Clustering Of Cardiometabolic Risk Factors Research Articles

Severe Obesity Defined by Percentiles of WHO and Cardiometabolic Risk in Youth with Obesity

Background/Objectives: The pediatric definition of severe obesity (OB) depends on the body mass index (BMI) references. We evaluated different BMI-derived metrics of the World Health Organization (WHO) system to define which cut-off is associated with the highest cardiometabolic risk (CMR); Methods: In this multicentric study, data were retrieved for 3727 youths (1937 boys; 2225 children, 1502 adolescents). OB was defined as BMI > 97th percentile (BMI97th), severe OB was defined as BMI > 99th percentile (BMI99th), BMI ≥ 120% of the 97th percentile (120% BMI97th), or BMI Z-score > 3 (WHO tables), or BMI ≥ the International Obesity Task Force (IOTF) value crossing a BMI of 35 kg/m2 at the age of 18 (IOTF35). The continuous CMR Z-score (sum of residual standardized for age and sex of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, and HDL-cholesterol x −1) and the cluster of at least two CMR factors (hypertension, high triglycerides, low HDL-cholesterol, and high waist-to-height ratio) were calculated. Results: Continuous CMR Z-score was significantly higher both in children or adolescents with severe OB defined by 120% BMI97th compared to BMI99th (p < 0.0001), while it was lower only in adolescents with severe OB defined by 120% BMI97th compared to BMI Z-score >3 (p < 0.0001). Compared to 120% BMI97th, BMI Z-score > 3 and IOTF35 had higher specificity, but lower sensitivity in identifying children and adolescents with clustered CMR factors. Conclusions: The definition of severe OB based on 120% BMI97th is superior to BMI99th but it is inferior to BMI Z score > 3 as far as the association between severe OB and CMR factors is concerned. Pediatricians should take into consideration the implication of the use of different BMI metrics in those countries that recommend the WHO system. WHO BMI Z-score > 3 and IOTF35 can be used interchangeably to predict cardiometabolic risk.

Effects of Whole-Body Electromyostimulation on Metabolic Syndrome in Adults at Moderate-to-High Cardiometabolic Risk—A Systematic Review and Meta-Analysis

In the present work, we aimed to determine the effect of whole-body electromyostimulation (WB-EMS) on metabolic syndrome (MetS) as a cluster of cardiometabolic risk factors in people at moderate-to-high cardiometabolic risk. The present meta-analysis is based on a systematic literature search of a recent evidence map, which searched five electronic databases, two registers, and Google Scholar, according to PRISMA, until 31 March 2023. Controlled trials comprising adult cohorts with central obesity that compared the effect of WB-EMS versus controls using a continuous score representing MetS were included. We applied a random-effects meta-analysis and used the inverse heterogeneity model to analyze the data of the five eligible trials identified by our search. Outcome measures were standardized mean differences (SMDs) with 95% confidence intervals (95%-CIs). The risk of bias was determined using the PEDro-Score. In summary, we identified five eligible articles containing 117 participants in the WB-EMS group and 117 participants in the control group. We observed a small effect (SMD: −0.30; 95%-CI: −0.04 to −0.56) in favor of the WB-EMS intervention. The heterogeneity between the trials was very low (I2: 0%); further evidence for risks of small study/publication bias was minimal. The methodologic quality of these studies can be classified as moderate to high. In summary, the present work provides evidence of the favorable effect of WB-EMS on cardiometabolic risk in adults at moderate–high cardiometabolic risk. Considering the time effectiveness of WB-EMS, along with its safety and attractiveness, as indicated by the five studies, WB-EMS can be regarded as a feasible training option for people at cardiometabolic risk.

