Relationships between Circulating Biomarkers and Body Composition Parameters in Patients with Metabolic Syndrome: A Community-Based Study.

Metabolic syndrome (MetS) is a complex disease involving multiple physiological, biochemical, and metabolic abnormalities. The search for reliable biomarkers may help to better elucidate its pathogenesis and develop new preventive and therapeutic strategies. In the present population-based study, we looked for biomarkers of MetS among obesity- and inflammation-related circulating factors and body composition parameters in 1079 individuals (with age range between 18 and 80) belonging to an ethnically homogeneous population. Plasma levels of soluble markers were measured by using ELISA. Body composition parameters were assessed using bioimpedance analysis (BIA). Statistical analysis, including mixed-effects regression, with MetS as a dependent variable, revealed that the most significant independent variables were mainly adipose tissue-related phenotypes, including fat mass/weight (FM/WT) [OR (95% CI)], 2.77 (2.01-3.81); leptin/adiponectin ratio (L/A ratio), 1.50 (1.23-1.83); growth and differentiation factor 15 (GDF-15) levels, 1.32 (1.08-1.62); inflammatory markers, specifically monocyte to high-density lipoprotein cholesterol ratio (MHR), 2.53 (2.00-3.15), and a few others. Additive Bayesian network modeling suggests that age, sex, MHR, and FM/WT are directly associated with MetS and probably affect its manifestation. Additionally, MetS may be causing the GDF-15 and L/A ratio. Our novel findings suggest the existence of complex, age-related, and possibly hierarchical relationships between MetS and factors associated with obesity.

Scoliosis and skeletal muscle mass are strongly associated with low back pain-related disability in humans: An evolutionary anthropology point of view.

OBJECTIVES: To clarify the potential risk factors and etiology of low back pain (LBP)-related disability, including structural changes of the spine (spinal scoliosis) and body composition components in a population with a high prevalence of LBP. METHODS: In this cross-sectional study, two self-reported validated questionnaires were used to collect back pain and disability data in an ethnically homogeneous family-based population sample (N = 1078). The scoliosis angle of trunk rotation was measured by a scoliometer on three spinal levels while the patient was bent forward. Body composition parameters, including relative to weight (WT), fat, relative skeletal muscle mass (SMM/WT), and total body water were determined by bioelectrical impedance analysis. Statistical analysis was conducted, accounting for the familial composition of the sample. RESULTS: The mixed multiple regression analyses with several LBP-related phenotypes as dependent variables consistently showed significant independent associations with scoliosis and SMM/WT, irrespective of other covariates. The odds ratios (OR)/95% CI for scoliosis ranged between 1.40 (1.19-1.64) and 1.51 (1.27-1.80), and from 0.61(0.51-0.72), to 0.71(0.58-0.87) for SMM/WT, depending on the LBP phenotype. The genetic components of the respective correlations between the LBP-phenotypes and scoliosis or SMM/WT were negligible. CONCLUSIONS: The associations between LBP-related conditions and postured scoliosis and SMM/WT were consistent and significant and therefore may serve as markers in predicting the development of LBP-related disability. We interpret the origin of these correlations as the evolutionary event due to the imperfect spine anatomy adaptation to a vertical posture resulting from a quick transition to bipedalism from a quadrupedal ancestor.

Growth and differentiation factor 15 is a biomarker for low back pain-associated disability.

