leptin and Spondylitis--Ankylosing

Various studies have researched the serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis (AS), but the results were inconclusive. The purpose of this study was to systematically evaluate the correlations between serum levels of these adipokines and AS.. Electronic databases were retrieved to search relevant publications. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Cochrane Q test and I. A total of sixteen articles were included. Meta-analysis results indicated no statistical differences between AS patients and normal controls in serum leptin and adiponectin levels (leptin, SMD=0.829, 95% CI=-0.116 to 1.774, p=0.085; adiponectin, SMD=0.460, 95% CI=-0.004 to 0.924, p=0.052). However, AS patients had higher serum resistin levels than controls (SMD=1.413, 95% CI=0.294 to 2.531, p=0.013). Subgroup analyses suggested that Asian and African AS patients as well as patients aged <40years had higher serum leptin and resistin levels when compared to controls. Serum adiponectin levels were higher in AS patients compared to controls in subgroup of age ≥40, and serum resistin levels in subgroup of BMI ≥25. Measurement method was a source of heterogeneity for resistin. Publication bias was not observed and the robustness of study results was confirmed by sensitivity analysis.. Serum resistin, but not leptin or adiponectin levels may be closely associated with the development of AS.

Topics: Adiponectin; Age Factors; Asian People; Black People; Disease Progression; Humans; Leptin; Resistin; Risk; Spondylitis, Ankylosing

Leptin is an adipokine that has several effects on metabolism and immune system in patients with ankylosing spondylitis (AS). The present investigations of the relationship between plasma/serum leptin levels and AS are contradictory. To derive a more precise estimation on the plasma/serum leptin levels in AS patients and related factors, a meta-analysis was performed.. Published literature that compares plasma/serum leptin levels between AS group and control group from PubMed, Embase, Cochrane Library and other databases were searched. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analyses. Statistical heterogeneity within studies was examined by the Q statistic.. A total of eight studies including 391 AS patients and 293 healthy controls were finally included in the meta-analysis. No significant differences in plasma/serum leptin levels was found between AS patients and healthy controls when all studies were pooled into the meta-analysis (pooled SMD = 0.384, 95% CI = -1.522 to 0.753). Meanwhile, subgroup analyses by gender also showed no significant differences in plasma/serum leptin levels between case group and controls.. There is no significant difference in plasma/serum leptin levels between AS patients and controls.

Topics: Adipokines; Case-Control Studies; Humans; Leptin; Plasma; Serum; Spondylitis, Ankylosing

The objective of this study was to examine whether adding biomarkers to routine clinical parameters improves prediction of radiographic spinal progression in axial spondyloarthritis.. One hundred and seventeen patients with ankylosing spondylitis who completed the Effects of NSAIDs on RAdiographic Damage in Ankylosing Spondylitis (ENRADAS) trial were included. Radiographic spinal progression was defined as worsening of the modified Stoke Ankylosing Spondylitis Spine Score by ⩾2 points after 2 years. A clinical prediction model was constructed out of baseline syndesmophytes, elevated CRP, cigarette smoking and male sex. The following serum biomarkers were measured at baseline by ELISA: MMP3, VEGF, calprotectin, leptin, high molecular weight adiponectin, osteoprotegerin, sclerostin, N-terminal telopeptide, procollagen type II N-terminal propeptide and serum amyloid A.. Repeated cross-validation analyses revealed one biomarker combination with potential added predictive value in addition to the clinical model: leptin + high molecular weight adiponectin + VEGF. This biomarker combination showed an area under the curve (AUC)Biomarkers = 0.731 (95% CI: 0.614, 0.848), which was numerically superior to the clinical model [AUCClinical = 0.665 (95% CI: 0.553, 0.776)]. A combination of clinical parameters + biomarkers showed an improved predictive value compared with the clinical model reflected by AUCClinical+Biomarkers = 0.768 (95% CI: 0.666, 0.871), though not statistically significant (P = 0.051). However, by considering the part of the receiver operating characteristic curve with a specificity ⩾75% resulting in partial AUC (pAUC), the improvement becomes significant (pAUCClinical+Biomarkers = 0.119; pAUCClinical = 0.053; P = 0.01).. Biomarkers show potential to improve the prediction of radiographic spinal progression in axial spondyloarthritis when used in addition to the clinical parameters, though the added value seems to be rather small.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Disease Progression; Female; Humans; Inflammation Mediators; Leptin; Male; Middle Aged; Predictive Value of Tests; Radiography; ROC Curve; Severity of Illness Index; Spine; Spondylitis, Ankylosing; Vascular Endothelial Growth Factor A