Grip Strength, Anthropometric Indices, and Their Combination in Screening for Metabolic Syndrome in the Korean Population

Background: Metabolic syndrome (MS) is a cluster of cardiometabolic risk factors for future diabetes and cardiovascular diseases, and low grip strength (GS) is associated with an increased risk of MS. However, the index (among absolute GS, relative GS, and anthropometric indices) that is more strongly associated with MS has not been conclusively identified. Therefore, the objective of the present study was to simultaneously examine the associations of MS with relative and absolute GS and anthropometric indices in a Korean population. Methods: In this large-scale cross-sectional study, we used data from the Korean National Health and Nutrition Examination Survey (KNHANES). A total of 20,915 subjects were included in the statistical analyses. Complex sample binary logistic regression models were used to analyze the associations between MS and indices such as the waist-to-height ratio (WHtR), body mass index (BMI), and absolute and relative GS. Results: The prevalence of MS was 40.48% in men and 34.4% in women. The mean GS values in the healthy group and MS group were 38.06 ± 0.13 and 38.06 ± 0.15 years for men (p = 0.980) and 22.72 ± 0.07 and 21.19 ± 0.11 years for women (p < 0.001), respectively. Among all the indices, the WHtR was the index most strongly associated with MS in men. Among the GS indices, the GS/weight index was closely associated with MS, and the magnitude of this association was stronger than that of the absolute GS index. In women, the WHtR was the most related index to MS among all the indices. Among the GS indices, the GS/weight and GS/BMI indices were strongly associated with MS, and the magnitudes of these associations were much greater than those of the absolute GS index. Conclusions: Although absolute and relative GS indices are strongly associated with MS in the Korean population, the strongest association was observed for the simple anthropometric index (WHtR).

Prevalence of Cardiometabolic Risk Factors in Women: Insights From the Houston HeartReach Study.

Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening. Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 test. Most participants had hypertension, overweight or obesity, and dyslipidemia. Older women (≥65 years) had the highest prevalence of all cardiometabolic risk factors. Black participants had a higher prevalence of hypertension (P = .006) and a lower prevalence of dyslipidemia (P = .009) than non-Black participants. Hispanic participants had a lower prevalence of hypertension (P < .001) and a higher prevalence of overweight or obesity (P = .03) than non-Hispanic participants. Participants in the lowest household income bracket (<$25,000) were more likely to have diabetes (P = .001) and overweight or obesity (P = .004) than participants in the highest income bracket (≥$50,000). Unemployed participants had a higher prevalence of diabetes (P < .001), overweight or obesity (P = .004), and dyslipidemia (P < .001) than employed participants. Comorbidity analysis revealed clustering of multiple cardiometabolic risk factors. Moreover, risk factor hot spots were identified by zip code, which could help select future sites for targeted screening. The analysis found that cardiometabolic risk factor prevalence varies with demographic and socioeconomic status. Geographic areas where cardiometabolic risk factor prevalence was highest were also identified. Further participant recruitment and analysis are required to create predictive models of cardiovascular disease risk in women.

Sex-specific associations between total and regional Fat-to-muscle Mass ratio and cardiometabolic risk: findings from the China National Health Survey

BackgroundThe fat-to-muscle mass ratio (FMR), integrating the antagonistic effects of fat and muscle mass, has been suggested as a valuable indicator to assess cardiometabolic health independent of overall adiposity. However, the specific associations of total and regional FMR with cardiometabolic risk are poorly understood. We aimed to examine sex-specific associations of total and regional FMR with single and clustered cardiometabolic risk factors (CRFs).Methods13,505 participants aged 20 years and above were included in the cross-sectional study. Fat mass and muscle mass were assessed using a bioelectrical impedance analysis device. FMR was estimated as fat mass divided by muscle mass in corresponding body parts (whole body, arm, leg, and trunk). Clustered CRFs was defined as the presence of two or more risk factors, including hypertension, elevated blood glucose, dyslipidemia, insulin resistance (IR), and hyperuricemia. IR was assessed by the triglyceride glucose (TyG) index. Multivariable logistic regression models were applied to explore the associations of FMR in the whole body and body parts with single and clustered CRFs.ResultsThe odds ratios (ORs) increased significantly for all single and clustered CRFs with the per quartile increase of total and regional FMR in both sexes (P for trend < 0.001), following adjustment for confounders. Among the regional parts, FMRs of the legs presented the strongest associations for clustered CRFs in both men and women, with adjusted OR of 8.54 (95% confidence interval (CI): 7.12–10.24) and 4.92 (95% CI: 4.24–5.71), respectively. Significant interactions (P for interaction < 0.05) were identified between age and FMRs across different body parts, as well as between BMI status and FMRs in different regions for clustered CRFs. Restricted cubic splines revealed significant non-linear relationships between FMRs of different body parts and clustered CRFs in both sexes (P for nonlinear < 0.05).ConclusionsFMRs in the whole body and different regions were significantly associated with single and clustered CRFs in the general Chinese population. The association between FMR and clustered CRFs was more pronounced in youngers than in the elderly.

