Lack of association between serum apelin levels and sarcopenia in elderly malnourished subjects.

OBJECTIVE: Sarcopenia is a condition characterized by muscle mass loss. Skeletal muscle is capable of producing and secreting different molecules called myokines, and apelin is one of them. The literature contains contradictory data on the relationship between apelin and sarcopenia. We decided to investigate the role of apelin in sarcopenia in subjects with disease-related malnutrition (DRM), a group of patients with a high rate of sarcopenia. PATIENTS AND METHODS: 83 elderly patients with DRM assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria were included in the study, with a mean age of 69.9±3.8 years. Anthropometric data, muscle mass by ultrasound at the rectus femoris quadriceps (RFQ) level, bioimpedance [skeletal muscle mass (SMM), appendicular SMM (aSMM) and aSMM index (aSMMI)], dynamometry, biochemical parameters, dietary intake, circulating apelin levels were determined in all patients. RESULTS: a total of 33 patients (37.9%) were diagnosed with sarcopenia, while 54 patients did not present sarcopenia (60.1%). Body weight (-5.5±2.0 kg, p=0.01), calf circumference (-1.9±0.2 cm, p=0.02), phase angle (-0.6±0.2º, p=0.01), reactance (-6.8±2.3 Ohms, p=0.03), resistance (-38.8±12.3 Ohms, p=0.04), SMM (-2.2±0.3 kg, p=0.04), aSMM (-2.2±0.2 kg, p=0.03) and aSMMI (-0.6±0.2 kg, p=0.02), dominant muscle area (-0.6±0.2 cm2, p=0.04), dominant Y axis (-0.4±0.1 cm, p=0.03), dominant X/Y axis (1.1±0.3 cm, p=0.04), strength (-5.1±1.3 kg, p=0.01), albumin (-0.9±0.1 g/dl, p=0.02) and prealbumin (-4.6±0.7 mg/dl, p=0.02) were worse in patients with sarcopenia than non-sarcopenic patients. Circulating apelin levels were similar in both groups. No significant correlation of apelin levels was detected, either with bioimpedance data or with muscle ultrasonography data. The multivariant analysis did not detect a significant association of apelin with the presence of sarcopenia. CONCLUSIONS: Our study shows a lack of association between apelin and sarcopenia in elderly malnourished patients.

Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS-based untargeted metabonomics.

Background: Untargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics. Methods: In this nested case-control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia. Results: In comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711-0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598-0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587-0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, "purine metabolism"; "parathyroid hormone synthesis, secretion and action"; "choline metabolism in cancer"; and "tuberculosis". Conclusion: The current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.

Lower serum creatinine to cystatin C ratio associated with increased incidence of frailty in community-dwelling elderly men but not in elderly women.

BACKGROUND: Sarcopenia has been reported to play an important role in frailty syndrome. The serum creatinine/serum cystatin C ratio (Scr/Cys C ratio) has recently been recognized as a valuable indicator for assessing sarcopenia. However, few studies have examined the association between serum creatinine/serum cystatin C ratio and frailty. The objective of this study is to investigate the relationship between the serum creatinine/serum cystatin C ratio and frailty among older adults residing in the community. METHODS AND MATERIALS: A Total of 1926 community-dwelling older adults aged ≥ 60 years in the 2011 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The participants' frailty status was determined using a 39 item frailty index (FI), which classified individuals as "robust" (FI ≤ 0.1), "pre-frailty" (0.1 < FI < 0.25), or "frailty" (FI ≥ 0.25). The Scr/Cys C ratio was determined by dividing the serum creatinine level (mg/dL) by the cystatin C level (mg/L). The one-way analysis of variance(ANOVA) and Chi-squared test (χ2)were applied to compare the differences between the 3 groups. Both linear regression and logistic regression models were used to further investigate the relationship between Scr/Cys C ratio and frailty. RESULTS: After adjusting for potential confounding factors, the study revealed that participants in the Q1 quartile of Scr/Cys C ratio had increased odds of frailty (Q1vs.Q4: OR = 1.880, 95% CI 1.126-3.139, p = 0.016) compared with those in the Q4 quartile group. In fully adjusted logistic regression models, male participants in the Q2 quartile of Scr/Cys C ratio were significantly correlated with higher odds of pre-frailty (Q2 vs.Q4: OR = 1.693, 95%CI 1.040-2.758, p = 0.034). However, this correlation was not observed in females (OR = 0.984, 95% CI 0.589-1.642, p = 0.950,). Additionally, the study observed an increase in both the frailty index and the incidence of frailty as age increased in both males and females. CONCLUSION: Among community-dwelling older adults, lower Serum creatinine to cystatin C ratio were found to be associated with increased odds of frailty prevalence in males.

