Risk Of Metabolic Syndrome Research Articles

The Analysis of the Risk of Metabolic Syndrome and Physical Activity Participation in Stroke Patients: The National Health and Nutrition Survey (8th, 2019-2021)

OBJECTIVES The purpose of this study is to find out the correlation with the risk of metabolic syndrome in stroke patients using KNHNES data.METHODS The raw data from the 1st to 3rd years of the 8th National Health and Nutrition Survey (KNHANES) were used, and 290 stroke patients aged 60 or older (109 in 2019, 89 in 2020, 92 in 2021) were selected out of 22.559 participants. The average and standard deviation of the subjects' general characteristics were presented, the risk of stroke patients and metabolic syndrome and related variables were analyzed through Pearson’s correlation analysis(p<.05).RESULTS Men's fasting blood glucose was correlated with triglycerides (r=.175, p<.05), and HDL cholesterol was correlated with triglycerides (r=.-266, p<.05). Women's waist circumference was correlated with blood glucose (r=.321, p<.001), hypertension (r=.195, p<.05), and HDL cholesterol (r=.-205, p<.001). Fasting blood glucose was correlated with HDL cholesterol (r=.-265, p<.001) and triglyceride (r=.340, p<.001). HDL cholesterol was correlated with triglycerides (r=.-332, p<.001) and hypertension (r=.-195, p<.05).CONCLUSIONS In summary, the major independent factors for the risk of metabolic syndrome in stroke patients were triglyceride in men and fasting blood glucose and hypertension in women.

EXPLORING THE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND METABOLIC SYNDROME RISK IN YOUNG ADULTS: A REVIEW

Metabolic syndrome is a cluster of interrelated risk factors that increase the risk of cardiovascular disease and type 2 diabetes, particularly among young adults. Physical activity has been identified as a key lifestyle factor that can help mitigate the risk of developing metabolic syndrome. This review aims to synthesize the current evidence on the association between physical activity and metabolic syndrome risk in young adults. The review discusses the prevalence of metabolic syndrome in young adults and the various mechanisms by which physical activity can influence metabolic syndrome risk, including improvements in body composition, insulin sensitivity, lipid profile, and blood pressure regulation. Several studies have demonstrated that higher levels of physical activity, especially moderate-to-vigorous intensity exercise, are associated with a lower risk of metabolic syndrome in young adult populations. However, the relationship between physical activity and metabolic syndrome risk may be moderated by factors such as sex and socioeconomic status. The review also highlights the need for further research to better understand the long-term impact of physical activity, the optimal types and intensities of exercise, and the development of tailored interventions to promote sustained physical activity and improve metabolic health in young adults. In conclusion, this review emphasizes the importance of encouraging and supporting young adults to engage in regular physical activity as a strategy for the prevention and management of metabolic syndrome. Promoting physically active lifestyles among this population should be a public health priority to address the growing burden of metabolic syndrome and its associated health consequences.

Investigation of the interaction between genetic risk score (GRS) and fatty acid quality indices on metabolic syndrome among overweight and obese women