Childhood cardiometabolic risk factors associated with the perinatal environment of the maternal-paternal-child triad.

Clustering of cardiometabolic risk factors in childhood significantly increases the risk of atherosclerotic cardiovascular disease later in life. Identification of modifiable parental factors that contribute to offspring cardiometabolic health is critical for the prevention of disease. The objective was to identify factors associated with child cardiometabolic risk factors at age 5 years. Triads from a longitudinal cohort were recalled at 5 years (n = 68). Dietary intake, anthropometrics, physical activity and serum-based risk factors were collected. Best subset selection, linear and logistic regressions were used to identify triad variables associated with increased risk of cardiometabolic risk factor clustering at age 5 years. In this cohort, best subset modelling revealed that increased paternal fat mass, serum low-density lipoproteins and triglycerides, maternal dietary added sugar and being female were associated with increased odds of offspring having two or more cardiometabolic risk factors at age 5 years. Dietary and exercise interventions prior to conception targeting paternal adiposity and dyslipidaemia as well as maternal dietary habits could decrease children's cardiometabolic risk in later life.

Predictive value of neck circumference for cardiometabolic risk in children

Objective: To investigate the predictive value of neck circumference on cardiometabolic risk in children. Methods: This was a cross-sectional study of natural sources. As the prediction cohort, clinical data were collected from 3 443 children aged 5-14 years who underwent physical examination in the Department of Child Healthcare, Children's Hospital of Nanjing Medical University from July 2021 to September 2022. As the validation cohort for external validation, clinical data were collected from 604 children aged 5-14 years who underwent physical examination in the Department of Child Healthcare, Children's Hospital of Nanjing Medical University from October 2022 to March 2023. Height, weight, neck circumference, waist circumference and body composition were measured in both groups, and body mass index, neck circumference to height ratio (NHtR), waist circumference to height ratio, body fat percentage and skeletal muscle percentage were calculated. Systolic blood pressure, diastolic blood pressure, fasting blood glucose, blood lipid and uric acid and other cardiovascular and metabolic risk indicators were collected in both groups. The prediction cohort was further stratified into clustered and non-clustered groups based on the clustering of cardiometabolic risk factors (CCRF). Various variables between these 2 groups were compared using the Mann-Whitney U test. Pearson correlation and binary Logistic regression were conducted to investigate the correlations between neck circumference and cardiovascular metabolic risk factors. The accuracy of NHtR in predicting the CCRF was evaluated using the area under the curve (AUC) of receiver operating characteristic (ROC). The cutoff value was determined using the Youden index. The validation cohort was then divided into groups above and below the cutoff value, and the detection rate of CCRF between the 2 groups was compared using the χ2 test for validation. Results: In the prediction cohort of 3 443 children (2 316 boys and 1 127 girls), 1 395 (40.5%) children were overweight or obese, and 1 157 (33.6%) children had CCRF. Pearson correlation analysis revealed all significant positive correlations (all P<0.01) between neck circumference and systolic blood pressure (r=0.47, 0.39), diastolic blood pressure (r=0.27, 0.21), uric acid (r=0.36, 0.30), and triglycerides (r=0.20, 0.20) after adjusting for age in both males and females. Among both males and females, neck circumference both showed significant negative correlation (both P<0.01) with high-density lipoprotein cholesterol (r=-0.27, -0.28), and no correlation with fasting glucose levels (r=0.03, -0.03, both P>0.05). After adjusting for gender, age, and body fat percentage, increased body mass index, neck circumference, or waist circumference increased the risks of hypertension (OR=1.23, 1.39, 1.07, all P<0.001), hyperuricemia (OR=1.16, 1.23, 1.05, all P<0.001), hypertriglyceridemia (OR=1.08, 1.16, 1.02, all P<0.01), low high-density lipoprotein cholesterol (OR=1.10, 1.27, 1.03, all P<0.01), and the CCRF (OR=1.51, 1.73, 1.15, all P<0.01). The areas under the ROC curves of NHtR in predicting CCRF was 0.73, with sensitivity and specificity at 0.66 and 0.71, respectively. The corresponding optimal cut-off value was 0.21. Validation with 604 children confirmed that the detection of CCRF in the NHtR≥0.21 group was 3.29 times (60.5% (112/185) vs. 18.7% (79/422),χ2=107.82, P<0.01) higher compared to the NHtR <0.21 group. Conclusions: Neck circumference is associated with cardiovascular metabolic risks such as hypertension, hyperlipidemia, hyperglycemia, and hyperuricemia in children. When the NHtR is ≥0.21, there is an increased likelihood of CCRF.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries

AimsThe clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). MethodsWe analyzed data from 34,224 youths (51.0 % boys, aged 6–18 years) with CMRFs, 5004 (49.5 % boys, aged 6–18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6–17 years) with PWV measurement from 20 pediatric samples across 14 countries. ResultsWHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75–0.78) to 0.78 (0.76–0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74–0.79) to 0.77 (0.74–0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64–0.71) to 0.70 (0.66–0.73) for high cIMT (≥P95 values) and from 0.60 (0.58–0.66) to 0.62 (0.58–0.66) for high PWV (≥P95 values). ConclusionsOur findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

15 Discrepancies in Medication Usage and Lifestyle Modification Referrals in Metabolic Syndrome is Dependent on how the Syndrome is Coded: A TriNetX Study

OBJECTIVES/GOALS: ICD-10 coding inconsistencies hinder timely recognition and treatment of metabolic syndrome (MetS), posing a significant risk for cardiometabolic disease progression. This study employed a digital phenotype for MetS and compared odds for medication and lifestyle intervention compared to those coded for MetS. METHODS/STUDY POPULATION: MetS is a cluster of cardiometabolic risk factors that increase risk for numerous adverse clinical outcomes. Patients with MetS were identified through electronic medical records on TriNetX LLC using the standard ICD-10 code or through a digital phenotype, involving grouping codes for the individual components. Percentage of patients with MetS not captured with the standard code was identified. In addition, disparities in blood pressure, glucose, lipid-lowering medication, and lifestyle intervention between the coding schemas were assessed, shedding light on healthcare inequities and informing targeted interventions. Odds ratios (RR) were presented for all outcomes. RESULTS/ANTICIPATED RESULTS: Patient demographics and lab values were similar between the standard code and digital phenotype cohorts. Of the 4.3 million individuals aged 50 to 80 identified as having MetS using the digital phenotype in the TriNetX research network, only 1.78% of participants shared the standard code. Individuals with the digital phenotype for MetS were at lower odds in receiving glucose lowering medication (OR: 2.11, 95% CI: 1.98–2.13, p &lt;0.001) and exercise or nutrition-based intervention advice (OR: 1.76, 95% CI: 1.55–1.96, p &lt;0.001) after controlling for demographics and lab values for each MetS component. DISCUSSION/SIGNIFICANCE: This project utilized TriNetX to create a digital phenotype for MetS, and suggests most patients are not coded for it using the standard ICD-10 system. This is troublesome given those with the standard code are less likely to receive certain interventions.

57 Utilizing a Digital Phenotype for Metabolic Syndrome to Elucidate Risk Profiles for Neurocognitive Disease: An Electronic Medical Record Study

