MetS Severity Research Articles

Exploring lipodystrophy gene expression in adipocytes: unveiling insights into the pathogenesis of insulin resistance, type 2 diabetes, and clustering diseases (metabolic syndrome) in Asian Indians.

Studying the molecular mechanisms of lipodystrophy can provide valuable insights into the pathophysiology of insulin resistance (IR), type 2 diabetes (T2D), and other clustering diseases [metabolic syndrome (MetS)] and its underlying adipocentric disease (MetS disease). A high-confidence lipodystrophy gene panel comprising 50 genes was created, and their expressions were measured in the visceral and subcutaneous (both peripheral and abdominal) adipose depots of MetS and non-MetS individuals at a tertiary care medical facility. Most lipodystrophy genes showed significant downregulation in MetS individuals compared to non-MetS individuals in both subcutaneous and visceral depots. In the abdominal compartment, all the genes showed relatively higher expression in visceral depot as compared to their subcutaneous counterpart, and this difference narrowed with increasing severity of MetS. Their expression level shows an inverse correlation with T2D, MetS, and HOMA-IR and with other T2D-related intermediate traits. Results also demonstrated that individualization of MetS patients could be done based on adipose tissue expression of just 12 genes. Adipose tissue expression of lipodystrophy genes shows an association with MetS and its intermediate phenotypic traits. Mutations of these genes are known to cause congenital lipodystrophy syndromes, whereas their altered expression in adipose tissue contributes to the pathogenesis of IR, T2D, and MetS.

Metabolic dysfunction and incidence of heart failure subtypes among Black individuals: The Jackson Heart Study.

The extent to which metabolic syndrome (MetS) severity influences subclinical myocardial remodelling, heart failure (HF) incidence and subtypes, remains unclear. We assessed the association of MetS with incident HF (including ejection fraction subtypes) among Black individuals. We included 4069 Jackson Heart Study participants (mean age 54.4 years, 63.8% women, 37.2% with MetS) without HF. We categorized participants based on MetS status and MetS severity scores (based on waist circumference [MetS-Z-WC] and body mass index [MetS-Z-BMI]). We assessed the associations of MetS indices with echocardiographic parameters, biomarkers of myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI] and B-type natriuretic peptide [BNP]) and incident HF hospitalizations including HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MetS severity was associated with subclinical cardiac remodelling (assessed by echocardiographic measures and biomarkers of myocardial damage). Over a median of 12 years, 319 participants developed HF (157 HFpEF, 149 HFrEF and 13 HF of unknown type). MetS was associated with a twofold greater risk of HF (hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.64-2.61). Compared to the lowest quartile (Q1) of MetS-Z-WC, the highest quartile (Q4) conferred a higher risk of HF (HR 2.35, 95% CI 1.67-3.30), with a stronger association for HFpEF (Q4 vs. Q1: HR 4.94, 95% CI 2.67-9.14) vs. HFrEF (HR 1.69, 95% CI 1.06-2.70). Metabolic syndrome severity was associated with both HF subtypes among Black individuals, highlighting the importance of optimal metabolic health for preventing HF.

Association of metabolic syndrome severity with frailty progression among Chinese middle and old-aged adults: a longitudinal study

BackgroundThe binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China.MethodParticipants from the 2011–2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations.ResultsA higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(β per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(β = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models.ConclusionsOur findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.

Gut microbiome and metabolism alterations in schizophrenia with metabolic syndrome severity

BackgroundSchizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown.MethodsThis study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses.ResultsA genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis.ConclusionsOur multi–omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.

Research advances in understanding crosstalk between organs and pancreatic β-cell dysfunction.

Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetesmellitus (T2DM). Previous studies have identified a link between β-cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic β-cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic β-cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of β-cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic β-cell dysfunction.

Near-infrared reactance spectroscopy-derived visceral adipose tissue for the assessment of metabolic syndrome in a multi-ethnic sample of young adults.