The development of low back pain (LBP) is often associated with obesity and sarcopenia. However, the mechanisms of this association remain unclear. To clarify this, we measured circulating levels of a selected panel of soluble factors, presumably involved in obesity and sarcopenia pathogenesis, and correlated them with several LBP-related characteristics, taking into account body composition and other relevant covariates. In the cross-sectional study of 1078 individuals, we collected data on self-reported LBP, body composition (including fat and skeletal muscle mass) assessed by the bioimpedance method and anthropometrically, and measured plasma levels of several cytokines by ELISA. In the statistical analysis, we took into account familial composition of the sample and possible putative genetic effects. We report that LBP-affected individuals were significantly older, with increased obesity and decreased skeletal mass, respectively, compared with the non-affected group. In univariate analyses, plasma concentrations of Growth and differentiation factor 15 (GDF-15), leptin, chemerin and follistatin were found significantly elevated in the LBP-affected groups (with or without sciatic pain) and were highly significantly (p < 0.001) associated with other LBP-related phenotypes, specifically, disease duration, disability and physician consults. However, after adjustment for one another, age, sex, body composition and putative genetic factors, the only associations between GDF-15 and LBP disability and medical consulting phenotypes, remained significant. In conclusion, we report for the first time, a significant and independent association between plasma GDF-15 concentrations and LBP-associated disability. Longitudinal studies are needed to determine whether GDF-15 could be a novel therapeutic target for prevention and/or treatment of LBP.

Analysis of the Associations of Measurements of Body Composition and Inflammatory Factors with Cardiovascular Disease and Its Comorbidities in a Community-Based Study.

The associations of cardiovascular disease (CVD) with comorbidities and biochemical and body composition measurements are repeatedly described but have not been studied simultaneously. In the present cross-sectional study, information on CVD and comorbidities [type 2 diabetes mellitus (T2DM), hypertension (HTN), and hyperlipidemia (HDL)], body composition, levels of soluble markers, and other measures were collected from 1079 individuals. When we examined the association of each comorbidity and CVD, controlling for other comorbidities, we observed a clear pattern of the comorbidity-related specific associations with tested covariates. For example, T2DM was significantly associated with GDF-15 levels and the leptin/adiponectin (L/A) ratio independently of two other comorbidities; HTN, similarly, was independently associated with extracellular water (ECW) levels, L/A ratio, and age; and HDL was independently related to age only. CVD showed very strong independent associations with each of the comorbidities, being associated most strongly with HTN (OR = 10.89, 6.46-18.38) but also with HDL (2.49, 1.43-4.33) and T2DM (1.93, 1.12-3.33). An additive Bayesian network analysis suggests that all three comorbidities, particularly HTN, GDF-15 levels, and ECW content, likely have a main role in the risk of CVD development. Other factors, L/A ratio, lymphocyte count, and the systemic inflammation response index, are likely indirectly related to CVD, acting through the comorbidities and ECW.

Elevated circulating levels of IL-34 are strongly associated with osteoporosis.

In this cross-sectional study, we observed a strong, age-independent association of circulating interleukin-34 (IL-34) levels with osteoporosis. PURPOSE: The reported capacity of IL-34 to induce and enhance osteoclastogenesis suggests its potential involvement in the pathogenesis of osteoporosis. Our study aimed to evaluate whether there is an association between IL-34 expression and osteoporosis. METHODS: We enrolled 30 women with osteoporosis and 230 age-matched non-osteoporotic women as a control group. Osteoporosis diagnosis was based on dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. Body composition parameters were assessed by the bioimpedance method. Plasma IL-34 levels were measured by ELISA. RESULTS: In comparison with the control group, the mean plasma IL-34 levels were significantly higher in osteoporotic women (164.61 ± 36.40 pg/ml vs. 665.43 ± 253.67 pg/ml, p = 0.0002), whereas basal metabolic rate (BMR) was significantly lower (1422.03 ± 6.80 kcal vs. 1339.39 ± 17.52 kcal, p = 0.00007). Both variables remained statistically significant after adjustment for age (p < 0.001). We did not observe correlations between plasma IL-34 levels and body composition parameters in osteoporotic and control groups. Multiple logistic regression analysis with osteoporosis status as a dependent variable clearly showed that age, BMR and IL-34 levels were independently and significantly associated with osteoporosis. The calculated odds ratios (OR) were 1.66 (95% CI = 1.16-2.38) for IL-34 levels and 0.22 (95% CI = 0.07-0.65) for BMR. CONCLUSION: The significant (fourfold) elevation of IL-34 plasma levels in osteoporosis patients suggests that circulating IL-34 could be used as a biomarker for osteoporosis.

Pro-Inflammatory Biomarkers Combined with Body Composition Display a Strong Association with Knee Osteoarthritis in a Community-Based Study.