Previous research indicates a role of adipokines in inflammation and osteogenesis. Hence adipokines might also have a pathophysiological role in inflammation and new bone formation in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the role of adipokine serum levels as predictors of radiographic spinal progression in patients with AS.. A total of 120 patients with definite AS who completed a 2-year follow up in the ENRADAS trial were included in the current study. Radiographic spinal progression was defined as: (1) worsening of the modified Stoke Ankylosing Spondylitis spine (mSASSS) score by ≥2 points and/or (2) new syndesmophyte formation or progression of existing syndesmophytes after 2 years. Serum levels of adipokines (adiponectin (APN) and its high molecular weight form (HMW-APN), chemerin, leptin, lipocalin-2, omentin, resistin, visfatin) were measured using enzyme-linked immunosorbent assays.. There was a significant association between radiographic spinal progression and both leptin and HMW-APN. Baseline serum levels of both adipokines were lower in patients who showed radiographic spinal progression after 2 years. This association was especially evident in men; they had generally lower leptin and HMW-APN serum levels as compared to women. The inverse association between adipokines and radiographic spinal progression was confirmed in the logistic regression analysis: the odds ratios (OR) for the outcome "no mSASSS progression ≥2 points" were 1.16 (95% CI 1.03 to 1.29) and 1.17 (95% CI 0.99 to 1.38), for leptin and HMW-APN, respectively; for "no syndesmophyte formation/progression" the respective OR were 1.29 (95% CI 1.11 to 1.50) and 1.18 (95% CI 0.98 to 1.42), adjusted for the presence of syndesmophytes at baseline, C-reactive protein at baseline, sex, body mass index (BMI), non-steroidal anti-inflammatory drugs intake score over 2 years, and smoking status at baseline.. Serum leptin and HMW-APN predict protection from spinal radiographic progression in patients with AS. Women generally have higher leptin and HMW-APN serum levels that might explain why they have less structural damage in the spine as compared to male patients with AS.. EudraCT: 2007-007637-39. ClinicalTrials.gov, NCT00715091 . Registered on 14 July 2008.

Topics: Adiponectin; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Disease Progression; Female; Humans; Leptin; Male; Middle Aged; Spondylitis, Ankylosing

To analyse the influence of adipokines on attaining the clinical outcomes in patients with axial spondyloarthritis (axSpA) treated with TNF inhibitors (TNFi), and then, to investigate the association of patients' characteristics and adipokine concentrations.. This was a longitudinal study including 110 patients with axSpA who were initiated at TNFi and were followed-up for 6 months (m). Disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline and at 6 m of treatment. Clinical outcomes at 6 m of treatment were defined as remission (ASDAS <1.3) and the attainment of low disease activity (LDA; ASDAS<2.1). Leptin and adiponectin concentrations were measured in serum samples collected at baseline and after 6 m.. Both leptin and adiponectin were constitutively elevated in female axSpA patients. At time of TNFi initiation, leptin concentrations were higher in patients with high body mass index (overweight or obese). On the contrary, adiponectin was higher in normalweight patients. After 6 m of TNFi treatment, 24% of patients attained remission. They had significant lower leptin concentration at baseline compared with patients who did not attain remission. Furthermore, this difference remained significant after 6 m of treatment meaning that TNFi did not modify adipokine concentration. Similar results were found considering LDA as the clinical outcome, obtained in 48% of the patients.. The present study showed that low leptin concentrations were associated with attaining clinical outcomes in axSpA patients treated with TNFi. In addition, since leptin secretion by white adipocytes is enhanced during obesity and considering that TNFi do not seem to modulate its expression, obese patients should be encouraged to decrease BMI to attain a successful therapy.

