration in obese adolescents, and to evaluate its potential association with insulin resistance. Seventy-eight obese adolescents and 20 healthy volunteers aged 12-18 years were recruited in the study. Selected anthropometrical measurements and blood biochemical analyses were performed. Insulin resistance in the participants was evaluated according to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol. Level of OPG was assessed in serum. Obese subjects had significantly higher HOMA-IR indices and OPG levels in serum than the control group. A significant positive correlation between OPG and insulin resistance was found. It was observed that high concentrations of osteoprotegerin are associated with insulin resistance in obese adolescents.

Topics: Adolescent; Blood Glucose; Body Composition; Body Mass Index; Case-Control Studies; Child; Female; Gene Expression; Humans; Insulin; Insulin Resistance; Male; Obesity; Osteoprotegerin

Today the prevalence of type 2 diabetes reached an epidemic level. It is known that type 2 diabetes could only be prevented before the manifestation, during the "prediabetic" state, urging the development of diagnostic tests to recognize the group at risk in time.. The authors explored metabolic differences between healthy, normal glucose tolerant, normal insulin resistant females having first degree relatives with and without type 2 diabetes.. Healthy, normal insulin sensitive females without (n = 26) and with (n = 18) type 2 diabetic relatives were investigated.. Healthy females with first degree diabetic relatives had lower low density lipoproteins and higher high density lipoproteins as well as higher glucose and insulin levels at the 120 min of oral glucose test as compared to those without first degree diabetic relatives.. These results suggest that the appearance of insulin resistance is preceded by hepatic insulin resistance and impaired lipid metabolism in the symptom-free prediabetic period of genetically susceptible females.. Bevezetés: A 2-es típusú cukorbetegség ma már „világjárvány”, megelőzése csak a „praediabetes” idején eredményes, ezért olyan szűrővizsgálatokra van szükség, amelyek a cukorbetegség várományosait időben felfedik. Célkitűzés: A szerzők célul tűzték ki egészséges, negatív családi anamnézisű (genetikailag nem diabeteses) és elsőfokú cukorbeteg rokonokkal rendelkező (genetikailag diabeteses), normális szénhidrát-toleranciájú és inzulinérzékenységű nőkben a diagnosztikai értékű anyagcsere-eltérések feltárását. Módszer: A klemp vizsgálatok során normális inzulinérzékenységű, genetikailag nem diabeteses (n = 26) és genetikailag diabeteses (n = 18) önkéntesek adatait elemezték. Eredmények: Genetikailag diabeteses, egészséges nőkben az orális cukorterhelés 120. percében magasabb glükóz- és inzulinkoncentrációt, valamint nagyobb magas denzitású és kisebb alacsony denzitású lipidszintet találtak a genetikailag nem diabeteses egészséges nőkben mért értékekhez képest. Következtetések: Az eredmények szerint genetikailag diabeteses, egészséges nőkben a kialakuló inzulinrezisztenciát megelőzi a hepaticus inzulinrezisztencia és a zsíranyagcsere zavara. A szerzők nem kaptak választ arra a kérdésre, hogy a cukorbetegséghez és az elhízáshoz vezető energiafelesleg miért okoz genetikailag diabeteses nőkben korán zsíranyagcsere-zavart és hyperinsulinaemiát, továbbá arra sem, hogy az elhízás miért nem társul mindig inzulinrezisztenciával. Orv. Hetil., 2013, 154, 1747–1753.