Knee osteoarthritis (KOA) is one of the most common progressive, age-dependent chronic degenerative joint diseases. KOA often develops as a result of a gradual articular cartilage loss caused by its wear and tear. Numerous studies suggest that the degradation of the knee joint involves inflammatory components. This process is also associated with body composition, particularly being overweight and muscle mass loss. The present study aimed to search for novel circulating KOA inflammatory biomarkers, taking into account body composition characteristics. To this aim, we recruited 98 patients diagnosed and radiologically confirmed with KOA and 519 healthy controls from the Arab community in Israel. A panel of soluble molecules, related to inflammatory, metabolic, and musculoskeletal disorders, was measured by ELISA in plasma samples, while several body composition parameters were assessed with bioimpedance analysis. Statistical analysis, including multivariable logistic regression, revealed a number of the factors significantly associated with KOA, independently of age and sex. The most significant independent associations [OR (95% CI)] were fat body mass/body weight index-1.56 (1.20-2.02), systemic immune-inflammation index-4.03 (2.23-7.27), circulating vaspin levels-1.39 (1.15-1.68), follistatin/FSTL1 ratio-1.32 (1.02-1.70), and activin A/FSTL1 ratio-1.33 (1.01-1.75). Further clinical studies are warranted to confirm the relevance of these KOA-associated biological factors. Hereafter, they could serve as reliable biomarkers for KOA in the general human population.

Deciphering the Causal Relationships Between Low Back Pain Complications, Metabolic Factors, and Comorbidities.

PURPOSE: Low back pain (LBP) is one of the major disabling health conditions in aging societies presenting significant cost burdens to health and social care systems. Its complications and associated disability are often accompanied by mental disorders, metabolic comorbidities, changed body composition, and inflammation. However, their mutual relationships in LBP-associated disability remain unclear. METHODS: In the present case-control study, a self-report validated questionnaire was used to collect LBP disability data in an ethnically homogeneous Israeli Arab sample (489 males and 589 females). Body composition parameters were assessed through bioelectrical impedance analysis and plasma levels of soluble markers by EISA. Comorbidity status was assessed in personal interview and from the individual medical files. RESULTS: Our mixed multiple regression analysis identified that GDF-15 (ß = 0.160, p = 2.95×10-8), vaspin (ß = 0.085, p = 0.003), follistatin (ß = 0.076, p = 0.001), extracellular water (ß = 0.096, p = 0.001), waist hip ratio (ß = 0.072, p = 0.009), mental disorders (ß = 0.077, p = 0.001), and metabolic comorbidities (ß = 0.059, p = 0.02) were significantly associated with LBP disability scores, when controlling for age and sex effects. Additive Bayesian network modelling further suggests that LBP disability appears to be directly influenced by age, sex, GDF-15, and extracellular water, and indirectly by mental and metabolic disorders, waist-hip ratio, and follistatin. LBP, in turn, seems to affect the vaspin levels directly. CONCLUSION: Our data suggest the existence of a complex, age-associated, and probably hierarchical, relationship between LBP disability and mental and metabolic disorders, inflammation-related soluble markers, and body composition parameters.

The search for systemic biomarkers for monitoring degenerative lumbar spinal disorders.