OBJECTIVES/GOALS: Metabolic syndrome (MetS), defined as a cluster of cardiometabolic disease risk factors, is seldom coded using the ICD-10 system in electronic medical records (EMR). The goal of this study was to use EMR to construct MetS with a digital phenotype to amplify the pool of patients available to assess risk for neurocognitive disease in this population. METHODS/STUDY POPULATION: A digital phenotype using the EMR platform TriNetX (n=38 million patients between age 50 and 80) was created by clustering codes for the individual components of MetS (insulin resistance, hypertension, dyslipidemia, and central adiposity). The research network database on TriNetX was utilized to elucidate risk ratios for neurocognitive decline, Alzheimer’s disease and related dementias (ADRDs), and cerebrovascular disease between a preclinical sample of older adults with and without MetS. Propensity score matching was used to match cohorts on demographic variables, medication use, and relevant comorbidities. Risk ratios (RR) and confidence intervals (95% CI) were presented for all outcomes. RESULTS/ANTICIPATED RESULTS: The digital phenotype for MetS expanded the sample from 29,830 to 274,703, a 10-fold increase. Sensitivity to the standard MetS ICD-10 code was 95.1%, showing strong agreement between coding schema. Older adults with MetS had higher risk of cognitive decline (RR: 1.30, 95% CI: 1.15–1.48, p &lt;0.001), ADRDs (RR: 1.48, 95% CI: 1.25–1.75, p &lt;0.001), and cerebrovascular issues (RR: 1.62, 95% CI: 1.55–1.70, p &lt;0.001) when controlling for demographics, medication, and comorbidities. MetS individuals with cerebrovascular dysfunction had even greater risks for neurocognitive decline (RR: 1.70, 95% CI: 1.38–2.08, p &lt; 0.001) and ADRDs (RR: 2.09, 95% CI: 1.56–2.80, p &lt; 0.001) than those with only MetS. DISCUSSION/SIGNIFICANCE: Implementing a digital MetS phenotype in EMR effectively increased sample size and power for analyses. Older adults with MetS have higher risk for neurocognitive decline, especially among those with cerebrovascular dysfunction, highlighting a critical intervention window prior to overt cardiometabolic disease.

Predictive Ability of Hypertriglyceridemic Waist, Hypertriglyceridemic Waist-to-Height Ratio, and Waist-to-Hip Ratio for Cardiometabolic Risk Factors Clustering Screening among Chinese Children and Adolescents*

ObjectiveHypertriglyceridemic waist (HW), hypertriglyceridemic waist-to-height ratio (HWHtR), and waist-to-hip ratio (WHR) have been shown to be indicators of cardiometabolic risk factors. However, it is not clear which indicator is more suitable for children and adolescents. We aimed to investigate the relationship between HW, HWHtR, WHR, and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. MethodsThis was a national cross-sectional study. Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6–18 years from seven provinces in China. Demographics, physical activity, dietary intake, and family history of chronic diseases were obtained through questionnaires. ANOVA, χ2 and logistic regression analysis was conducted. ResultsA significant sex difference was observed for HWHtR and WHR, but not for HW phenotype. The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents (HW: OR = 12.22, 95% CI: 9.54-15.67; HWHtR: OR = 9.70, 95% CI: 6.93-13.58). Compared with the HW and HWHtR phenotypes, the association between risk of cardiometabolic health risk factors (CHRF) clustering and high WHR was much weaker and not significant (WHR: OR = 1.14, 95% CI: 0.97-1.34). ConclusionCompared with HWHtR and WHR, the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Association between human papillomaviruses, metabolic syndrome, and all-cause death; analysis of the U.S. NHANES 2003-2004 to 2015-2016.

Human papillomavirus (HPV) is the most common sexually transmitted infection, attributed to 4.5% of all cancers worldwide. Co-infection with the metabolic syndrome (MetS), a common cluster of cardiometabolic risk factors, has been shown to increase the persistence of HPV. The purpose of this study was to estimate the association between HPV and MetS on mortality risk. Data for the current study was drawn from seven consecutive cycles (2003-2004 to 2015-2016) of the U.S. NHANES. The final analytic sample consisted of 5,101 individuals aged 18-65y with HPV and MetS information with follow-up to Dec. 31st, 2019. Baseline HPV status was assessed by either vaginal swab, penile swab or oral rinse and used to classify participants as: no HPV (n = 1,619), low (n = 1,138), probable (n = 672), and high-risk (n = 1,672; 22% type 16, and 10% type 18) HPV using IARC criteria. MetS was assessed by the Harmonized criteria. The average follow-up was 9.4 y with 240 all-cause deaths (no HPV: n = 46 deaths; low-risk: n = 60 deaths; probable: n = 37 deaths, and; high-risk: n = 97 deaths). HPV status alone revealed no associations with mortality in fully adjusted models. Cross-classification into discrete MetS/HPV strata yielded an increased risk of mortality in females with high-risk HPV/MetS relative to the no MetS/no HPV group. In this study, low, probable, and high-risk HPV and MetS were differentially related to mortality risk in men and women. Further work is necessary to separate the temporal, age, vaccination, and sex effects of HPV diagnosis in these relationships using prospective studies with detailed histories of HPV infection and persistence.