Clinical significance and normal reference value of serum creatinine to cystatin C ratio in children.

BACKGROUND & AIMS: Sarcopenia is a serious problem in adults and children. However, limited modalities are available for diagnosing pediatric sarcopenia. The serum creatinine to cystatin C ratio (Cre/CysC ratio) is a promising method for muscle quantification, although its clinical significance in the pediatric population is unknown. This study aimed to evaluate the relationship between the Cre/CysC ratio and physical performance. METHODS: This was a single-center retrospective study. Patients aged <15 years who had visited the University of Tokyo Hospital for measurements of serum creatinine and cystatin C levels, body height, and body weight were included. The patients were assigned according to their age (<2 or ≥2 years), and the relationship between the Cre/CysC ratio and physical performance at the time of measurement was analyzed. RESULTS: We included 266 patients, revealing a significant relationship between Cre/CysC ratio and physical performance in children aged ≥2 years (p < 0.001) but not in children aged <2 years (p = 0.42). The repeater-operator curve analysis of Cre/CysC to predict bedridden status showed good performance (the area under the curve was 0.82 (95% CI, 0.75-0.89)) and the cut-off value 0.44 had good accuracy (sensitivity 0.87, specificity 0.61). CONCLUSIONS: The Cre/CysC ratio was a significant marker of impaired physical performance, and a Cre/CysC ratio <0.44 accurately predicted bedridden status in children aged >2 years.

A Pilot Study on Circulating, Cellular, and Tissue Biomarkers in Osteosarcopenic Patients.

Aging comes with the loss of muscle and bone mass, leading to a condition known as osteosarcopenia. Circulating, cellular, and tissue biomarkers research for osteosarcopenia is relatively scarce and, currently, no established biomarkers exist. Here we find that osteosarcopenic patients exhibited elevated basophils and TNFα levels, along with decreased aPPT, PT/INR, IL15, alpha-Klotho, DHEA-S, and FGF-2 expression and distinctive bone and muscle tissue micro-architecture and biomarker expressions. They also displayed an increase in osteoclast precursors with a concomitant imbalance towards spontaneous osteoclastogenesis. Similarities were noted with osteopenic and sarcopenic patients, including a lower neutrophil percentage and altered cytokine expression. A linear discriminant analysis (LDA) on models based on selected biomarkers showed a classification accuracy in the range of 61-78%. Collectively, our data provide compelling evidence for novel biomarkers for osteosarcopenia that may hold potential as diagnostic tools to promote healthy aging.

Impact of sarcopenia and vitamin D levels on the severity of lower urinary tract symptoms in older males.