Topics: Adipokines; Adult; Aged; Biomarkers; Blood Glucose; C-Reactive Protein; Diabetes Mellitus, Type 2; Family; Female; Follicle Stimulating Hormone; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Interleukin-6; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Obesity; Osteocalcin; Osteoprotegerin; Prediabetic State; Triglycerides; Tumor Necrosis Factor-alpha

Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance.. 115 men underwent a 75 g oral glucose tolerance test. OPG, hsCRP and adiponectin were measured using ELISA. IR was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR).. Men with abnormal glucose tolerance (n=38) were older (58.3±11.2 vs 47.3±11.4 years, P<.001), had higher body mass index (BMI) (31.1±2.9 vs 27.9±3.2 kg/m(2), P<.001) and were more insulin resistant (median (I.Q.) HOMA-IR 5.88 (3.38) vs 1.13 (1.14), P<.001) than those with normal glucose tolerance (n=77). After adjustment for age and BMI, OPG (6.28 (2.32) vs 5.16 (1.86) pmol/L, P<.001) and hsCRP (2.07 (5.47) vs 0.78 (1.05) mg/L, P<.001) were higher and adiponectin (3.02±1.17 vs 4.78±2.38 μg/mL, P<.001) was lower in those with AGT. After adjustment for age and BMI, adiponectin (r=-0.317, P<.001) and hsCRP (r=0.318, P<.001), but not OPG (r=0.126, P=.196) correlated with HOMA-IR. On multiple linear regression analysis, adiponectin and hsCRP but not OPG were independent predictors of HOMA-IR.. OPG is higher in individuals with abnormal glucose tolerance, but unlike adiponectin and hsCRP, does not correlate with HOMA-IR, suggesting its elevation within this cohort of individuals is due to factors other than insulin resistance.

Topics: Adiponectin; Area Under Curve; Biomarkers; C-Reactive Protein; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Glucose Tolerance Test; Humans; Insulin Resistance; Linear Models; Male; Middle Aged; Osteoprotegerin

Results of animal studies suggest that osteocalcin (OC) plays an important role in the regulation of carbohydrate metabolism. The aim of the present study was to assess the relationship between biochemical indices of bone turnover and carbohydrate metabolism in postmenopausal women subjected to aerobic training for 8 weeks. The study was conducted on 44 postmenopausal women: 27 of them participated in the training program, and 17 did not undertake any additional physical activity during the study period (control group). Subjects performed a cycle-ergometer physical workout at a level of 70% to 80% of ventilatory threshold intensity for 8 weeks (40-minute sessions, 3 times per week). Serum concentrations of OC, C-terminal telopeptide of type I collagen, osteoprotegerin (OPG), insulin, and glucose were measured; and the homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated before and after the 8-week training program. The training program caused significant decrease in levels of OC (P < .05), HOMA-IR (P < .05), and waist-to-hip ratio (P < .05). No significant changes were observed in C-terminal telopeptide of type I collagen, OPG, insulin, and glucose concentrations. Pretraining OC levels inversely correlated with concentrations of OPG (P < .05), glucose (P < .05), and insulin (P < .05) and with HOMA-IR values (P < .05). Our study revealed an association between serum OC concentrations and metabolic markers in postmenopausal women. Regular physical activity was associated with decrease in central adiposity and OC levels and slight reduction of insulin resistance. However, no direct relationships between training-related changes in OC concentrations and metabolic markers were observed.

Topics: Aged; Collagen Type I; Exercise; Female; Glucose; Humans; Insulin Resistance; Middle Aged; Osteocalcin; Osteoprotegerin; Peptides; Postmenopause; Statistics, Nonparametric

Osteogenic differentiation of vascular smooth muscle cells (VSMCs) results in medial artery calcification, which is common in diabetes, but the pathogenesis is poorly understood. We aimed to explore the pathophysiological roles of insulin resistance (IR) on medial artery calcification in rats with 10% fructose in drinking water. After 12 weeks of fructose feeding, rats showed severe IR, with increased levels of fasting blood glucose, serum insulin and oral glucose tolerance test (OGTT). Fructose-fed rats showed aortic calcification, increased aortic calcium deposition and irregular elastic fibers in the medial layer of the vessel wall. Moreover, plasma phosphorus concentration, calcium × phosphorus product and alkaline phosphatase (ALP) activity, and aortic calcium content and ALP activity were significantly increased. Fructose feeding increased mRNA levels of osteopontin, type III sodium-dependent phosphate co-transporter, bone morphogenetic protein-2 and the key transcription factor core binding factor alpha 1 in aortic tissue and downregulated mRNA levels of osteoprotegerin and matrix γ-carboxyglutamic acid protein. Fructose feeding decreased protein levels of smooth-muscle lineage markers and induced severe lipid peroxidation injury. IR induced by high fructose feeding could evoke osteogenic transdifferentiation of VSMCs and promote vascular calcification.