Associations of overweight and obesity with cardiometabolic risk factor clusters among Korean adolescents

This study investigated the association between overweight, obesity, and cardiometabolic risk factor clusters in Korean adolescents. We included 2182 participants (1161 boys and 1021 girls) aged 12–18 years from the Korea National Health and Nutrition Examination Survey (2016–2021). Cardiometabolic risk factors include hypertension, high low-density lipoprotein cholesterol (LDL-C) level, low high-density lipoprotein cholesterol (HDL-C) level, hypertriglyceridemia, high fasting plasma glucose level, elevated alanine aminotransferase level, and hyperuricemia. The average age was 15.1 ± 0.1 years in both boys and girls. The proportion of subjects with ≥ 1, ≥ 2, and ≥ 3 cardiometabolic risk factors was 76.5%, 49.8%, and 22.7% in obese adolescents, and 60.5%, 24.0%, and 9.1%, in overweight adolescents, respectively. Compared to adolescents with underweight/normal weight, the odds ratios (ORs) and 95% confidence intervals for the clustering of cardiometabolic risk factors were at 2.76 (1.74–4.38) for ≥ 1; 3.75 (2.11–6.66) for ≥ 2; and 4.75 (1.70–13.25) for ≥ 3 factors in obese adolescents and 1.88 (1.26–2.81) for ≥ 1 factor in overweight adolescents. Overweight and obese adolescents exhibited high cardiometabolic risk clustering. Prevention and management of overweight/obesity in Korean adolescents are emerging to mitigate health risk associated with this condition.

Novel biomarkers in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is an alarming gynaecological endocrine disorder affects women of reproductive age. Hyperandrogenism contributes for a cluster of cardio-metabolic risk factors characterized by reproductive dysfunction, polycystic ovaries, anovulation, and cosmetic dysfunctions. Although during the past decades, substantial research efforts tried to uncover the exact aetiology and pathogenesis of PCOS but owing to the complex etiology, the patho-physiological mechanisms of PCOS remains in doubt. To develop potential and highly efficient therapeutic strategies, there are many proteins which can act as potential biomarkers for PCOS. These biomarker proteins and enzymes may involve in the early detection and handling of this condition and mitigate the risk of long-term problems.

Association of serum uric acid Levels with metabolic syndromes in Korean adolescents.

The study findings investigated uric acid reference values and their association with a cluster of cardiometabolic risk factors among adolescents using the Korea National Health and Nutrition Examination Survey (KNHANES). A retrospective cross-sectional study was conducted using the KNHANES database from 2016 to 2018, involving a total of 2,462 participants aged between 10 and 18 years. Based on age- and sex-specific percentile curves for serum uric acid (SUA) levels from the KNHANES, we examined the correlation between cardiometabolic risk factors and serum uric acid levels. The percentile values of SUA varied with sex and age. In male subjects, SUA levels tended to increase from 10 to 14 years of age and plateaued after 14 years of age. Moreover, the overall uric acid level in females was found to be lower than that in males; the levels tended to increase at approximately 10 to 12 years old but were relatively consistent according to age. Mean uric acid levels increased according to obesity status in both males and females. However, correlation analysis revealed that SUA levels were associated with several metabolic risks even after adjusting for obesity. The detailed metabolic syndrome (MetS) components that were observed to be associated with an increase in uric acid levels were different between males and females, but overall, high uric acid levels increased MetS risk. Additionally, a significant increase in MetS-related odds ratio (OR) for components, including waist circumference (WC), triglyceride (TG) levels, and low high-density lipoprotein cholesterol (HDL-c), was observed. However, differences between sexes were apparent, with a more pronounced increase in OR based on SUA levels in girls. SUA levels were closely associated with MetS and its components, even in nonobese subjects. Therefore, high SUA levels in children and young adolescents should be closely monitored to prevent MetS.

Unraveling phenotypic variance in metabolic syndrome through multi-omics.