Background and aimMetabolic syndrome is one of the major public-health challenges, affecting one-quarter of the world population. Fatty acid quality indices are novel determinants of this disease and their interactions with genetic factors may have an impact on metabolic syndrome risk. Therefore, we aimed to investigate the interaction between genetic risk score (GRS) and fatty acid quality indices with metabolic syndrome (MetS) among overweight and obese women.MethodsIn the present cross-sectional study, 279 overweight and obese women (18–48 years old) were included. Several anthropometric measurements such as weight, height, body mass index (BMI), waist circumference (WC), and body fat percent (BF%) were measured. Also, systolic and diastolic blood pressure (SBP and DBP) were measured. Biochemical determination was performed for fasting blood glucose (FBS), triglyceride (TG), and high-density lipoprotein (HDL). MetS was determined according to National Cholesterol Education Program (NCEP ATP III) criteria. Dietary intake was evaluated by a validated and reliable 147-item semi-quantitative food frequency questionnaire. Cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (ω-6/ω-3) essential fatty acids were considered as fat quality indices. The salting-out method was used to extract the total DNA. The unweighted GRS was calculated using the risk alleles of the three single nucleotide polymorphisms. The total average GRS value was 2 and the sum of the risk alleles of the 3 polymorphisms was 6.ResultThe results of our analysis showed that after controlling for age, energy intake, BMI, and physical activity, there was a positive interaction between T2 of GRS and T2 of N6/N3 ratio on WC (β = 7.95, 95%CI = 0.83,15.08, P = 0.029), T3 of GRS and T2 of N6/N3 ratio on DBP (β = 5.93, 95%CI= -0.76,12.63, P = 0.083), and FBS (β = 6.47, 95%CI = 0.59,13.53, P = 0.073), T3 of GRS and T3 of N6/N3 ratio on TG (β = 54.42, 95%CI = 1.76,107.08, P = 0.043), and T3 of GRS and T3 of CSI on BF% (β = 3.55, 95%CI= -0.35,7.45, P = 0.075). Also T2 of GRS in the interaction with T3 of CSI leads to an decrease − 8.35 mg/dl in HDL level after adjustment in (β= -8.35, 95%CI= -17.34,0.62, P = 0.068).ConclusionIt seems the interaction of GRS and fatty acid quality indices is positively associated with several components of metabolic syndrome such as WC, TG and BF%. Our findings are of importance to public health, considering the high consumption of foods that are high on fatty acids. Conflicting evidence of many previous studies regarding the effect of fat intake and obesity and cardiovascular diseases could be because of the gene-diet interactions and genetic heterogeneity across various ethnic groups. Hence, the synergism effect of genetic and dietay intakes should be considered in future studies.

Association between the severity of hard-to-treat psoriasis and the prevalence of metabolic syndrome: A hospital-based cross-sectional study in Jakarta, Indonesia.

Psoriatic lesions on the scalp, face, intertriginous, genitals, palms/soles, and nails are often delay diagnosed, hard-to-treat, and cause disability. Metabolic syndrome (MetS) is one of the most frequent and significant comorbidities in psoriasis. Many studies have discovered a link between psoriasis and MetS, but none have specifically assessed the hard-to-treat psoriasis in Indonesian population. This is a multicenter study involving four dermatology referral hospitals to investigate the association between psoriasis severity that has hard-to-treat lesions with the prevalence of MetS in Jakarta, Indonesia. Data was collected from April to October 2022. The severity of 84 hard-to-treat psoriasis patients was measured by Psoriasis Area Severity Index (PASI) scores. The participants divided into PASI score >10 (severe) and ≤ 10 (mild-moderate) groups. MetS was identified based on the modified National Cholesterol Education Program Adult Treatment Panel III. MetS was found in 64.3% of patients. Patients with a PASI score>10 had a significantly higher risk of metabolic syndrome compared to those with a score ≤ 10 (78.6% vs 50%, OR 3.667; 95% CI 1.413-9.514; p = 0.006). The prevalence of hypertension (p = 0.028), low levels of high-density lipoprotein (HDL) cholesterol (p = 0.01), mean fasting blood sugar (p = 0.018), and triglyceride levels (p = 0.044) between the two groups differed significantly. This study found most frequent components of MetS were abdominal obesity, decreased levels of HDL cholesterol, hypertension, hyperglycemia, and hypertriglyceridemia respectively. Individuals with severe hard-to-treat psoriasis had a 3.67 times more likely to have MetS rather than the mild-moderate group.

Using propensity score matching analysis to compare between cardiometabolic risk factors and physical activity type in Korean adults: findings from a nationwide population-based survey

PurposeWe aimed to assess the effects of different exercise modalities on cardiometabolic risk factors within a comprehensive, representative sample of the Korean population.MethodsWe categorized 13,971 adult participants into aerobic exercise (AE), resistance exercise (RE), combined aerobic and resistance exercise (TE), insufficient exercise, and inactive groups. Multivariable regressions were conducted to compare the incidence of chronic diseases across the groups before and after propensity score matching (PSM).ResultsThe TE and RE groups had significantly lower waist circumference (WC), mean blood pressure (BP), glucose and insulin-related indices, and white blood cell count (WBC) measures, with TE showing the most significant differences. The TE group had significantly lower triglyceride levels and higher high-density lipoprotein-cholesterol levels. Post-PSM, the TE group had the lowest risk for metabolic syndrome, hypertension, and diabetes, closely followed by the RE group when compared with the inactive group. In a subgroup analysis, RE consistently exhibited benefits including lower body mass index, WC, BP, total cholesterol, glucose and insulin-related indices, and WBC count when compared with AE. RE may be associated with reduced incidence of cardiometabolic diseases compared to AE alone.ConclusionTE appears to be associated with significant reduction in cardiometabolic risk in Korean adults. RE possibly provides a more favorable cardiometabolic effect than AE.