OBJECTIVES: To assess the impact of sarcopenia and vitamin D levels on the severity of lower urinary tract symptoms (LUTS). METHODS: A total of 193 male patients, aged 60 years and above, who visited the geriatric outpatient clinic at Ibn-i Sina Hospital in Ankara, Turkey, between December 2019 and March 2021, were enrolled. Sarcopenia was diagnosed according to the criteria set by the European Working Group on Sarcopenia in Older People. The presence and severity of lower urinary tract symptoms were assessed using the International Prostate Symptom Score questionnaire, categorizing symptom severity as mild or moderate-to-severe. RESULTS: The median patient age was 71 years (range: 66-77). Sarcopenia affected 24.9% of the population studied. Mild LUTS was observed in 43.5% and moderate-to-severe LUTS was observed in 56.5% of patients. Sarcopenia prevalence was significantly higher in the individuals with moderate-to-severe LUTS compared to those with mild-LUTS (p=0.021). After adjusting for Charlson comorbidity index and age, only vitamin D levels were significantly associated with increased odds of moderate-to-severe LUTS (odds ratio [OR]=0.95, 95% confidence interval [CI]: [0.92-0.98], p=0.002). Sarcopenia was not significantly associated with the severity of LUTS (OR=2.04, 95% CI: [0.94-4.45], p=0.070). An inverse linear trend was observed between quartiles of 25 (OH) vitamin D and LUTS severity. As 25 (OH)vitamin D levels increased, the proportion of patients with moderate-to-severe LUTS decreased (p=0.023). CONCLUSION: Sarcopenia did not significantly impact LUTS severity, but low vitamin D levels were associated with moderate-to-severe LUTS.

Prevalence of body composition phenotypes and their associations with glycemic, lipidic, and inflammatory biomarkers: a population-based study.

We aimed to verify the prevalence of body composition phenotypes and the association of glycemic, lipidic, and inflammatory biomarkers with such phenotypes. This is a cross-sectional, population-based study, with 720 participants aged 20 to 59 years. Body composition was assessed by dual-energy X-ray absorptiometry. Obesity was defined as body fat percentage ≥ 25% in males and ≥ 32% in females and sarcopenia by appendicular muscle mass index < 7.0kg/m2 in males and < 5.5kg/m2 in females. Sarcopenic obesity (SO) was defined as the presence of both sarcopenia and obesity. The prevalence of obesity, sarcopenia, and SO were 62.5%, 4.5%, and 6.2%, respectively. The association between biomarkers and phenotypes was verified using multinomial logistic regression models adjusted for confounding factors. The models showed that increased glycemia (OR = 3.39; 95%CI: 1.83-6.27), total cholesterol (TC) (OR = 2.24; 95%CI: 1.35-3.70), LDL-c (OR = 1.01; 95%CI: 1.00-1.02), VLDL-c (OR = 1.04; 95%CI: 1.02-1.06), non-HDL-c (OR = 1.02; 95%CI: 1.01-1.03), triglycerides (Tg) (OR = 3.66; 95%CI: 2.20-6.06), and decreased HDL-c (OR = 0.97; 95%CI: 0.95-0.98) were significantly associated with the obesity phenotype. Increased HOMA-IR (OR = 3.94; 95%CI: 1.69-9.21), LDL-c (OR = 1.01; 95%CI: 1.00-1.02), non-HDL-c (OR = 1.01; 95%CI: 1.00-1.02), and hs-CRP (OR = 2.42; 95%CI: 1.04-5.66) were independently associated with SO phenotype. Our findings indicate that increased glycemia, TC, Tg, LDL-c, VLDL-c, non-HDL-c, and decreased HDL-c may be indicators of the obesity phenotype and that increased hs-CRP, HOMA-IR, LDL-c, and non-HDL-c appear to be indicators of the SO phenotype. Those parameters may be used as additional markers for screening.

Circulating myostatin as a biomarker of muscle mass and strength in individuals with cancer or obesity.

BACKGROUND & AIMS: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO). METHODS: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO. RESULTS: In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m2vs 9.0 kg/m2, p = 0.004; ASMMI: 6.2 kg/m2vs 7.2 kg/m2, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3. CONCLUSIONS: MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.

Associations between sarcopenia and circulating branched-chain amino acids: a cross-sectional study over 100,000 participants.