Topics: Alkaline Phosphatase; Animals; Aorta, Thoracic; Blood Glucose; Bone Morphogenetic Proteins; Calcium; Calcium-Binding Proteins; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dietary Carbohydrates; Extracellular Matrix Proteins; Fructose; Glucose Tolerance Test; Insulin; Insulin Resistance; Lipid Peroxidation; Male; Matrix Gla Protein; Muscle, Smooth, Vascular; Osteopontin; Osteoprotegerin; Phosphorus; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sodium-Phosphate Cotransporter Proteins, Type III; Tunica Media; Vascular Calcification

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

There is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim is to investigate the relationships of OPG/free soluble receptor activator of nuclear factor κB ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilation (FMD), and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control, and endothelial injury.. A cross-sectional, observational study.. Hormonal and metabolic profiles, FMD, CIMT, serum OPG, and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry.. OPG was significantly lower in PCOS and related negatively to free testosterone and positively to estradiol (E(2)) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices, and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared with all other quartile groups together (P=0.012). In PCOS, multiple regression analysis retained E(2)/sex hormone-binding globulin ratio, fat mass, and homeostasis model assessment of insulin resistance as independent predictors of OPG.. In PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independent of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.

Topics: Adult; Biomarkers; Blood Flow Velocity; Body Composition; Brachial Artery; Carotid Arteries; Cross-Sectional Studies; Endothelium, Vascular; Estradiol; Female; Humans; Insulin; Insulin Resistance; Osteoprotegerin; Polycystic Ovary Syndrome; Prospective Studies; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone; Tunica Intima; Tunica Media; Vasodilation

An increase in serum osteoprotegerin (OPG) is associated with type 2 diabetes mellitus, the severity of vascular calcification, and coronary artery disease. Obesity is a risk factor for diabetes and cardiovascular disease, but little is known about the relationship between OPG and obesity. The purpose of this study was to determine if changes in body mass index (BMI) and insulin sensitivity influence circulating OPG in healthy subjects. A total of 100 subjects (36 lean, 41 overweight, and 23 obese) with normal glucose tolerance, blood pressure, and electrocardiogram stress test result volunteered for this study. Insulin sensitivity was estimated using a 2-hour oral glucose tolerance test with oral glucose insulin sensitivity analysis. Osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),soluble receptor activator of nuclear factor-κβ ligand (sRANKL), and adiponectin were analyzed using commercially available enzyme-linked immunosorbent assays. Osteoprotegerin (P < .01) and adiponectin (P < .001) were significantly decreased in the obese compared with lean subjects. There was no significant difference between BMI categories for TRAIL or sRANKL. Controlling for age and sex, there was a significant correlation between OPG and adiponectin (r = 0.391, P < .001), BMI (r = -0.331, P < .001), waist circumference (r = -0.268, P < .01), homeostasis model assessment of insulin resistance (r = -0.222, P < .05), and oral glucose insulin sensitivity (r = 0.221, P < .05). Both OPG and adiponectin were negatively correlated with body weight, BMI, waist circumference, and fasting plasma insulin while being positively correlated with insulin sensitivity (P < .05). Controlling for age, sex, and BMI, TRAIL was positively related to fat mass (r = 0.373, P < .001) and waist circumference (r = 0.257, P < .05). In contrast to patients with type 2 diabetes mellitus, circulating OPG is lower in obese, but otherwise healthy subjects and is positively correlated with indices of insulin sensitivity.