Robust metabolic syndrome risk score based on triangular areal similarity.

One of the limitations of currently-used metabolic syndrome (MetS) risk calculations is that they often depend on sample characteristics. To address this, we introduced a novel sample-independent risk quantification method called 'triangular areal similarity' (TAS) that employs three-axis radar charts constructed from five MetS factors in order to assess the similarity between standard diagnostic thresholds and individual patient measurements. The method was evaluated using large datasets of Korean (n = 72,332) and American (n = 11,286) demographics further segmented by sex, age, and race. The risk score exhibited a strong positive correlation with the number of abnormal factors and was closely aligned with the current diagnostic paradigm. The proposed score demonstrated high diagnostic accuracy and robustness, surpassing previously reported risk scores. This method demonstrated superior performance and stability when tested on cross-national datasets. This novel sample-independent approach has the potential to enhance the precision of MetS risk prediction.

The Benefits of the Mediterranean Diet on Inflamm-Aging in Childhood Obesity.

(1) Background: Numerous elements of the Mediterranean diet (MD) have antioxidant and anti-inflammatory qualities. (2) Methods: We present a narrative review of the potential benefits of the Mediterranean dietary pattern (MD) in mitigating aging-related inflammation (inflamm-aging) associated with childhood obesity. The mechanisms underlying chronic inflammation in obesity are also discussed. A total of 130 papers were included after screening abstracts and full texts. (3) Results: A complex interplay between obesity, chronic inflammation, and related comorbidities is documented. The MD emerges as a promising dietary pattern for mitigating inflammation. Studies suggest that the MD may contribute to weight control, improved lipid profiles, insulin sensitivity, and endothelial function, thereby reducing the risk of metabolic syndrome in children and adolescents with obesity. (4) Conclusions: While evidence supporting the anti-inflammatory effects of the MD in pediatric obesity is still evolving, the existing literature underscores its potential as a preventive and therapeutic strategy. However, MD adherence remains low among children and adolescents, necessitating targeted interventions to promote healthier dietary habits. Future high-quality intervention studies are necessary to elucidate the specific impact of the MD on inflammation in diverse pediatric populations with obesity and associated comorbidities.

Pre-Pregnancy Obesity and Infants' Motor Development within the First Twelve Months of Life: Who Is Expected to Be the Ultimate Carrier of the Obesity Burden?

Pre-pregnancy obesity is a significant public health concern with profound implications for maternal and child health. The burgeoning evidence suggests that maternal obesity prior to conception is intricately linked with an increased risk of gestational complications, as well as with adverse neonatal outcomes. Furthermore, the long and short-term health of offspring, including the risk of early motor development impairment, obesity, and metabolic syndrome in childhood and adulthood, may be adversely affected as well. Addressing pre-pregnancy obesity is critical for improving overall maternal and child health outcomes, and therefore, the aim of this study was to evaluate the connections linking pre-pregnancy obesity with infants' motor development within the first twelve months of infants' lives. This study included 200 mother-infant pairs divided into two groups based on their pre-pregnancy body mass index values. To assess infants' early motor development, we used the Alberta Infant Motor Scale (AIMS) and evaluated the parameters of infants' early motor development at the ages of three, six, nine, and twelve months. Pre-pregnancy overweight/obesity was significantly associated with excessive gestational weight gain (p < 0.001), fetal macrosomia (p = 0.022), and a family history of diabetes and cardiovascular diseases (p = 0.048 and p = 0.041, respectively), as well as with all observed parameters of early motor development at the ages of three, six, nine, and twelve months: AIMS 3 months total (p < 0.001), AIMS 6 months total (p < 0.001), AIMS 9 months total (p < 0.001), and AIMS 12 months total (p < 0.001). Furthermore, pre-pregnancy overweight/obesity was a significant predictor for AIMS 6 months total (p = 0.043) and AIMS 6 months supination (p = 0.017). Pre-pregnancy obesity is a critical determinant of pregnancy outcomes and offspring early motor development, with possible far-reaching implications for children's long-term well-being. Addressing this issue requires a comprehensive approach that includes preconception weight management, targeted interventions during the pregnancy and postpartum periods, and ongoing research to better understand the underlying mechanisms and develop effective strategies for prevention and management.

Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case–control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients. A cohort of 90 sarcoidosis patients and a cohort of 90 control subjects were enrolled. Clinical, anamnestic, and biochemical data were collected. Results showed that TyG index values were higher in the sarcoidosis cohort than in the control group (p < 0.001), even after excluding the influence of diabetes and metabolic syndrome (p = 0.018). In the sarcoidosis cohort, TyG index was not correlated with clinical phenotyping (p = 0.358), gender (p = 0.139), radiological stage (p = 0.656), glucocorticoids cumulative dose (p = 0.682) or treatment regimen (p = 0.093), while significant positive correlations with waist circumference (p < 0.001), systolic and diastolic pressure (p = 0.041 and p = 0.029, respectively), Framingham score (p = 0.007) were found. Receiving operating characteristics curve analysis identified a TyG index optimal cut-off value of 8.64 (66.7% sensitivity, 77.8% specificity, area under the curve -AUC- 75%, 95% confidence interval -CI- 65–85, p < 0.001) to detect metabolic syndrome and a cut-off value of 8.69 (64.1% sensitivity, 70.6% specificity; AUC 67%, 95% CI 55–78, p = 0.007) to detect an intermediate cardiovascular risk according to Framingham risk score. Concluding, TyG index can be considered a useful tool for the metabolic assessment of sarcoidosis patients, given its capacity to predict metabolic syndrome and cardiovascular risk.

Preconceptional maternal hyperandrogenism and metabolic syndrome risk in male offspring: a long-term population-based study.

There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life. Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons. There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18),P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1). The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring.

Body composition and motor function in children born large for gestational age at term.

This cross-sectional study compared body composition and motor function between children who were born large for gestational age (LGA) and those born appropriate for gestational age (AGA) and to investigate the association between gait quality and other variables. Body composition was determined using a bioelectrical impedance analyzer. Motor functions were assessed using one-leg standing time, timed up-and-go test, five times sit-to-stand test, and three-dimensional gait analysis. We compared the results between two groups. We performed multiple regression analysis to evaluate the association between gait deviation index and variables of LGA, fat mass index, and motor functions (adjusted for age and sex). Children aged 6-12 years who were born LGA at term (n = 23) and those who were born AGA at term (n = 147) were enrolled. The LGA group had a higher fat mass index (2.9 vs. 2.2, p = 0.006) and lower gait deviation index (91.4 vs. 95.4, p = 0.011) than the AGA group. On multiple regression analysis, gait deviation index was associated with being LGA and fat mass index. In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function. Children aged 6-12 years who were born large for gestational age (LGA) at term showed a higher fat mass index and lower gait deviation index than those who were born appropriate for gestational age at term. No significant differences in balance function or muscle strength were observed between groups. On multiple regression analysis, gait deviation index was associated with being LGA at birth and fat mass index. In school-aged children who were born LGA, monitoring increased fat mass index and decreased gait deviation index could lessen the risk of metabolic syndrome and reduced gait function.

Positive association between blood ethylene oxide levels and metabolic syndrome: NHANES 2013-2020.

The exposure of Ethylene oxide (EO) is linked to systemic inflammatory response and various cardiovascular risk factors. Hemoglobin's binding to ethylene oxide (HbEO) was used to measure serum EO level. This research aims to explore the association between metabolic syndrome (MetS) and HbEO, and between HbEO and components of metabolic syndrome. This research included 1842 participants from 2013 to 2020 in National Health and Nutrition Examination Survey (NHANES) database. Weighted logistic regression models were used to analyze the relationship between HbEO and metabolic syndrome risk, using odds ratio (OR) and 95% confidence interval (CI). The restricted cubic spline plot explores whether there is a dose-response relationship between HbEO and MetS risk. Subgroup analysis was performed to analyze study heterogeneity. Significant differences were found in gender, educational level, marital status, diabetes status and hypertension among different groups (P < 0.001, P = 0.007, P = 0.003, P < 0.001, P < 0.001, respectively). The serum HbEO level exhibited positive correlation with metabolic syndrome risk in Q2 level (OR=1.64, 1.04~2.48), Q3 level (OR=1.99, 1.29~3.08), and Q4 level (OR=2.89, 1.92~4.34). The dose-response association suggested a possible linear association between serum HbEO and metabolic syndrome risk (P-overall=0.0359, P-non-linear=0.179). L-shaped association was found between HbEO and the risk of MetS in female population, obese population and mid-age and elder population (P-overall<0.001, P-non-linear=0.0024; P-overall=0.0107, P-non-linear=0.0055 P-overall<0.001 P-non-linear=0.0157). This study indicates a linear correlation between MetS and HbEO, with MetS risk escalating as HbEO levels increase. The prevalence of MetS varies depending on BMI, age and gender, and these factors can also influence MetS prevalence when exposed to EO.