Visceral adipose tissue (VAT) is highly associated with metabolic syndrome (MetS), which is rapidly increasing in young adults. However, accessible VAT measurement methods are limited, restricting the use of VAT in early detection. This cross-sectional study sought to determine if near-infrared reactance spectroscopy (NIRS)-derived VAT (VATNIRS) was associated with MetS in a multi-ethnic sample of young adults. A total of 107 male and female (F:62, M:45) participants (age: 23.0 ± 4.3y; BMI: 27.1 ± 6.6 kg/m2) completed measurements of fasting blood pressure, blood glucose (FBG), blood lipids, and anthropometric assessments including waist circumference and VATNIRS. MetS severity (MetSindex) was calculated from the aforementioned risk factors using sex and race-specific equations. VATNIRS was higher in participants with, and at risk for, MetS compared to those with lower risks (all p < .001). VATNIRS was positively associated with MetSindex for all groups (all p < .001). VATNIRS showed positive associations with systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), LDL-C and LDL-C-related biomarkers, and FBG; and negative associations with HDL-C and HDL-C-to-total cholesterol ratio (all p < .050). Associations between VATNIRS and blood pressure for females, and LDL-C and LDL-C-related biomarkers for males, were nonsignificant (all p > .050). VATNIRS was positively associated with DBP in African-American participants, and SBP in White participants, resulting in positive associations with MAP for both groups (all p < .050). VATNIRS is associated with MetS and individual MetS risks factors in a multi-ethnic sample of young adults; providing a noninvasive, cost-effective, portable, and accessible method that may assist in the early detection of MetS and other cardiometabolic abnormalities.

Longitudinal associations of DXA-measured visceral adipose tissue and cardiometabolic risk in middle-to-older aged adults

Background and aimsDXA-measured visceral adipose tissue (VATDXA) is associated with adverse cardiometabolic risk profiles in cross-sectional studies, but longitudinal associations have not been investigated. We examined the longitudinal associations of baseline and change in VATDXA with future cardiometabolic risk in Australian participants of the Busselton Healthy Ageing study. Methods and resultsWe studied 3569 participants (54.7% female, aged 46–70 years) with data on VATDXA (GE Lunar Prodigy) and cardiometabolic risk factors at baseline and 6 years follow-up. The associations were examined using logistic and linear regression models, adjusting for baseline age and lifestyle factors. Mean baseline VATDXA mass was 1653 ± 880 g and 855 ± 580 g, and mean change in VATDXA +99 ± 500 g and +58 ± 312 g in males and females, respectively. Among all participants, 182 males (11.3%) and 197 females (10.1%) developed incident metabolic syndrome (MetS). Baseline VATDXA was associated with incident MetS with an adjusted odds ratio of 2.53 (95% CI: 2.03, 3.15) in males and 2.78 (2.30, 3.36) in females per SD increment. There was a graded positive association between longitudinal change in VATDXA and MetS severity z score in both sexes adjusted for baseline VAT (P < 0.001). All the above associations remained significant after further adjustment for baseline or change in BMI, waist circumference or waist-to-hip ratio in respective models (all P < 0.001). ConclusionsHigher baseline and greater longitudinal increase in VATDXA are independently associated with raised cardiometabolic risk over time, and may serve as useful markers for identifying middle-aged individuals at increased cardiometabolic risk.

The mediating effect of sleep duration on metabolic syndrome severity in adults: a structural equation modeling approach

BackgroundMetabolic syndrome (MetS) is associated to sleep duration. It is crucial to identify factors that disrupt sleep regulation. The study aimed to assess the indirect effect of risk factors related to MetS severity through sleep duration by utilizing a structural equation model (SEM).MethodsThe study involving 3,935 adults from the baseline data of the Ravansar Non-Communicable Disease (RaNCD) cohort study. MetS severity scores were the outcome variables. SEM was employed to explore the relationships, utilizing IBM SPSS and AMOS version 23.ResultsThe mean MetS severity score was higher in women compared to men (0.25 vs. 0.16, P = 0.003). In men, socioeconomic status (SES) has a positive direct effect (β = 0.048) and a negative indirect effect (β=-0.006) on MetS severity. Increased physical activity is directly (β=-0.036) and indirectly (β=-0.093) associated with reducing MetS severity. Nap duration is directly linked to an increase (β = 0.072) but has an indirect effect (β=-0.008) in decreasing MetS severity. In women, SES has a direct (β=-0.020) and indirect (β=-0.001) inverse relationship with MetS severity. Increased physical activity is directly (β=-0.048) and indirectly (β=-0.036) associated with decreasing MetS severity in women. Nap duration is directly associated with an increase in MetS severity (β=-0.018) but indirectly contributes to its reduction (β=-0.002). Sleep duration not only directly affects MetS severity but is also influenced by age, SES, physical activity, obesity and nap duration.ConclusionPhysical activity, SES, and nap duration directly and indirectly effect the MetS severity. Sleep duration was recognized as a mediating variable that supports the indirect effects.