Topics: Adiponectin; Adult; Blood Pressure; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Osteoprotegerin; RANK Ligand; TNF-Related Apoptosis-Inducing Ligand; Waist Circumference

Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. Negative associations exist between circulating OPG and cardiac function. The adipocytokine adiponectin (ADPN) is downregulated in type 2 diabetes mellitus (T2DM) and coronary artery disease and shows an inverse correlation with insulin sensitivity and cardiovascular disease risk. We assessed the relationship of plasma OPG and ADPN and arterial function, cardiac function and myocardial glucose metabolism in T2DM.. We included 78 asymptomatic men with uncomplicated, well-controlled T2DM, without inducible ischemia, assessed by dobutamine-stress echocardiography, and 14 age-matched controls. Cardiac function was measured by magnetic resonance imaging, myocardial glucose metabolism (MMRglu) by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography. OPG and ADPN levels were measured in plasma.. T2DM patients vs. controls showed lower aortic distensibility, left ventricular (LV) volumes, impaired LV diastolic function and MMRglu (all P < 0.05). In T2DM men vs. controls, OPG levels were higher (P = 0.02), whereas ADPN concentrations were decreased (P = 0.04). OPG correlated inversely with aortic distensibility, LV volumes and E/A ratio (diastolic function), and positively with LV mass/volume ratio (all P < 0.05). Regression analyses showed the associations with aortic distensibility and LV mass/volume ratio to be independent of age-, blood pressure- and glycated hemoglobin (HbA1c). However, the associations with LV volumes and E/A ratio were dependent of these parameters. ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.. OPG was inversely associated with aortic distensibility, LV volumes and LV diastolic function, while ADPN was positively associated with MMRglu. These findings indicate that in asymptomatic men with uncomplicated T2DM, OPG and ADPN may be markers of underlying mechanisms linking the diabetic state to cardiac abnormalities.. Current Controlled Trials ISRCTN53177482.

Topics: Adiponectin; Aorta; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Heart; Humans; Hypertrophy, Left Ventricular; Insulin Resistance; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Osteoprotegerin; Positron-Emission Tomography; Ventricular Dysfunction, Left

It has been suggested that hormones released after nutrient absorption, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 2 (GLP-2), could be responsible for changes in bone resorption. However, information about the role of GLP-1 in this regard is scanty. Diabetes-related bone loss occurs as a consequence of poor control of glucose homeostasis, but the relationship between osteoporosis and type 2 diabetes remains unclear. Since GLP-1 is decreased in the latter condition, we evaluated some bone characteristics in streptozotocin-induced type 2 diabetic (T2D) and fructose-induced insulin-resistant (IR) rat models compared to normal (N) and the effect of GLP-1 or saline (control) treatment (3 days by osmotic pump). Blood was taken before and after treatment for plasma measurements; tibiae and femora were collected for gene expression of bone markers (RT-PCR) and structure (microCT) analysis. Compared to N, plasma glucose and insulin were, respectively, higher and lower in T2D; osteocalcin (OC) and tartrate-resistant alkaline phosphatase 5b were lower; phosphate in IR showed a tendency to be higher; PTH was not different in T2D and IR; all parameters were unchanged after GLP-1 infusion. Bone OC, osteoprotegerin (OPG) and RANKL mRNA were lower in T2D and IR; GLP-1 increased OC and OPG in all groups and RANKL in T2D. Compared to N, trabecular bone parameters showed an increased degree of anisotropy in T2D and IR, which was reduced after GLP-1. These findings show an insulin-independent anabolic effect of GLP-1 and suggest that GLP-1 could be a useful therapeutic agent for improving the deficient bone formation and bone structure associated with glucose intolerance.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Resorption; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucagon-Like Peptide 1; Glucose; Insulin; Insulin Resistance; Isoenzymes; Male; Osteocalcin; Osteoprotegerin; Parathyroid Hormone; Peptide Fragments; RANK Ligand; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