BACKGROUND: Emerging evidence suggests that alterations in BCAA metabolism may contribute to the pathogenesis of sarcopenia. However, the relationship between branched-chain amino acids (BCAAs) and sarcopenia is incompletely understood, and existing literature presents conflicting results. In this study, we conducted a community-based study involving > 100,000 United Kingdom adults to comprehensively explore the association between BCAAs and sarcopenia, and assess the potential role of muscle mass in mediating the relationship between BCAAs and muscle strength. METHODS: Multivariable linear regression analysis examined the relationship between circulating BCAAs and muscle mass/strength. Logistic regression analysis assessed the impact of circulating BCAAs and quartiles of BCAAs on sarcopenia risk. Subgroup analyses explored the variations in associations across age, and gender. Mediation analysis investigated the potential mediating effect of muscle mass on the BCAA-muscle strength relationship. RESULTS: Among 108,017 participants (mean age: 56.40 ± 8.09 years; 46.23% men), positive associations were observed between total BCAA, isoleucine, leucine, valine, and muscle mass (beta, 0.56-2.53; p < 0.05) and between total BCAA, leucine, valine, and muscle strength (beta, 0.91-3.44; p < 0.05). Logistic regression analysis revealed that increased circulating valine was associated with a 47% reduced sarcopenia risk (odds ratio = 0.53; 95% confidence interval = 0.3-0.94; p = 0.029). Subgroup analyses demonstrated strong associations between circulating BCAAs and muscle mass/strength in men and individuals aged ≥ 60 years. Mediation analysis suggested that muscle mass completely mediated the relationship between total BCAA, and valine levels and muscle strength, partially mediated the relationship between leucine levels and muscle strength, obscuring the true effect of isoleucine on muscle strength. CONCLUSION: This study suggested the potential benefits of BCAAs in preserving muscle mass/strength and highlighted muscle mass might be mediator of BCAA-muscle strength association. Our findings contribute new evidence for the clinical prevention and treatment of sarcopenia and related conditions involving muscle mass/strength loss.

Effectiveness of resistance training in modulating inflammatory biomarkers among Asian patients with sarcopenia: a systematic review and meta-analysis of randomized controlled trials.

Objective: Given the high incidence of sarcopenia among Asians, it is imperative to identify appropriate intervention methods. The International Clinical Practice Guidelines for Sarcopenia, developed by the International Conference on Sarcopenia and Frailty Research (ICFSR) task force, recommends resistance training (RT) as a primary treatment for managing sarcopenia. Inflammatory biomarkers serve as indicators of sarcopenia. However, there is currently insufficient conclusive evidence regarding the effectiveness of RT in modulating inflammatory biomarker levels among Asian participants with sarcopenia. Data sources: Four databases were utilized for this study until October 9, 2023. This study focused on randomized controlled trials (RCTs) that examined the effects of RT on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-10 (IL-10) about sarcopenia. This study has been registered in the PROSPERO database (CRD42024501855). Results: The meta-analysis included six studies from Asians involving 278 participants. The results showed a significant decrease in RT for IL-6 (weighted mean difference (WMD) = -0.73, 95% confidence interval (CI) = -1.02 to -0.44; n=5). However, no significant differences were found for TNF-α (WMD = -1.00, 95% CI = -2.47 to 0.46; n=5), CRP (WMD = -0.45, 95% CI = -1.14 to 0.23; n=3), and IL-10 (WMD = 0.13, 95% CI = -3.99 to 4.25; n=2). Subgroup analysis revealed that factors including gender selection, intervention methods, frequency, period, and duration could have a particular effect on the part of inflammatory biomarkers. Conclusion: RT has been shown to reduce part of the level of inflammatory markers, specifically IL-6, in Asian sarcopenia participants. However, other inflammatory factors, such as TNF-α, CRP, and IL-10, did not show significant changes. Further research should confirm the impact of RT on these indicators and explore the potential effects of various factors on different inflammatory markers, such as diet, body composition, and medications. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=501855, identifier CRD42024501855.

Exploring the impact of interleukins on sarcopenia development: A systematic review and meta-analysis.