Prevalence of metabolic syndrome and its associated factors in first-treatment drug-naïve schizophrenia patients: A large-scale cross-sectional study.

Metabolic syndrome (MetS), a condition that includes several risk factors specific for cardiovascular disease, is commonly detected among patients with schizophrenia (SCZ). This study elucidated the factors contributing to the development and severity of MetS in first-treatment drug-naïve (FTDN) patients with SCZ. The study enrolled 668 individuals with FTDN SCZ, aged 18-49 years, who had no exposure to antipsychotic medications and been hospitalized between February 2017 and June 2022 at the largest psychiatric specialty institution in central China. Patient sociodemographic and general clinical data were collected, and their psychopathology scores and illness severity were assessed using the Positive and Negative Symptom Scale (PANSS) and Clinical Global Impression Scale-Severity of Illness (CGI-SI), respectively. MetS score was calculated to determine the disease severity. The prevalence of MetS among this study population was 10.93%. Binary logistic regression analysis revealed onset age, female sex, total cholesterol, and red blood and white blood cell counts as risk factors for MetS, and deemed free tetraiodothyronine (FT4) and CGI-SI score as protective factors. Multiple linear regression analysis result confirmed older SCZ onset age as a risk factor for elevated MetS score. This study determined the prevalence of MetS in patients with FTDN SCZ and revealed the factors that influence the occurrence and severity of the disease. These findings will allow development of specific prevention and treatment strategies in clinical practice.

Coffee consumption might be associated with lower potential risk and severity of metabolic syndrome: national health and nutrition examination survey 2003-2018.

Metabolic syndrome (MetS) is a clinical syndrome characterized by multiple metabolic disorders and is a serious global health problem. The coffee effect, acting as one of the most prevalent beverages on metabolic syndrome, is debatable. We included patients from the National Health and Nutrition Examination Survey 2003-2018 and used a comprehensive evaluation called the MetS z-score to assess the severity of metabolic syndrome. The relationship between coffee, decaffeinated coffee, tea, and MetS z-scores was explored using a weighted linear regression. We also divided the participants into metabolic and non-metabolic syndrome groups according to the NCEP/ATP III criteria for the subgroup analysis. A total of 14,504 participants were included in this study. The results demonstrated that drinking more than three cups of coffee daily was significantly linked to lower MetS z-scores (p < 0.001). Daily coffee consumption was also associated with lower BMI (p = 0.02), systolic blood pressure (p < 0.001), Homeostatic Model Assessment for Insulin Resistance (p < 0.001), and triglycerides (p < 0.001), while it was positively correlated with HDL-C (p = 0.001). Participants who consumed more than three cups of coffee daily had a lower MetS z-score in the MetS (p < 0.001) and non-MetS (p = 0.04) groups. This research indicates that coffee consumption is linked to MetS severity. However, decaffeinated coffee and tea intake were unrelated to MetS severity.

THE IMPACT OF FORCED-RATE EXERCISE AND/OR PHOTOBIOMODULATION COMPARED TO USUAL CARE ON METABOLIC SYNDROME SEVERITY IN PEOPLE WITH PARKINSON’S DISEASE

INTRODUCTION/AIMS Metabolic syndrome (MetS) has been postulated to play a role in the progression of Parkinson’s disease (PD). Several lines of evidence also suggest that forced-rate exercise (FRE) is a potent therapy to alleviate motor and non-motor symptoms of PD, and perhaps MetS severity (MSS). However, long-term exercise adherence in people with PD (PWP) is poor. Alternative/adjunct therapies are therefore warranted. Photobiomodulation (PBM) is an emerging non-pharmaceutical/non-exercise therapy that may improve PD symptoms. Thus, this study aimed to determine the impact of FRE and/or PBM relative to usual care on MSS in PWP. METHODS Twenty participants diagnosed with PD (aged 40-80yrs) were randomised into one of four groups assigned to a different sequence of the study interventions or SHAM treatment across four 8-week study periods, each separated by a 4-week wash-out period: (1) Group A-B-C-D (n=5); (2) Group B-D- A-C (n=5); (3) Group C-A-B-D (n=5); (4) Group D-C-B-A (n=5). A-B-C-D represents PBM, FRE, FRE+PBM, and SHAM, respectively. Z-scores were derived from levels of MetS risk factors to determine the MSS (MetS z-score). Responders to a clinically significant change in MetS z-score was classified as those demonstrating a reduction of at least 0.48. RESULTS Our preliminary analysis included 17 participants with 30 complete pre- and post-MetS z-score data sets (FRE, n=5; FRE+PBM, n=7; PBM, n=9; SHAM, n=9). There was no statistically significant difference between groups in MSS change from pre-to-post intervention (p=0.82). However, the FRE group showed the greatest proportion of MSS responders: 60% (3/5) compared to FRE+PBM (43%, 3/7), PBM (44%, 4/9), and SHAM (33%, 3/9). CONCLUSION FRE may be the most efficacious method of clinically improving MSS. However, our study also suggests that a combined FRE+PBM or PBM alone could be used as an initial or supplementary treatment in ameliorating MSS and thus potentially PD progression.