Presented here is a first-person account of the evolution of the practice of surgical neurootology to that of medical neurootology shaped mainly by results of treatment directed at underlying otosclerosis-like lesions of the otic capsule and metabolic factors. With new technologies and rapidly evolving concepts, the changing treatment algorithms did not remain constant to provide the usual evidence-based outcome analyses. However, the majority of the patients presenting with neurootological symptoms had undergone previous medical or surgical treatment before undergoing the medical management herein described. The underlying ongoing basic science findings over this period were linked to the clinical observations. On the basis of the more effective results of treating neurootological disorders, recommendations are made for future areas of investigation-mostly basic science-into developing an investigative foundation for future effective management of patients with a variety of neurootological disorders.

Topics: Animals; Blood Glucose; Bone Density Conservation Agents; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Diabetes Mellitus, Type 2; Diphosphonates; Evidence-Based Medicine; Hair Cells, Auditory; Hearing Loss, Sensorineural; Humans; Insulin Resistance; Labyrinth Diseases; Meniere Disease; Mice; Mice, Knockout; Migraine Disorders; Osteoclasts; Osteoprotegerin; Otosclerosis; Tinnitus; Tumor Necrosis Factor-alpha

Our objective of this study is to investigate the relationship between plasma osteoprotegerin (OPG) levels in type 2 diabetes and its relationship with the insulin resistance, HbA(1c), CRP, and TNF-alpha levels.. In a cross-sectional study, levels of OPG were determined in 50 subjects with type 2 diabetes and 59 control subjects without diabetes. The OPG levels between the groups were compared and their correlation with insulin resistance, glycemia and inflammatory markers CRP and TNF-alpha was determined.. OPG levels were elevated in subjects with diabetes (6.8+/-0.27 pmol/l), compared to control subjects (5.7+/-0.26 pmol/l). OPG levels significantly correlate with insulin, insulin resistance, CRP, and TNF-alpha.. OPG levels are significantly correlated with insulin resistance and may reflect the proinflammatory state in type 2 diabetes.

Topics: C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Osteoprotegerin; Tumor Necrosis Factor-alpha

We analyzed the relation of osteoprotegerin (OPG) with insulin sensitivity, lipid profile, serum glutamic pyruvic transaminase (SGPT), adipocytokines, and C-reactive protein (CRP) in obese and non-obese subjects.. In the study, 170 subjects (106 obese and 64 non-obese, sex ratio female/male=2.03) were included. Thirty-two obese subjects were reevaluated 6 months after the weight loss induced by bariatric surgery.. OPG did not differ between obese and non-obese subjects (respective mean values 5.17 and 4.96 pmol/l) or according to gender, but was positively correlated with age (P<0.0001 for both groups). OPG was statistically higher in 18 obese diabetic subjects compared with non-diabetics (P=0.03). After adjustment for age, no significant correlation was found between OPG and body mass index (BMI), waist, systolic and diastolic blood pressure, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, leptin, and adiponectin in both the obese and non-obese subjects. However, OPG was positively correlated with homeostasis model assessment (HOMA) index and SGPT levels in obese subjects at baseline (r=0.295, r=0.20, P<0.05) and after adjustment for age (r=0.28, r=0.20, P<0.05). OPG was also significantly correlated with CRP; this correlation persisted after adjustment for age in obese subjects (r=0.30, P<0.01). In a multivariate analysis in the obese group, HOMA index and CRP were independent predictors of OPG while SGPT was not. Six months post-surgery, OPG did not change, despite a significant reduction in glucose, SGPT, cholesterol, triglycerides, CRP, and leptin values (P=0.02, P=0.006, P=0.007, P<0.001, P<0.001, P<0.001 respectively) and a significant increase in adiponectin and HDL values (P<0.001 for both variables).. Our results show that in obese subjects, OPG is not related to BMI. However, we describe new relationships between OPG and both HOMA index and CRP.