Topics: Adiponectin; Female; Humans; Leptin; Longitudinal Studies; Obesity; Severity of Illness Index; Spondylarthritis; Spondylitis, Ankylosing; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha

There is limited information on the effect of black beans (BB) as a source of protein and resistant starch on the intestinal microbiota. The purpose of the present work was to study the effect of cooked black beans with and without high fat and sugar (HF + S) in the diet on body composition, energy expenditure, gut microbiota, short-chain fatty acids, NF-κB, occluding and insulin signaling in a rat model and the area under the curve for glucose, insulin and incretins in healthy subjects. The consumption of BB reduced the percentage of body fat, the area under the curve of glucose, serum leptin, LPS, glucose and insulin concentrations and increased energy expenditure even in the presence of HF + S. These results could be mediated in part by modification of the gut microbiota, by increasing a cluster of bacteria in the Clostridia class, mainly

Topics: Animals; Body Fat Distribution; Butyrates; Clostridiales; Dietary Supplements; Endotoxemia; Energy Metabolism; Fabaceae; Gastrointestinal Microbiome; Glucose; Healthy Volunteers; Insulin Resistance; Leptin; Liver; Male; Models, Animal; Oxygenases; Rats, Wistar; Spondylitis, Ankylosing

Objective To identify correlations of the serum leptin, adiponectin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations with the clinical characteristics, presence of spinal syndesmophytes, and body composition in patients with ankylosing spondylitis (AS). Methods Forty-eight patients with AS were compared with 41 sex- and age-matched controls. Assessment included clinical characteristics and the presence of spinal syndesmophytes. The serum leptin, adiponectin, TNF-α, and IL-6 concentrations were determined. Body composition was evaluated using dual-energy X-ray absorptiometry. Results Patients with AS and controls had similar fat mass and lean mass. Patients with AS had higher serum TNF-α and leptin concentrations than controls (52.3 vs. 1.5 pg/mL and 17.2 vs. 9.0 µg/mL, respectively). The IL-6 and adiponectin concentrations were not significantly different between the two groups. Patients with syndesmophytes had higher leptin concentrations than those without syndesmophytes (22.1 vs. 10.9 µg/mL); this difference remained after adjustment for the body mass index. Conclusion Elevated leptin concentrations are associated with spinal radiographic damage in patients with AS and can serve as a biomarker. Future studies should evaluate whether leptin might be a potential target for treatments to avoid structural damage.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Body Composition; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Spine; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha

The immunomodulatory effects of adipokines have been extensively studied in rheumatic diseases, and there is a paucity of information regarding their effects on bone metabolism.The aim of this study was to investigate the relationships between serum adipokines levels and radiographic progression over 2 years in patients with ankylosing spondylitis (AS).In this preliminary longitudinal study, we prospectively recruited 20 consecutive male patients with AS and 11 gender- and age-matched healthy subjects. At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls. Radiographic progression was determined as the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression of ≥2 by comparing the baseline and 2-year follow-up radiographs.All AS patients were naive to TNF-α blockers at the enrollment and during the 2-year follow-up period and their median disease duration was 51.5 months. At the baseline, the serum resistin, TNF-α, and IL-6 levels were significantly higher in AS patients than in controls. At the 2-year follow-up, the median mSASSS of AS patients was found to be significantly increased from the baseline (8-10.5, P = .001) and 7 (35%) AS patients showed radiographic progression. In AS patients, the leptin and resistin levels were significantly higher at the 2-year follow-up than at the baseline. The baseline resistin levels and changes in leptin levels from the baseline to the 2-year follow-up were significantly higher in AS patients with radiographic progression than in those without radiographic progression (P = .002 and .024, respectively). The baseline resistin levels and the increase in leptin levels during the follow-up period significantly correlated with changes in mSASSS (ρ = 0.528 and 0.559, P = .017 and .01, respectively). No association between changes in serum adipokine levels and disease activity in AS patients was observed.Our findings suggest that leptin and resistin may contribute to the pathogenesis of new bone formation rather than to inflammatory processes and have the potential to be used as biomarkers of the structural outcome of AS.

Topics: Adaptor Proteins, Signal Transducing; Adipokines; Adiponectin; Adult; Biomarkers; Chemokines; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Longitudinal Studies; Male; Middle Aged; Resistin; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha

The aim of this study is to clarify the association between serum leptin levels and the presence of syndesmophytes in male patients with ankylosing spondylitis (AS). Seventy-two male patients with AS and 20 age-matched healthy male controls were included. Patients were stratified by the presence of syndesmophytes. Serum leptin levels were measured and adjusted for body mass index (BMI). In addition, bone-specific alkaline phosphatase (BALP), osteocalcin, and telopeptide of type I collagen were determined. Patients with syndesmophytes were associated with older age (p < 0.001), longer disease duration (p = 0.003), and higher BMI (p = 0.038). Serum leptin levels and leptin per BMI (leptin/BMI) ratio were not different between AS patients and healthy controls. However, serum leptin/BMI ratio was significantly higher in patients with syndesmophytes compared to those without (p = 0.010). In multivariate analysis, higher serum leptin/BMI ratio remained significantly associated with the presence of syndesmophytes (p = 0.029). Moreover, serum leptin/BMI ratio was positively correlated with serum BALP (γ = 0.279, p = 0.039). However, there was no significant association between serum leptin/BMI ratio and bone mineral density. Serum leptin levels are elevated in male AS patients with syndesmophytes and were found to be correlated with bone formation marker, suggesting a potential role of leptin in new bone formation in AS.