Complex multi-omics effects drive the clustering of cardiometabolic risk factors, underscoring the imperative to comprehend how individual and combined omics shape phenotypic variation. Our study partitions phenotypic variance in metabolic syndrome (MetS), blood glucose (GLU), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and blood pressure through genome, transcriptome, metabolome, and exposome (i.e., lifestyle exposome) analyses. Our analysis included a cohort of 62,822 unrelated individuals with white British ancestry, sourced from the UK biobank. We employed linear mixed models to partition phenotypic variance using the restricted maximum likelihood (REML) method, implemented in MTG2 (v2.22). We initiated the analysis by individually modeling omics, followed by subsequent integration of pairwise omics in a joint model that also accounted for the covariance and interaction between omics layers. Finally, we estimated the correlations of various omics effects between the phenotypes using bivariate REML. Significant proportions of the MetS variance were attributed to distinct data sources: genome (9.47%), transcriptome (4.24%), metabolome (14.34%), and exposome (3.77%). The phenotypic variances explained by the genome, transcriptome, metabolome, and exposome ranged from 3.28% for GLU to 25.35% for HDL-C, 0% for GLU to 19.34% for HDL-C, 4.29% for systolic blood pressure (SBP) to 35.75% for TG, and 0.89% for GLU to 10.17% for HDL-C, respectively. Significant correlations were found between genomic and transcriptomic effects for TG and HDL-C. Furthermore, significant interaction effects between omics data were detected for both MetS and its components. Interestingly, significant correlation of omics effect between the phenotypes was found. This study underscores omics' roles, interaction effects, and random-effects covariance in unveiling phenotypic variation in multi-omics domains.

Metabolic Syndrome: An Overview on Its Genetic Associations and Gene-Diet Interactions.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias and whose inter-related occurrence may increase the odds of developing type 2 diabetes and cardiovascular diseases. MetS has become one of the most studied conditions, nevertheless, due to its complex etiology, this has not been fully elucidated. Recent evidence describes that both genetic and environmental factors play an important role on its development. With the advent of genomic-wide association studies, single nucleotide polymorphisms (SNPs) have gained special importance. In this review, we present an update of the genetics surrounding MetS as a single entity as well as its corresponding risk factors, considering SNPs and gene-diet interactions related to cardiometabolic markers. In this study, we focus on the conceptual aspects, diagnostic criteria, as well as the role of genetics, particularly on SNPs and polygenic risk scores (PRS) for interindividual analysis. In addition, this review highlights future perspectives of personalized nutrition with regard to the approach of MetS and how individualized multiomics approaches could improve the current outlook.

The heterogeneity of metabolic syndrome presentation and challenges this causes in its pharmacological management: a narrative review focusing on principal risk modifiers

ABSTRACT Introduction Metabolic syndrome (MetS), i.e. the cluster of cardiometabolic risk factors comprising visceral obesity, impaired glucose metabolism, arterial hypertension and atherogenic dyslipidemia, is prevalent globally and exacts a heavy toll on health care expenditures. Areas covered The pathophenotypes of individual traits of the MetS in adults are discussed first, with strong emphasis on nonalcoholic fatty liver disease (NAFLD) and sex differences. Next, I discuss recent studies on phenotypic and outcome heterogeneity of the MetS, highlighting the role of NAFLD, sex, reproductive status, and depressive disorders. In the second half of the article, the therapeutic implications of the variable MetS types and features are analyzed, focusing on the most recent developments, and guidelines. Expert opinion I have identified physiological, pathological, social and medical sources of phenotypical heterogeneity in the MetS and its constitutive traits. Improved understanding of these variables may be utilized in the setting of future precision medicine approaches in the field of metabolic disorders and target organ damage.