Topics: Adipokines; Adult; Alanine Transaminase; Bariatric Surgery; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Osteoprotegerin; Regression Analysis; Risk Factors; Triglycerides; Weight Loss

No mouse model is currently available where the induction of type 2 diabetes on an atherosclerotic background could be achieved without significant concomitant changes in plasma lipid levels. We crossbred 2 genetically modified mouse strains to achieve a model expressing both atherosclerosis and characteristics of type 2 diabetes. For atherosclerotic background we used low-density lipoprotein receptor-deficient mice synthetizing only apolipoprotein B100 (LDLR(-/-) ApoB(100/100)). Diabetic background was obtained from transgenic mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells. Thorough phenotypic characterization was performed in 6- and 15-month-old mice on both normal and high-fat Western diet. Results indicated that IGF-II transgenic LDLR(-/-)ApoB(100/100) mice demonstrated insulin resistance, hyperglycemia, and mild hyperinsulinemia compared with hypercholesterolemic LDLR(-/-)ApoB(100/100) controls. In addition, old IGF-II/LDLR(-/-)ApoB(100/100) mice displayed significantly increased lesion calcification, which was more related to insulin resistance than glucose levels, and significantly higher baseline expression in aorta of several genes related to calcification and inflammation. Lipid levels of IGF-II/LDLR(-/-)ApoB(100/100) mice did not differ from LDLR(-/-)ApoB(100/100) controls at any time. In conclusion, type 2 diabetic factors induce increased calcification and lesion progression without any lipid changes in a new mouse model of diabetic macroangiopathy.

Topics: Animals; Apolipoproteins B; Atherosclerosis; Blood Glucose; Calcinosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Models, Animal; Hypercholesterolemia; Hyperglycemia; Insulin Resistance; Insulin-Like Growth Factor II; Lipids; Mice; Mice, Inbred C57BL; Mice, Transgenic; Osteoprotegerin; Receptors, LDL

We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women.

Topics: Adult; Blood Glucose; Body Mass Index; Case-Control Studies; Fasting; Female; Health Status; Humans; Insulin Resistance; Leptin; Obesity; Osteoprotegerin; Premenopause

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

Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of nuclear factor I masculine B ligand. Osteoprotegerin has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. Recently, OPG has been proposed as a link molecule between osteoporosis and arterial calcification, but the relationship between circulating OPG levels and cardiovascular disease in human populations is unclear. Thus, the aim of this study was to investigate the relationship between circulating OPG levels and cardiovascular risk factors in healthy Korean women. The subjects were 286 women aged 37 to 73 (mean +/- SD, 51.5 +/- 6.9 years). We examined blood pressure, body mass index, and waist-to-hip ratio. Serum concentrations of OPG were determined by enzyme-linked immunosorbent assay. Fasting plasma glucose levels, serum lipid profiles, insulin levels, and serum follicle-stimulating hormone (FSH) levels were determined by standard methods and homeostasis model assessment of insulin resistance was calculated. We observed a significant association between serum OPG levels and age, waist-to-hip ratio, total cholesterol, low-density lipoprotein cholesterol, and FSH levels (P < .05). Among the metabolic components, the older, obese, and hypercholsterolemic subjects had higher serum OPG levels (P < .05). However, no significant relationship was found between serum OPG levels and blood pressure and fasting plasma glucose levels. We found that mean serum OPG levels were about 11% greater in postmenopausal women (mean +/- SD, 1358.5 +/- 380.0 pg/mL) than in premenopausal women (mean +/- SD, 1228.8 +/- 407.7 pg/mL, P < .001). In multiple regression analysis with OPG as the dependent variable, serum FSH and low-density lipoprotein cholesterol levels were the significant predictor for serum OPG level (R(2) = 0.051, P < .05). In conclusion, our results show that circulating OPG levels are partly associated with cardiovascular risk factors and menopausal status in healthy Korean women. Out findings suggest that OPG may be an important paracrine factor of cardiovascular disease in the female population.