Association between metabolic syndrome severity score and cardiovascular disease: results from a longitudinal cohort study on Chinese adults.

This study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults. 13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021.A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression. Both the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380-2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329-2.470), 1.746 (1.265-2.410), and 2.817 (2.015-3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk (P for non-linearity = 0.437). Similar results were found in various sensitivity analyses. The MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.

Complete Blood Count-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Children and Adolescents with Severe Obesity.

Background: Childhood obesity is a globally increasing pathological condition leading to long-term health issues such as cardiovascular diseases and metabolic syndrome (MetS). This study aimed to determine the clinical value of the Complete Blood Count-derived inflammation indexes Monocyte/HDL-C ratio (MHR), Lymphocyte/HDL-C ratio (LHR), Neutrophil/HDL-C ratio (NHR), and System Inflammation Response Index (SIRI) to predict the presence of metabolic syndrome and its association with cardiovascular risk markers (HOMA-IR, TG/HDL-C, and non-HDL-C) in children and adolescents with obesity. Methods: The study included a total of 552 children/adolescents with severe obesity (BMI: 36.4 [32.7-40.7] kg/m2; 219 males, 333 females; age: 14.8 [12.9-16.3] years), who were further subdivided based on the presence or absence of metabolic syndrome (MetS+ and MetS respectively). Results: The MHR, LHR, and NHR indexes (p < 0.0001), but not SIRI (p = 0.524), were significantly higher in the MetS+ compared to the MetS- subgroup, showing a positive correlation with the degree of MetS severity (p < 0.0001). Furthermore, MHR, LHR, and NHR were positively associated with cardiometabolic risk biomarkers (HOMA-IR: MHR p = 0.000, LHR p = 0.001, NHR p < 0.0001; TG/HDL-C: MHR, LHR, NHR p < 0.000; non-HDL-C: MHR, LHR p < 0.0001, NHR p = 0.000). Finally, the ROC curve analysis demonstrated that among the analyzed indexes, only MHR, LHR, and NHR had diagnostic value in distinguishing MetS patients among children and adolescents with obesity (MHR: AUC = 0.7045; LHR: AUC = 0.7205; NHR: AUC = 0.6934; p < 0.0001). Conclusions: In conclusion, the MHR, LHR, and NHR indexes, but not the SIRI index, can be considered useful tools for pediatricians to assess the risk of MetS and cardiometabolic diseases in children and adolescents with obesity and to develop multidisciplinary intervention strategies to counteract the widespread disease.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition.

The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition

The link between metabolic syndrome (MetS) and neurodegenerative as well as cerebrovascular conditions holds substantial implications for brain health in at-risk populations. This study elucidates the complex relationship between MetS and brain health by conducting a comprehensive examination of cardiometabolic risk factors, brain morphology, and cognitive function in 40,087 individuals. Multivariate, data-driven statistics identified a latent dimension linking more severe MetS to widespread brain morphological abnormalities, accounting for up to 71% of shared variance in the data. This dimension was replicable across sub-samples. In a mediation analysis, we could demonstrate that MetS-related brain morphological abnormalities mediated the link between MetS severity and cognitive performance in multiple domains. Employing imaging transcriptomics and connectomics, our results also suggest that MetS-related morphological abnormalities are linked to the regional cellular composition and macroscopic brain network organization. By leveraging extensive, multi-domain data combined with a dimensional stratification approach, our analysis provides profound insights into the association of MetS and brain health. These findings can inform effective therapeutic and risk mitigation strategies aimed at maintaining brain integrity.