BACKGROUND: The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients. METHODS: Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle-Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel-Haenszel method was used for pooled estimates. RESULTS: Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1ß, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1ß (95 % CI: 0.33 [0.12, 0.54], P < 0.05), IL-6 (95 % CI: 0.91 [0.59, 1.24], P < 0.05), and IL-10 (95 % CI: 0.11 [0.07,0.15], P < 0.05) were detected. However, no significant associations were found between serum IL-4 (95 % CI: 0.36 [-0.18, 0.42], P = 0.44), IL-8 (95 % CI: -1.05 [-3.06, 0.95], P = 0.3), IL-12 (95 % CI: -3.92 [-8.32,0.48], P = 0.08) or IL-17 (95 % CI: 0.22 [-2.43, 2.88], P = 0.87) and sarcopenia. Subgroup analysis showed no significant difference in IL-6 (95 % CI: -0.03 [-0.72, 0.66], P = 0.93) and IL-10 (95 % CI: 0.1 [-0.44, 0.64], P = 0.72) among patients with European standard sarcopenia. CONCLUSIONS: Inflammation plays a role in sarcopenia, and the serum levels of IL-1ß, IL-6, and IL-10 are associated with sarcopenia. Further research is needed to clarify these associations. CLINICAL TRIALS REGISTRATION NUMBER: CRD42024506656.

Combination of sarcopenia and systemic inflammation-based markers for predicting the prognosis of patients undergoing pancreaticoduodenectomy for pancreatic cancer.

BACKGROUND: This study aimed to evaluate the effects of sarcopenia and inflammation on the prognosis of patients with pancreatic cancer after pancreaticoduodenectomy. METHODS: Eighty patients who had undergone pancreaticoduodenectomy for pancreatic cancer between July 2010 and December 2023 were included in this study. The psoas muscle index was used to assess sarcopenia. The C-reactive protein-to-albumin ratio, prognostic nutritional index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were used to calculate the preoperative inflammatory marker levels. The prognostic factors for overall survival were determined using Cox regression analysis. RESULTS: Twenty-four patients were diagnosed with sarcopenia. Sarcopenia showed a significant association with advanced tumor stage. Univariate analysis revealed a significant reduction in overall survival in patients with a prognostic nutritional index of <45, C-reactive protein-to-albumin ratio of ≥0.047, cancer antigen 19-9 levels of ≥130 U/mL, sarcopenia, lymph node metastasis, and vascular invasion. Multivariate analysis revealed that a C-reactive protein-to-albumin ratio of ≥0.047 (hazards ratio, 3.383; 95% confidence interval: 1.384-8.689; p< 0.001), cancer antigen 19-9 levels of ≥130 U/mL (hazards ratio, 2.720; 95% confidence interval: 1.291-6.060; p = 0.008), sarcopenia (hazards ratio, 3.256; 95% confidence interval: 1.535-7.072; p = 0.002) and vascular invasion (hazards ratio, 2.092; 95% confidence interval: 1.057-4.170; p = 0.034) were independent predictors of overall survival. Overall survival in the sarcopenia and high C-reactive protein-to-albumin ratio groups was significantly poorer than that in the non-sarcopenia and low C-reactive protein-to-albumin ratio and sarcopenia or high C-reactive protein-to-albumin ratio groups. CONCLUSION: Sarcopenia and a high C-reactive protein-to-albumin ratio are independent prognostic factors in patients with pancreatic cancer after pancreaticoduodenectomy. Thus, sarcopenia may have a better prognostic value when combined with the C-reactive protein-to-albumin ratio.

Causal association of circulating cytokines with sarcopenia-related traits: A Mendelian randomization study.