Topics: Adult; Age Factors; Aged; Cardiovascular Diseases; Carrier Proteins; Cholesterol; Cholesterol, LDL; Female; Glycoproteins; Humans; Insulin Resistance; Membrane Glycoproteins; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; Waist-Hip Ratio

We investigated the relationship between insulin resistance and serum osteoprotegerin (OPG) levels in healthy obese subjects and healthy lean controls.. Fifty obese subjects (age: 31+/-8 years) and 24 lean controls (age: 30+/-7 years) were included in the study. We used the homeostasis model assessment for insulin resistance (HOMA-IR) index as the index of insulin resistance. OPG levels were measured with the commercial ELISA kit. Obese subjects were studied in three groups: Group I (n = 25) HOMA-IR index < 2.24, Group II (n = 13) index 2.24-3.59, Group III (n = 12) index > 3.59. Group IV (n = 24) was the lean controls with HOMA-IR index < 2.24.. Obese subjects with increased insulin resistance (Group III) had lower OPG values than other groups (11.88+/-7.43 pg/ml, 16.39+/-6.39 pg/ml, 17.37+/-9.61 pg/ml, and 18.1+/-6.65 pg/ml, respectively; Group I versus Group III p = 0.036; Group III versus Group IV p = 0.012). We also found significant inverse correlations between OPGc (corrected for BMI) and fasting glucose (r = -0.325, p = 0.005), fasting insulin (r = -0.404, p = 0.0001) as well as HOMA-IR (r = -0.428, p = 0.0001). Increased fibrinogen level was found in Group III than Group IV (9.32+/-1.97 micromol/l versus 7.47+/-1.65 micromol/l, respectively; p = 0.005). In conclusion, insulin resistance in obesity is associated with decreased serum OPG levels and increased fibrinogen levels. The relationship between serum OPG levels and HOMA-IR may provide an insight into vascular endothelial dysfunction in obesity.

Topics: Adult; Blood Glucose; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Fibrinogen; Glycoproteins; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Obesity; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

We examined the association between serum osteoprotegerin (OPG) levels, systemic inflammation and arterial stiffness in normal and diabetic patients.. The study subjects comprised 49 newly diagnosed diabetic patients and 72 age- and sex-matched normal glucose controls. Anthropometric parameters, blood pressure, fasting blood glucose (FBG), lipid profiles, serum OPG, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and brachial-ankle pulse wave velocity (baPWV) were measured.. Serum OPG levels (6.1 +/- 1.4 vs. 5.4 +/- 1.3 pmol/l, P = 0.011) and baPWV (1562 +/- 354 vs. 1399 +/- 257 cm/s, P = 0.004) were significantly higher in the diabetic group than in the normal glucose group. Serum OPG levels in normal and diabetic patients correlated significantly with systolic blood pressure (r = 0.20, P = 0.035), FBG (r = 0.30, P = 0.002), right baPWV (r = 0.22, P = 0.021), left baPWV (r = 0.26, P = 0.006), homeostasis model assessment insulin resistance (HOMA-IR) (r = 0.19, P = 0.045), IL-6 (r = 0.32, P = 0.001) and hsCRP (r = 0.21, P = 0.027) after adjusting for age and sex. Multiple regression analysis showed that serum OPG level was significantly associated with age, FBG, IL-6, systolic blood pressure, triglyceride and hsCRP (R(2) = 0.299).. In summary, serum OPG and baPWV levels are elevated in diabetic patients and serum OPG levels are significantly associated with inflammation and arterial stiffness.

Topics: Biomarkers; Blood Glucose; Brachial Artery; C-Reactive Protein; Case-Control Studies; Diabetes Mellitus; Female; Glycoproteins; Humans; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Lipids; Male; Middle Aged; Osteoprotegerin; Pulsatile Flow; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Regression Analysis; Signal Processing, Computer-Assisted; Systole; Triglycerides