Topics: Adult; Alkaline Phosphatase; Biomarkers; Body Mass Index; Bone Density; Case-Control Studies; Cross-Sectional Studies; Humans; Leptin; Lumbar Vertebrae; Male; Radiography; Spondylitis, Ankylosing

Topics: Adult; Culture Media, Conditioned; Female; Gene Expression; Humans; Interleukin-6; Leptin; Leukocytes, Mononuclear; Male; RNA, Messenger; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha

This study was performed to investigate whether leptin mRNA expression is increased from peripheral blood mononuclear cells (PBMCs) of patients with active ankylosing spondylitis (AS) and whether it stimulates the production of pro-inflammatory cytokines.. Twenty patients with active AS were enrolled and their Bath AS disease activity index (BASDAI) and levels of acute phase reactants were measured. Leptin, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha mRNA expressions and their protein productions were determined in PBMCs of patients with AS using semi-quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Then, the results were compared with those from 20 healthy controls, as were clinical and laboratory parameters reflecting disease activity. The changes of pro-inflammatory cytokine productions from PBMCs in response to leptin stimulation were also determined.. Leptin, IL-6 and TNF-alpha mRNA expressions of PMBCs from patients with AS were significantly higher than controls. Similar significances were also found in the measurements for leptin and cytokine levels of supernatants, and leptin levels correlated well with IL-6 expression (r=0.871, p<0.001) and BASDAI (r=0.691, p<0.001) in patients with AS. Stimulation of PBMCs by exogenous leptin significantly increased the production of IL-6 and TNF-alpha in PBMCs from patients with AS in a dose-dependent fashion and these increases were much exacerbated compared to controls.. Our results shows that leptin production is increased and its stimulation of PBMCs significantly increased the production of pro-inflammatory cytokines in patients with active AS, suggesting its pro-inflammatory effect in pathogenesis of AS.

Topics: Adult; Female; Gene Expression; Health Status; Humans; Interleukin-6; Leptin; Leukocytes, Mononuclear; Male; RNA, Messenger; Severity of Illness Index; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha; Young Adult

The aim of this study was to compare the effect of chronic inflammation on insulin resistance, serum leptin levels, and body composition (BC) in patients with ankylosing spondylitis (AS) and healthy controls. Twenty-eight AS patients and 17 healthy controls were included in this study. Subjects with hypertension, diabetes, hyperlipidemia, and obesity were excluded. Acute phase reactants and serum levels of glucose, insulin, lipids, and leptin were studied. BC was determined anthropometrically and by foot-to-foot body fat analyzer (BIA, bioelectrical impedance analysis). Quantitative insulin-sensitivity check index, homeostasis model assessment for insulin resistance, and McAuley indices were calculated. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Age, sex distribution, smoking status, serum lipids, insulin concentrations, and insulin resistance indices were comparable between AS patients and controls (p > 0.05). However, acute phase reactants were significantly higher and leptin levels were significantly lower in the AS patients than in controls (p < 0.05). Fat percent assessed by both BIA and anthropometrical methods was lower in the male and female AS patients than in controls, and this reduced fat level reached statistical significance for men (p < 0.05). There were significant correlations between percent body fat, body mass index, leptin, age, and BASMI (p < 0.05; r = 0.6, 0.75, 0.35, -0.41, respectively). On the other hand, body fat percent, waist-to-hip ratio, C-reactive protein, and BASMI were significantly correlated with serum leptin levels (p < 0.05; r = 0.75, -0.42, -0.52, -0.47, respectively). Chronic inflammatory condition in AS may be responsible for the reduced body fat content and lower circulating leptin concentrations. Insulin levels and insulin resistance indices seem similar in patients and controls in the absence of classic vascular risk factors.

Topics: Adult; Body Composition; Body Mass Index; C-Reactive Protein; Case-Control Studies; Female; Humans; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Spondylitis, Ankylosing