BACKGROUND: Observational studies have reported that circulating cytokines are associated with sarcopenia. However, the causal relationship between circulating cytokines and sarcopenia has not been elucidated. OBJECTIVES: This study aimed to investigate the causal relationship between circulating cytokines and sarcopenia with genetic data using Mendelian randomization (MR). METHODS: Two-sample bidirectional MR analysis was performed to investigate the causal relationship in individuals of European ancestry. The publicly available genome-wide association study statistics were used to select the key eligible single nucleotide polymorphisms significantly associated with circulating cytokines. Multiple MR analysis approaches, including inverse variance weighted (IVW), MR-Egger, weighted median method (WMM), and MR-Pleiotropy residual Sum and Outlier (MR-PRESSO) methods, were used for the analysis. Sarcopenia-related traits were appendicular lean mass (ALM) and grip strength. RESULTS: This study demonstrated the causal effect of genetically predicted circulating interleukin interleukin-16 (IL16) levels on both ALM [odds ratio (OR) = 0.990, 95% confidence interval (CI): 0.980-1.000, P = 0.049] and grip strength (OR = 0.971, 95% CI: 0.948-0.995, P = 0.020]. Additionally, C-X-C motif chemokine ligand 10 (CXCL10), interleukin-1beta (IL1B), and hepatocyte growth factor (HGF) were correlated with ALM, while vascular endothelial growth factor (VEGF), interleukin-12 (IL12), and interleukin-15 (IL15) were correlated with grip strength. The results of MR-Egger, weighted median, weighted mode, and simple mode methods were consistent with the IVW estimates. Sensitivity analysis revealed that horizontal pleiotropy did not bias the causal estimates. CONCLUSION: These findings indicate that inflammatory cytokines exert a significant causal effect on sarcopenia and provide promising leads for the development of novel therapeutic targets for the disease. By evaluating the role of circulating cytokines in the pathologic condition via a genetic epidemiological approach, our study made contributions to a further investigation of underlying mechanisms of sarcopenia.

Low serum manganese as a noninvasive marker predicting the presence of myosteatosis among hospitalized patients with cirrhosis.

Emerging evidence expands on a close connection between trace elements and muscular abnormalities, mostly focusing on sarcopenia. We hypothesized an association between concentrations of serum trace elements and myosteatosis, given that myosteatosis has a more pronounced clinical implication relative to sarcopenia, but there is a paucity of data in patients with cirrhosis. Consecutive patients were hospitalized for cirrhosis-associated complications. Serum trace elements (zinc, copper, manganese [Mn], magnesium, calcium, and iron) were measured by inductively coupled plasma mass spectrometry. The presence of myosteatosis was defined according to computed tomography-demarcated intramuscular adipose tissue content. In total, the 295 patients with cirrhosis analyzed had a median age of 63 years and 53.6% were male. Among them, 42 patients presented with myosteatosis (14.2%) and concomitant higher Model for End-stage Liver Disease-Sodium and triglyceride concentrations and lower neutrophil counts and serum Mn concentrations (all P < .05). No differences were found regarding other 5 trace elements in patients with versus without myosteatosis. The median serum Mn concentrations were 1.16 µg/L, and this population was categorized into high-Mn and low-Mn groups. The proportion of myosteatosis was significantly lower in high-Mn group than that in low-Mn group (8.1% vs 20.4%, P < .001). Univariable binary logistic regression indicated that low Mn was associated with myosteatosis (odds ratio, 2.906; 95% confidence interval, 1.424-5.932; P = .003) in the context of cirrhosis. This result was validated according to multivariable analysis by adjusting for confounding factors. In conclusion, low serum Mn can be predictive of myosteatosis, a novel muscular abnormality representing more clinical relevance and close relation to inferior outcomes among cirrhosis.

Associations of CBC-Derived inflammatory indicators with sarcopenia and mortality in adults: evidence from Nhanes 1999 ∼ 2006.

BACKGROUND: It has been proposed that inflammation plays a role in the development of sarcopenia. This study aimed to investigate the links of complete blood cell count (CBC) parameters and CBC-derived inflammatory indicators with sarcopenia and mortality. METHODS: Data pertaining to sarcopenia were extracted from the 1999-2006 National Health and Nutrition Examination Survey (NHANES), and mortality events were ascertained through the National Death Index up to December 31, 2019. The CBC-derived inflammatory indicators assessed in this study included the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-monocyte to lymphocyte ratio (NMLR), systemic inflammatory response index (SIRI), and systemic immune-inflammation index (SII). The prognostic significance of these CBC-derived inflammatory indicators was evaluated using the random survival forests (RSF) analysis. RESULTS: The study encompassed a cohort of 12,689 individuals, among whom 1,725 were diagnosed with sarcopenia. Among individuals with sarcopenia, 782 experienced all-cause mortality, and 195 succumbed to cardiovascular causes. Following adjustment for confounding variables, it was observed that elevated levels of NLR, dNLR, NMLR, SIRI, and SII were associated with an increased prevalence of sarcopenia. Among participants with sarcopenia, those in the highest quartile of NLR (HR = 1.336 [1.095-1.631]), dNLR (HR = 1.274 [1.046-1.550]), MLR (HR = 1.619 [1.290-2.032]), NMLR (HR = 1.390 [1.132-1.707]), and SIRI (HR = 1.501 [1.210-1.862]) exhibited an elevated risk of all-cause mortality compared to those in the lowest quartile of these inflammation-derived indicators. These associations were similarly observed in cardiovascular mortality (HR = 1.874 [1.169-3.003] for MLR, HR = 1.838 [1.175-2.878] for SIRI). The RSF analysis indicated that MLR exhibited the highest predictive power for both all-cause and cardiovascular mortality among individuals with sarcopenia. CONCLUSIONS: Our findings underscore the association between CBC-derived inflammatory indicators and mortality in adults with sarcopenia. Of note, MLR emerged as the most robust predictor of all-cause and cardiovascular mortality in this population.

Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health.

Introduction: Growth Differentiation Factor 15 (GDF15) is a mitokine expressed in response to various stresses whose circulating levels increase with age and are associated with numerous pathological conditions, including muscle wasting and sarcopenia. However, the use of circulating GDF15 (c-GDF15) as a biomarker of sarcopenia is still debated. Moreover, the role of GDF15 intracellular precursor, pro-GDF15, in human skeletal muscle (SM-GDF15) is not totally understood. In order to clarify these points, the association of both forms of GDF15 with parameters of muscle strength, body composition, metabolism and inflammation was investigated. Methods: the levels of c-GDF15 and SM-GDF15 were evaluated in plasma and muscle biopsies, respectively, of healthy subjects (HS) and patients with lower limb mobility impairment (LLMI), either young (<40 years-old) or old (>70 years-old). Other parameters included in the analysis were Isometric Quadriceps Strength (IQS), BMI, lean and fat mass percentage, Vastus lateralis thickness, as well as circulating levels of Adiponectin, Leptin, Resistin, IGF-1, Insulin, IL6, IL15 and c-PLIN2. Principal Component Analysis (PCA), Canonical Discriminant Analysis (CDA) and Receiving Operating Characteristics (ROC) analysis were performed. Results: c-GDF15 but not SM-GDF15 levels resulted associated with decreased IQS and IGF-1 levels in both HS and LLMI, while only in LLMI associated with increased levels of Resistin. Moreover, in LLMI both c-GDF15 and SM-GDF15 levels were associated with IL-6 levels, but interestingly SM-GDF15 is lower in LLMI with respect to HS. Furthermore, a discrimination of the four groups of subjects based on these parameters was possible with PCA and CDA. In particular HS, LLMI over 70 years or under 40 years of age were discriminated based on SM-GDF15, c-GDF15 and Insulin levels, respectively. Conclusion: our data support the idea that c-GDF15 level could be used as a biomarker of decreased muscle mass and strength. Moreover, it is suggested that c-GDF15 has a different diagnostic significance with respect to SM-GDF15, which is likely linked to a healthy and active state.

Associations between blood manganese levels and sarcopenia in adults: insights from the National Health and Nutrition Examination Survey.

Background: While increasing concerns arise about the health effects of environmental pollutants, the relationship between blood manganese (Mn) and sarcopenia has yet to be fully explored in the general population. Objective: This study aims to investigate the association between blood manganese (Mn) levels and sarcopenia in adults. Methods: In our study, we evaluated 8,135 individuals aged 18-59 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2018. We employed generalized additive model (GAM) to discern potential non-linear relationships and utilized the two-piecewise linear regression model to probe the association between blood Mn levels and sarcopenia. Results: After adjusting for potential confounders, we identified non-linear association between blood Mn levels and sarcopenia, with an inflection point at 13.45 µg/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.006 (0.996 to 1.048) and 1.082 (1.043 to 1.122), respectively. Subgroup analysis showed that the effect sizes of blood Mn on sarcopenia have significant differences in gender and different BMI groups. Conclusion: Our results showed that a reverse U-shaped curve between blood Mn levels and sarcopenia, with an identified the inflection point at blood Mn level of 13.45 µg/L.