THE IMPACT OF SEX ON METABOLIC AND FUNCTIONAL ABNORMALITIES, INDUCED BY HIGH-FRUCTOSE-DIET IN RATS

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, which manifestation may be different for men and women. Changes in sex hormone levels in men and women during lifespan contribute to increased cardiometabolic risk. Data of clinical researches suggest that transition from normal glucose tolerance to dysglycemia lead to more adverse differences in cardiometabolic risk factors in women than in men, suggesting an important impact of sex on the development of metabolic abnormalities. A significant increase in risk may be due to the sex differences in manifestation of some components of metabolic syndrome, but accurate reasons of these discrepancies need future investigations. The aim of this study was to determine the differences in impairment of glucose, lipid metabolism and cardiovascular systems function between male and female rats with different levels of estrogen sufficiency. Materials and Methods. MetS was modelled in male and female rats with different levels of estrogens by chronic (for 8 weeks) intake of fructose (high-fructose diet - HFD) with drinking water at a concentration 200 g/L. Estrogens deficiency was reproduced by bilateral ovariectomy. Experimental rats were divided into five groups: control males (n=6), control females (n=6), males with HFD (n=6), sham-operated females with intact ovaries and HFD (n=6), ovariectomized (OVX) females with HFD (n=6). Glucose homeostasis was assessed by basal glycemia, glycemia during the intra-abdominal glucose tolerance test and fructosamine level. Insulin sensitivity was determined using intra-abdominal insulin tolerance test. Body weight gain, visceral fats, level of total cholesterol, triglycerides, levels of estradiol and testosterone in blood serum were determined. At the end of the study, electrocardiograms were recorded in three standard leads from the limbs. Data are presented as mean ± standard error of mean (SEM). Results. It was established that HFD have not been induced metabolic abnormalities in female rats with intact ovaries. HFD, independently of sex, led to the development of insulin resistance and significant increase in fructosamine level in blood serum of rats. Ovariectomized females with HFD had greater intensity of body weight gain, significantly higher levels of relative mass of fats, more pronounced alterations of lipid metabolism with increased total cholesterol and significantly higher levels of triglycerides, than HFD-treated male rats. However, impairment of glucose tolerance, induced by HFD, was more pronounced in male than in OVX female rats. We found the decline testosterone levels and slight increase in estradiol levels in male rats with HFD. OVX females with HFD had a moderate significant increase in testosterone levels and dramatically decrease in estradiol concentration as result of bilateral ovariectomy. HFD, independently from sex, induced the development of sinus tachycardia in experimental animals. Metabolic abnormalities, induced by HFD, in OVX female rats led to more pronounced disturbances of heart depolarization and repolarization processes and development of diastolic dysfunction compare to HFD-treated males. Conclusions. We revealed that sex and estrogens levels have a great impact on the impairment of glucose and lipid metabolism and cardiovascular systems function, induced by high-fructose diet in rats. The obtained data justifies the necessity to take into account sex and estrogens sufficiency in the development of gender-specific prevention and treatment of metabolic syndrome.

Cardiometabolic risk factor clustering in persons with spinal cord injury: A principal component analysis approach

Context/Objective To identify cardiometabolic (CM) measurements that cluster to confer increased cardiovascular disease (CVD) risk using principal component analysis (PCA) in a cohort of chronic spinal cord injury (SCI) and healthy non-SCI individuals. Approach A cross-sectional study was performed in ninety-eight non-ambulatory men with chronic SCI and fifty-one healthy non-SCI individuals (ambulatory comparison group). Fasting blood samples were obtained for the following CM biomarkers: lipid, lipoprotein particle, fasting glucose and insulin concentrations, leptin, adiponectin, and markers of inflammation. Total and central adiposity [total body fat (TBF) percent and visceral adipose tissue (VAT) percent, respectively] were obtained by dual x-ray absorptiometry (DXA). A PCA was used to identify the CM outcome measurements that cluster to confer CVD risk in SCI and non-SCI cohorts. Results Using PCA, six factor-components (FC) were extracted, explaining 77% and 82% of the total variance in the SCI and non-SCI cohorts, respectively. In both groups, FC-1 was primarily composed of lipoprotein particle concentration variables. TBF and VAT were included in FC-2 in the SCI group, but not the non-SCI group. In the SCI cohort, logistic regression analysis results revealed that for every unit increase in the FC-1 standardized score generated from the statistical software during the PCA, there is a 216% increased risk of MetS (P = 0.001), a 209% increased risk of a 10-yr. FRS ≥ 10% (P = 0.001), and a 92% increase in the risk of HOMA2-IR ≥ 2.05 (P = 0.01). Conclusion Application of PCA identified 6-FC models for the SCI and non-SCI groups. The clustering of variables into the respective models varied considerably between the cohorts, indicating that CM outcomes may play a differential role on their conferring CVD-risk in individuals with chronic SCI.