Objectives: In our previous study, we reported that low back pain (LBP) severity and disability significantly correlate with body composition and several blood biochemical factors. Herein, we tested the hypothesis that these covariates are associated with anatomical deformations of the lumbar spine, in particular, radiographic facet joint osteoarthritis (FJOA) and lumbar disc degeneration (LDD) features important contributors to LBP. Methods: CT and MRI images of the lumbar spine were obtained from 200 individuals suffering from LBP-sciatica. We examined the FJOA and total LDD score - the sum of the scores of the three radiographic features (intervertebral disc herniation, osteophythosis and spondylolisthesis) at the L1 - S1 vertebral levels. By implementing a bioelectrical impedance analysis, we assessed the participants for body composition, specifically, extracellular water (ECW). Plasma levels of growth and differentiation factor 15 (GDF-15) and visceral adipose tissue-derived serine protease inhibitor (vaspin), were detected by ELISA. Results: By conducting a series of multivariable regression analyses, we report that the circulating levels of GDF-15, vaspin, and ECW are significantly and independently associated with FJOA scores [ßGDF15 â€‹= â€‹0.38 â€‹± â€‹0.08, p â€‹= â€‹0.0001; ßVASPIN â€‹= â€‹0.36 â€‹± â€‹0.07, p â€‹= â€‹0.000004; ßECW â€‹= â€‹0.24 â€‹± â€‹0.07, p â€‹= â€‹0.002]. The levels of GDF-15 (ߠ​= â€‹0.30 â€‹± â€‹0.10, p â€‹= â€‹0.007) and ECW (ߠ​= â€‹0.20 â€‹± â€‹0.09, p â€‹= â€‹0.03) were also found significantly associated with the LDD scores. Conclusion: The obtained new data suggest that GDF-15, vaspin and ECW may serve as biomarkers for FJOA and LDD phenotypes.

Circulating Levels of Visceral Adipose Tissue-Derived Serine Protease Inhibitor (Vaspin) Appear as a Marker of Musculoskeletal Pain Disability.

Musculoskeletal pain (MSP), specifically low back pain (LBP), is often associated with several adipose tissue-derived cytokines (adipokines) and body composition, but their correlations with the LBP-related disability/severity phenotypes remain poorly understood. In this cross-sectional study, two self-reported validated questionnaires were used to collect back pain and disability data in an ethnically homogeneous family-based population sample (N = 1078). Plasma levels of relatively new adipokines, vaspin and adipsin, were detected by ELISA. Body composition parameters, including fat, skeletal muscle mass, extracellular water (ECW), and others were assessed through bioelectrical impedance analysis (BIA) technology. Statistical analysis was conducted, accounting for the familial composition of the sample. The multiple regression analyses with four LBP-related phenotypes as dependent variables consistently showed, for the first time, the significant associations with vaspin levels, regardless of other covariates. The odds ratios (OR)/SD ranged between 1.24 (95%CI = 1.03-1.50) and 1.33 (95%CI = 1.07-1.64), depending on the LBP phenotype. Among the tested body composition covariates, only ECW levels displayed consistent and highly significant associations with all tested LBP phenotypes (OR from 1.43, 95%CI = 1.14-1.79 to 1.68, 95%CI = 1.26-2.24). The results clearly suggest that circulating concentrations of vaspin and ECW levels could serve as biomarkers of MSP/LBP severity and complications.

Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.

BACKGROUND: Thoracic and abdominal aortic aneurysms and dissection often develop in hypertensive elderly patients. At higher risk are smokers and those who have a family history of aortic aneurysms. In most affected families, the aortic aneurysms and dissection is inherited in an autosomal dominant manner with decreased penetrance and variable expressivity. Mutations at two chromosomal loci, TAA1 at 11q23 and the TAA2 at 5q13-14, and eight genes, MYLK, MYH11, TGFBR2, TGFBR1, ACTA2, SMAD3, TGFB2, and MAT2A, have been identified as being responsible for the disease in 23% of affected families. RESULTS: Herein, we inform on the clinical, genetic and pathological characteristics of nine living and deceased members of a large consanguineous Arab family with thoracic aortic aneurysm and dissection who carry a missense mutation c.4471G > T (Ala1491Ser), in exon 27 of MYLK gene. We show a reduced kinase activity of the Ala1491Ser protein compared to wildtype protein. This mutation is expressed as aortic aneurysm and dissection in one of two distinct phenotypes. A severe fatal and early onset symptom in homozygous or mild late onset in heterozygous genotypes. CONCLUSIONS: We found that MYLK gene Ala1491Ser mutation affect the kinase activity and clinically, it presents with vascular aneurysms and dissection. We describe a distinct genotype phenotype correlation where; heterozygous patients have mild late onset and incomplete penetrance disease compared with the early onset severe and generally fatal outcome in homozygous patients.