Circulating Bone morphogenetic protein 9(BMP9) as a new biomarker for noninvasive stratification of nonalcoholic fatty liver disease and metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome (MetS). Bone morphogenetic protein 9 (BMP9) is an essential factor in glucose, lipid and energy metabolism. This study aims to investigate whether BMP9 can serve as a serological marker for the severity of NAFLD or MetS. Blood samples, clinical data and FibroTouch test were collected from consecutively recruited 263 individuals in Shanghai East hospital. All the participants were divided into three groups: the healthy controls, nonalcoholic fatty liver (NAFL) group and nonalcoholic steatohepatitis (NASH) at-risk group according to the results of FibroTouch test and liver function. Serum BMP9 levels were measured by enzyme-linked immunosorbent assay. Serum BMP9 levels were positively correlated with transaminase, triglyceride, fasting plasma glucose, glycated hemoglobin (HbA1c) and uric acid while it showed a downward trend as the increasing number of MetS components. Furthermore, it differentiated NASH at-risk (58.13 ± 2.82ng/L) from the other groups: healthy control (70.32 ± 3.70ng/L) and NAFL (64.34 ± 4.76ng/L) (p < 0.0001). Controlled attenuation parameter of liver fat and liver stiffness measurement were negatively correlated with BMP9 levels, while high-density lipoprotein levels were positively correlated. The risk of developing NAFLD increased along with elevated serum BMP9 and BMI, and a significantly higher risk was observed in men compared to women. BMP9 should be considered a protective factor for the onset and development of NAFLD, as well as a promising biomarker for the severity of the NAFLD and MetS.

The impact of metabolic syndrome severity on racial and ethnic disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Previous studies have examined the effects of metabolic syndrome (MetS) rather than its severity on race and ethnic disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We used the MetS severity score, a validated sex-race-ethnicity-specific severity measure, to examine the effects of race/ethnicity on the association between MetS severity and MASLD. This study included 10,605 adult participants from the Third National Health and Nutrition Examination Survey. The MASLD diagnosis was based on ultrasound findings in patients without excessive alcohol intake or other liver diseases. MetS severity Z-scores were calculated and stratified into four categories low (1st-50th), moderate (>50th-75th), high (>75th-90th), and very high (>90th+)]. Multivariable adjusted logistic regression models with complex survey methods were used to test the effect of MetS severity on MASLD. The age-adjusted MASLD prevalence was 17.4%, 25.7%, 42.5, and 54.9% in adults with mild, moderate, high, and very high MetS severities, respectively (P-trend <0.001). MetS severity was significantly higher in patients with MASLD than in those without [mean percentile 60th vs. 44th, P<0.001]. Among patients with MASLD, Mexican-American and Black non-Hispanic females had significantly higher age-adjusted MetS severity (68th and 61st, respectively) than White non-Hispanic females 54th, while Black non-Hispanic males had significantly lower MetS severity (56th) than White non-Hispanic males (70th) (P-Interaction = 0.02). Adults with high and very high MetS severity had 2.27 (95% CI:1.70 to 3.03) and 3.12 (95% CI:2.20 to 4.42), respectively, higher adjusted odds of MASLD than those with mild MetS severity. Racial/ethnic disparities in MetS severity play a pivotal role in the risk of MASLD. Our findings highlight the potential clinical utility of the MetS severity score in identifying at-risk individuals, which will help guide targeted prevention and tailoring management strategies to mitigate the MASLD burden.

Galectin-3, Metabolic Risk, and Incident Heart Failure: The ARIC Study.

It is unclear how metabolic syndrome (MetS) and diabetes affect Gal-3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal-3, and their joint associations with incident HF. We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996-1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross-sectional associations of metabolic risk categories with high Gal-3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal-3 quartiles with HF. In cross-sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10-1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32-1.92]) were associated with elevated Gal-3. Over a median follow-up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal-3 in the lowest quartile, the combination of MetS with diabetes and Gal-3 ≥75th percentile was associated with a 4-fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30-5.73]). Gal-3 provided HF prognostic information above and beyond MetS, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, and CRP (C-reactive protein) (ΔC statistic for models with versus without Gal-3: 0.003; P=0.004). MetS and diabetes are associated with elevated Gal-3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal-3.

Complete Blood Count (CBC)-Derived Inflammation Indexes Are Useful in Predicting Metabolic Syndrome in Adults with Severe Obesity.