Assessing the predictive value of insulin resistance indices for metabolic syndrome risk in type 2 diabetes mellitus patients

Limited research has explored the effectiveness of insulin resistance (IR) in forecasting metabolic syndrome (MetS) risk, especially within the Iranian population afflicted with type 2 diabetes mellitus (T2DM). The present investigation aimed to assess the efficacy of IR indices in predicting the risk of MetS among T2DM patients. Convenient sampling was utilized to select four hundred subjects with T2DM. Metabolic factors and IR indices, including the Waist Circumference-Triglyceride Index (WTI), Triglyceride and Glucose Index (TyG index), the product of TyG index and abdominal obesity indices, and the Metabolic Score for Insulin Resistance (METS-IR), were evaluated. Logistic regression, coupled with modeling, was employed to explore the risk of MetS. The predictive performance of the indices for MetS stratified by sex was evaluated via receiver operating characteristic (ROC) curve analysis and estimation of the area under the curve (AUC) values. The TyG-Waist Circumference (TyG-WC) index exhibited the largest AUCs in both males (0.91) and females (0.93), while the TyG-Body Mass Index (TyG-BMI) demonstrated the smallest AUCs (0.77 in males and 0.74 in females). All indices significantly predicted the risk of MetS in all subjects before and after adjustment (p < 0.001 for all). The TyG-WC index demonstrated the highest odds ratios for MetS (8.06, 95% CI 5.41–12.00). In conclusion, all IR indices assessed in this study effectively predicted the risk of MetS among Iranian patients with T2DM, with the TyG-WC index emerging as the most robust predictor across both genders.

A meta-analysis of the association between RBP4 rs3758539 genotype and metabolic syndrome factors.

To explore the link between the RBP4 rs3758539 genotype and metabolic syndrome risk factors and whether the impact of this genetic variation displays any potential race discrepancy. This meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (registration no. CRD42023407999). PubMed, Web of Science, Embase, Cochrane Library, Google Scholar, Airiti Library and CINAHL databases were used for the study search until October 2023. We evaluated the methodological quality using the Joanna Briggs Institute checklist and determined the correlation using a random-effects meta-analysis. The results indicated that individuals with the rs3758539 GA/AA genotype had a higher risk profile, including lower high-density lipoprotein levels [correlation: -0.045, 95% confidence interval (CI): -0.080 to -0.009, p = .015, I2 = 46.9%] and higher body mass index (correlation: 0.117, 95% CI: 0.036-0.197, p = .005, I2 = 82.0%), body fat (correlation: 0.098, 95% CI: 0.004-0.191, p = .041, I2 = 64.0%), and low-density lipoprotein levels (correlation: 0.074, 95% CI: 0.010-0.139, p = .024, I2 = 0%), of developing metabolic syndrome than those with the GG genotype. The subgroup analysis maintained a significantly positive correlation between the rs3758539 GA/AA genotype and body mass index (correlation: 0.163, 95% CI: 0.031-0.289, p = .016, I2 = 88.9%) but a negative correlation with high-density lipoprotein levels (correlation: -0.047, 95% CI: -0.087 to -0.006, p = .025, I2 = 65.7%) in the Asian group only. The current meta-analysis supports a significant link between the RBP4 rs3758539 GA/AA genotype and the metabolic syndrome.

Law Enforcement Officers Have an Increased Prevalence of Subclinical Cardiovascular Disease That Is Not Explained by Traditional Risk Factors.