The non-linear associations between blood manganese level and sarcopenia in patients undergoing maintenance hemodialysis: A multicenter cross-sectional study.

BACKGROUND AND AIMS: Manganese (Mn), a vital element in energy metabolism, is predominantly stored in skeletal muscles and plays a crucial role in muscle function and strength. Patients on maintenance hemodialysis (MHD) often experience muscle wasting due to metabolic disruption and inflammation. This study aimed to explore the relationship between blood Mn levels and sarcopenia in a patient population. METHODS: In this multicenter cross-sectional study, conducted from March 2021 to March 2022, 386 patients on MHD from three medical centers were included. Blood Mn levels were measured using inductively coupled plasma mass spectrometry, and body composition was assessed post-dialysis using bioelectrical impedance analysis. Grip strength was measured using a digital dynamometer. The patients were categorized into groups with and without sarcopenia. Using a generalized additive model to fit a smooth curve, we employed a generalized linear model to identify the optimal inflection point and explore the threshold effect after discovering a segmented relationship. Subsequently, a binary logistic regression analysis was conducted to investigate the relationship between blood manganese levels and the risk of sarcopenia, with adjustments made for potential confounding factors. RESULTS: A negative correlation was observed between blood Mn levels and sarcopenia-related parameters (Appendicular Skeletal Muscle Mass Index and grip strength) in Spearman's correlation analysis (both P < 0.05). After adjusting for confounding factors, a nonlinear association was identified. When blood Mn was ≤ 10.6 µg/L, the increase in sarcopenia was not statistically significant (P > 0.05). Conversely, when blood Mn exceeded 10.6 µg/L, each 1 µg/L increase raised the risk of sarcopenia by 0.1 times. Considering confounders, multivariate binary logistic regression confirmed an independent association between elevated blood Mn levels and sarcopenia. CONCLUSION: This study revealed an independent association between elevated blood Mn levels (> 10.6 µg/L) and sarcopenia in patients undergoing MHD. These findings emphasize the importance of understanding the Mn metabolism in the context of muscle health in this patient population. Further research is warranted to explore the underlying mechanisms and potential interventions for mitigating sarcopenia in patients with elevated blood Mn levels undergoing MHD.

The efficacy of nutritional screening indexes in predicting the incidence of osteosarcopenia and major osteoporotic fracture in the elderly.

INTRODUCTION: The effect of nutritional status on osteosarcopenia (OS) and major osteoporotic fracture (MOF) among the elderly is still unclear. So we aimed to compare the efficacy of the Mini-Nutrition Assessment-Short Form (MNA-sf), the Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT) for predicting OS and MOF among the elderly. MATERIALS AND METHODS: A total of 409 participants were enrolled in this prospective study. Blood biochemical indexes, nutritional status, and bone- and muscle-related examinations were assessed at initial visit to the outpatient. Participants were divided into 4 groups: (1) control; (2) osteopenia/osteoporosis; (3) sarcopenia; (4) osteosarcopenia, and then followed for 5 years, recording the occurrence time of MOF. RESULTS: The frequency values of osteopenia/osteoporosis, sarcopenia, and OS, at baseline, were respectively 13.4, 16.1, and 12% among the study samples. Correlation analysis showed that nutritional status scores were associated with body mass index, handgrip strength, albumin, bone mineral density, and physical functions. According to multivariate models, poor nutritional status was significantly associated with a higher risk of OS and MOF (P < 0.05). Survival analysis showed that the MOF rate in malnutrition group was significantly higher than normal nutrition group (P < 0.05). The receiver operator characteristic curve shows that the value of MNA-sf to diagnose OS and MOF is greater (P < 0.05). CONCLUSION: The poor nutritional status was associated with a higher risk of both OS and MOF. MNA-sf showed a superior diagnostic power for OS and MOF among the elderly. Early nutrition assessments and interventions may be key strategies to prevent OS and fractures.

Serum iron level is independently associated with sarcopenia: a retrospective study.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.