Background: Metabolic syndrome (MetS) is a globally increasing pathological condition. Recent research highlighted the utility of complete blood count-derived (CBC) inflammation indexes to predict MetS in adults with obesity. Methods: This study examined CBC-derived inflammation indexes (NHR, LHR, MHR, PHR, SIRI, AISI, and SII) in 231 adults with severe obesity (88 males, 143 females; age: 52.3 [36.4-63.3] years), divided based on the presence (MetS+) or absence (MetS-) of MetS. The relationships between the indexes and the cardiometabolic risk biomarkers HOMA-IR, TG/HDL-C, and non-HDL-C were also evaluated. Results: Individuals with metabolic syndrome (MetS+) had significantly higher values of MHR, LHR, NHR, PHR, and SIRI than those without (MetS-) (MHR and NHR: p < 0.0001; LHR: p = 0.001; PHR: p = 0.011; SIRI: p = 0.021). These values were positively correlated with the degree of MetS severity. Logistic regression (MHR and NHR: p = 0.000; LHR: p = 0.002; PHR: p = 0.022; SIRI: p = 0.040) and ROC analysis (MHR: AUC = 0.6604; LHR: AUC = 0.6343; NHR: AUC = 0.6741; PHR: AUC = 0.6054; SIRI: AUC = 0.5955) confirmed the predictive potential of CBC-derived inflammation indexes for MetS in individuals with severe obesity. CBC-derived inflammation indexes also correlated with HOMA-IR (MHR, LHR, and NHR: p < 0.0001; PHR: p < 0.001; SIRI: p = 0.000) and TG/HDL-C (MHR, LHR, NHR and PHR: p < 0.0001; SIRI: p = 0.006). Conclusions: In conclusion, this study validates CBC-derived inflammation indexes for predicting MetS in individuals with severe obesity. The relationships between these indexes and cardiometabolic risk factors can enable clinicians to better grade MetS associated with obesity.

Elevated serum levels of leukocyte cell-derived chemotaxin 2 are associated with the prevalence of metabolic syndrome.

Inflammation is central to the pathogenesis of metabolic syndrome (MetS). Leukocyte cell-derived chemotaxin 2 (LECT2) is constitutively secreted in response to inflammatory stimuli and oxidative stress contributing to tissue or systemic inflammation. We explored the relationship between LECT2 levels and MetS severity in humans and mice. Serum LECT2 levels were measured in 210 participants with MetS and 114 without MetS (non-MetS). LECT2 expression in the liver and adipose tissue was also examined in mice fed a high-fat diet (HFD) and genetically obese (ob/ob) mice. Serum LECT2 levels were significantly higher in MetS participants than in non-MetS participants (7.47[3.36-17.14] vs. 3.74[2.61-5.82], P < 0.001). Particularly, serum LECT2 levels were significantly elevated in participants with hypertension, central obesity, diabetes mellitus (DM), hyperglycaemia, elevated triglyceride (TG) levels, and reduced high-density lipoprotein cholesterol (HDL-C) levels compared to those in participants without these conditions. Pearson's correlation analysisshowed that serum LECT2 levels were positively associated with conventional risk factors in all patients. Moreover, LECT2 was positively associated with the number of MetS components (r = 0.355, P < 0.001), indicating that higher serum LECT2 levels reflected MetS severity. Multivariate regression analysis revealed that a one standard deviation increase in LECT2 was associated with an odds ratio of 1.52 (1.01-2.29, P = 0.044) for MetS prevalence after adjusting for age, sex, body mass index, waist circumference, smoking status, white blood cell count, fasting blood glucose, TG, total cholesterol, HDL-C, blood urea nitrogen, and alanine aminotransferase. Receiver operating characteristic curve analysis confirmed the strong predictive ability of serum LECT2 levels for MetS. The optimum serum LECT2 cut-off value was 9.05. The area under the curve was 0.73 (95% confidence interval 0.68-0.78, P < 0.001), with a sensitivity and specificity of 45.71% and 95.61%, respectively. Additionally, LECT2 expression levels were higher at baseline and dramatically enhanced in metabolic organs (e.g. the liver) and adipose tissue in HFD-induced obese mice and ob/ob mice. Increased LECT2 levels were significantly and independently associated with the presence and severity of MetS, indicating that LECT2 could be used as a novel biomarker and clinical predictor of MetS.