The aim of the study is to determine if law enforcement officers develop subclinical atherosclerotic cardiovascular disease (ASCVD) earlier than nonofficers and, if so, the extent to which conventional risk factors explain this difference. Methods: Estimated pulse wave velocity (ePWV) was the marker of subclinical ASCVD. EPWV, ASCVD risk factors, metabolic syndrome (MetS), and 10-year risk for ASCVD were compared among 408 law enforcement officers and a civilian cohort. Results: EPWV, 10-year ASCVD risk, and MetS prevalence increased significantly with age. All but the officers age 55 and older had higher ePWV cohort than the civilian cohort ( P < 0.001). Ten-year ASCVD risk explained the most variability of ePWV ( R2 = 0.49, P < 0.001). Conclusions: Officers develop subclinical ASCVD earlier than nonofficers. Conventional ASCVD risk factors only explain about half of this increase. Occupational factors may play a role in contributing to this increased ASCVD risk.

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis.

Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.

Depression, Anxiety, and Risk of Metabolic Syndrome in Women With Polycystic Ovary Syndrome: A Longitudinal Study.

Patients with PCOS are at high risk of depression, anxiety, and metabolic syndrome (MetSyn), a key predictor of cardiovascular disease. The impact of depression and/or anxiety on MetSyn is unknown in this population. To compare the risk of developing MetSyn in patients with PCOS with and without a history of depression and/or anxiety. Retrospective longitudinal cohort study (2008-2022) with median follow-up of 7 years. Tertiary care ambulatory practice. Patients with hyperandrogenic PCOS and at least 2 evaluations for MetSyn ≥3 years apart (n=321). N/A. The primary outcome was risk of developing MetSyn. We hypothesized that this risk would be higher with a history of depression and/or anxiety. At the first visit, 33.0% had a history of depression and/or anxiety, with a third prescribed antidepressants or anxiolytics. Depression and/or anxiety increased risk of developing MetSyn during the study period (adjusted hazard ratio [aHR] 1.45, 95% CI 1.02-2.06, p=0.04) with an incidence of MetSyn of 75.3 compared to 47.6 cases per 100 person-years among those without (p=0.002). This was primarily driven by depression (aHR 1.56, 95% CI 1.10-2.20, p=0.01). Patients with PCOS and depression and/or anxiety have a high risk of developing MetSyn, with a stronger association between depression and MetSyn. Our findings highlight the urgent need for guideline-directed screening for depression and anxiety at time of diagnosis of PCOS as well as screening at subsequent visits to facilitate risk stratification for metabolic monitoring and early intervention in this high-risk group.

Relationship between METS-IR and thyroid cancer incidence in Korea: a nationwide population-based study.

Several previous studies found a positive relationship between metabolic syndrome (MetS) and thyroid cancer (TC) risk. However, there is no research that has studied the relationship between the metabolic score for insulin resistance (METS-IR), a novel surrogate marker for IR, and TC incidence. Thus, we designed this retrospective cohort study to evaluate the relationship between the incidence of TC and METS-IR. We analyzed a cohort of 314,321 Korean adults aged over 40 years who participated in the National Health Screening Program from 2009 to 2010. The individuals were divided into four groups based on METS-IR quartiles. Follow-up was until the diagnosis of TC or death, or until December 31, 2019, if neither. The relationship between METS-IR and TC incidence was analyzed using the Cox proportional-hazards model with multi-variable adjustments. A total of 4,137 participants (1.3%) were diagnosed with TC during a mean follow-up of 9.5 ± 1.5 years. The population with Q1 METS-IR scores showed higher disease-free probabilities than those with Q4 METS-IR scores (p <0.001). The hazard ratio (95% confidential interval) for TC incidence in Q2, Q3, and Q4 METS-IR value were 1.14 (1.05 to 1.25), 1.21 (1.11 to 1.33), and 1.30 (1.18 to 1.42) compared with Q1 of METS-IR, respectively. The incidence of TC tended to increase with increasing METS-IR values in the total population, especially the male population in the restricted cubic spline. In subgroup analysis, the TC risk was more pronounced in the subgroups under 65 and with a BMI < 25 kg/m2. METS-IR was positively correlated with TC incidence in Korea.

Epigenetic/circadian clocks and PCOS.

Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women. It is associated with increased risks of metabolic syndrome, Type 2 diabetes, cardiovascular diseases, mood disorders, endometrial cancer and non-alcoholic fatty liver disease. Although various susceptibility loci have been identified through genetic studies, they account for ∼10% of PCOS heritability. Therefore, the etiology of PCOS remains unclear. This review explores the role of epigenetic changes and modifications in circadian clock genes as potential contributors to PCOS pathogenesis. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNA changes, have been described in diseases related to PCOS, such as diabetes, cardiovascular diseases, and obesity. Furthermore, several animal models have illustrated a link between prenatal exposure to androgens or anti-Müllerian hormone and PCOS-like phenotypes in subsequent generations, illustrating an epigenetic programming in PCOS. In humans, epigenetic changes have been reported in peripheral blood mononuclear cells (PBMC), adipose tissue, granulosa cells (GC), and liver from women with PCOS. The genome of women with PCOS is globally hypomethylated compared to healthy controls. However, specific hypomethylated or hypermethylated genes have been reported in the different tissues of these women. They are mainly involved in hormonal regulation and inflammatory pathways, as well as lipid and glucose metabolism. Additionally, sleep disorders are present in women with PCOS and disruptions in clock genes' expression patterns have been observed in their PBMC or GCs. While epigenetic changes hold promise as diagnostic biomarkers, the current challenge lies in distinguishing whether these changes are causes or consequences of PCOS. Targeting epigenetic modifications potentially opens avenues for precision medicine in PCOS, including lifestyle interventions and drug therapies. However, data are still lacking in large cohorts of well-characterized PCOS phenotypes. In conclusion, understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS in the future.

Abstract LB149: Metabolic syndrome and obesity-related cancer risk and survival: An umbrella review

Abstract Background: Recent evidence suggests that metabolic syndrome (MetS) may be a potential risk factor for obesity-related cancer (ORC) owing to shared risk factors like physical inactivity, hyperglycemia, insulin resistance, gut microbiome dysfunction, and inflammation. We conducted an umbrella review of systematic reviews with meta-analysis to synthesize the evidence on the association between MetS and ORC incidence and survival. Methods: The study protocol was registered with PROSPERO (CRD42021230899). Searches in five databases (Medline, Embase, CINAHL, Cochrane Library, and Scopus) retrieved 2,524 systematic reviews with meta-analyses (SRMA) after duplicates were removed. SRMA were eligible if they evaluated MetS with ORC incidence or survival, were conducted in an adult population (≥18 years), and included the pre-defined study-specific data. Using Covidence, two reviewers independently screened titles and abstracts (2,524) and then reviewed full text (41), selecting 23 SRMAs for inclusion. Data extraction was then completed independently by two reviewers. The outcomes were pooled using a random-effects model with the package “meta” in R. Sub-group analyses were conducted for a priori chosen factors, as outlined in the protocol. SRMA were appraised using the AMSTAR 2 criteria. Results: 23 SRMA published between 2001 and 2023 met our inclusion criteria, comprising a total of 112 studies, ~52,543,335 total individuals, and ~355,808 ORC cases. After pooled analyses, MetS was associated with a statistically significant 10% increased risk of ORC [RR(95% CI): 1.10(1.06-1.14)]. MetS was also statistically significantly associated with poorer ORC-specific survival [RR(95% CI): 1.10(1.02-1.18)], though there was no association between MetS and overall survival [RR(95% CI): 1.04(0.97-1.11)]. When stratified by sex, both male and female individuals with MetS had a statistically significant higher risk of ORC [RR(95% CI): 1.12(1.06-1.17), 1.10(1.01-1.19), respectively]. When stratified by cancer site, individuals with MetS demonstrated a higher risk of colorectal cancer [RR(95% CI): 1.12(1.06-1.18)]. We also observed suggestive associations between MetS and liver, pancreatic, and postmenopausal breast cancer risk, but these were not statistically significant [RR(95% CI): 1.20(1.00-1.45), 1.20(0.96-1.50), 1.12(0.99-1.27), respectively]. All associations were supported by “critically low” quality evidence according to the AMSTAR2 criteria. This was primarily because these SRMAs either did not follow a pre-specified written and published protocol, or did not provide a list of all potentially relevant studies that were read in full-text form but excluded from the review. Conclusions: These results emphasize the important role that MetS may play in the development of ORC as well as in the survival of patients with ORC. Conducting high-quality reviews is needed to increase the certainty of evidence, reduce potential bias, and improve knowledge in this field. Citation Format: Maci Winn, Prasoona Karra, Ryzen Benson, Svenja Pauleck, Nathorn Chaiyakunapruk, Win Khaing, Tallie Casucci, Mary M. McFarland, Siwen Hu-Lieskovan, Michelle Litchman, Yizhe Xu, Mary Playdon, Sheetal Hardikar. Metabolic syndrome and obesity-related cancer risk and survival: An umbrella review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB149.