Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Handgrip strength, and erectile dysfunction among men with metabolic syndrome attending an institutional primary care clinic in Malaysia: A cross-sectional study.

Background: Erectile dysfunction (ED) is an independent predictor for cardiovascular diseases (CVD). The prevalence increases with age, but little is known about the relationship between handgrip strength (HGS) and ED, especially among men with a high risk of CVD. This study aimed to determine the prevalence of ED among men aged ≥40 years with metabolic syndrome (MetS) and its association with HGS. Materials and Methods: A cross-sectional study at an institutional primary care clinic in Malaysia was conducted between June 2021 and October 2021. HGS and erectile function were assessed using a hand dynamometer and International Index of Erectile Function (IIEF-5) questionnaire, respectively. Multiple logistic regression analyses were performed to determine the association between sociodemographics, clinical characteristics, and HGS with ED. Results: A total of 334 participants were recruited. The prevalence of ED was 79% (95% confidence interval [CI]: 0.75-0.84). ED was associated with elderly aged ≥60 years (odds ratio [OR] 3.27, 95%CI: 1.60-6.69), low HGS (OR 15.34, 95%CI: 5.64-41.81) and high total cholesterol (OR 0.36, 95%CI: 0.16-0.78). Conclusion: In conclusion, age above 60 years and those with low HGS are at higher risk of ED. Thus, robust screening of ED among men with MetS and improving muscle strength and physical fitness may be warranted.

Body composition, metabolic syndrome, and lifestyle in treatment-naïve gender-diverse youth in Israel.

BACKGROUND: There is a scarcity of published studies evaluating transgender/gender-diverse youth before initiating gender-affirming hormones. AIM: To study the body composition, metabolic syndrome (MetS) components and lifestyle habits in treatment-naïve transgender youth. METHODS: Cross-sectional study evaluating 153 transgender youth [median age 15.7 years, 94 transgender males] who attended The Israeli Children and Adolescents Gender Clinic between 6/2021-12/2022. Clinical, metabolic data and lifestyle habits (diet, physical activity and sleep patterns) were retrieved from the medical files. Body composition was determined by bioelectrical impedance analysis. Body mass index and muscle-to-fat ratio z-scores were calculated by sex designated at birth. RESULTS: Weight categories differed between genders, with a greater proportion of subjects classified as underweight among transgender females, and a greater proportion affected by overweight/obese/severe obese among transgender males (p = 0.035). The odds for MetS components were increased by 2.2 for every 1 standard deviation decrease in the muscle-to-fat ratio z-score (95%CI: 1.45 to 3.26, p < 0.001). About one-third of the cohort did not meet any of the three lifestyle recommendations. Transgender males had increased odds for MetS components by 3.49 (95%CI: 1.63 to 7.44, p = 0.001). CONCLUSIONS: Treatment-naïve transgender-male adolescents have an imbalance between muscle and adipose tissue, which places them at increased susceptibility for MetS components even prior to hormonal treatment.

The impact of metabolic syndrome on clinical outcomes following total knee arthroplasty in osteoarthritis patients.

Background: Metabolic syndrome (MetS) is a combination of interconnected conditions, including insulin resistance, abdominal obesity, high blood pressure, and abnormal blood lipid levels. The objective of this research was to investigate the impact of MetS on the quality of life and clinical outcomes following total knee arthroplasty (TKA) in patients with osteoarthritis (OA). Methods: A retrospective descriptive study was conducted to enroll OA patients who underwent primary TKA at Zhongda Hospital, Southeast University from January 2015 to August 2019. A total of 83 OA patients who did and 144 (MetS group) who did not have MetS (non-MetS group) were included. An analysis was conducted on the patient's clinical data. Results: The two groups had similar results in terms of lengths of stay (P=0.93), hospital costs (P=0.24), and overall complication rates (P=0.99). There was no significant difference in the average erythrocyte sedimentation rate and C-reactive protein levels between the groups. However, the MetS group exhibited notably lower Hospital for Special Surgery knee scores and Short Form [36] health survey (SF-36) scores compared to the non-MetS group (both P>0.05) during the one-year follow-up period. Conclusions: OA patients who have MetS had significantly worse knee joint function and quality of life after TKA. There are certain constraints in the current research. First, it belongs to a single-center retrospective study. Further study will be necessary to determine the generality of this conclusion. Second, this study is retrospective, and the number of patients included is not large. Third, due to the diverse clinical groups in our hospital, it is challenging to comprehensively document all the clinical data of the patients involved in this study. Forth, this study did not compare the preoperative differences between the two groups, as well as analyze the postoperative improvement changes in depth. We will compare the preoperative and postoperative differences between the two groups in more depth in future large sample studies.

Association of the visceral fat metabolic score with osteoarthritis risk: a cross-sectional study from NHANES 2009-2018.

BACKGROUND: Currently, obesity has been recognized to be an independent risk factor for osteoarthritis (OA), and the Metabolic Score for Visceral Fat (METS-VF) has been suggested to be potentially more accurate than body mass index (BMI) in the assessment of obesity. Nevertheless, the correlation of METS-VF with OA has not been obviously revealed yet. Therefore, this study aimed to delve into the potential relationship between METS-VF and OA. METHODS: By examining data from the NHANES (2009-2018), weighted multivariate logistic regression analyses were used for assessing the correlation between METS-VF and OA. Subgroup analyses were then performed to validate the findings. Moreover, the nonlinear relationship between the two was assessed by restricted cubic spline (RCS). Receiver operating characteristic (ROC) curves were plotted to examine the diagnostic accuracy of METS-VF versus previous obesity index for OA. RESULTS: This study involved 7639 participants. According to our results, METS-VF was notably related to an elevated risk of OA, regardless of the METS-VF and the trend of positive association was more pronounced with the elevating METS-VF level (p for trend < 0.05). Subgroup analyses showed that the positive association between METS-VF and prevalence of osteoarthritis persisted in all populations with different characteristics, confirming its validity in all populations. Besides, RCS results showed a significant non-linear relationship between METS-VF and OA (p-non-linear < 0.05). As indicated by the ROC curve analysis results, METS-VF was a superior predictor of OA to BMI and HC. CONCLUSIONS: This study finds a possible nonlinear positive correlation between METS-VF and the risk of OA. In addition, METS-VF may serve as an indicator for the more accurate diagnosis of OA and provide a new way to further evaluate the relationship between visceral fat and OA.

Association of weight-adjusted waist index with cardiovascular disease and mortality among metabolic syndrome population.

Metabolic syndrome (MetS) is prevalent and significantly impacts global public health, with obesity being a major risk factor for cardiovascular diseases (CVD) and mortality. Traditional metrics like body mass index (BMI) have limitations in assessing obesity-related risks. The weight-adjusted waist circumference index (WWI) has emerged as a novel obesity metric, this study aimed to evaluate the association of WWI with CVD and mortality in MetS patients. This study used data from 12,641 participants with MetS, derived from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2020. The WWI was calculated, and its association with CVD and mortality was assessed using multivariate logistic and Cox regression models. The study controlled for potential confounders and performed subgroup and sensitivity analyses to validate the robustness of the findings. The predictive performance of WWI was evaluated using the area under the receiver operating characteristic curve (ROC). Kaplan-Meier (KM) curves further were used to evaluate the associations between WWI and mortality of the MetS population. As WWI values escalated, there was a proportional rise in the risk of CVD and mortality in MetS. The fully adjusted continuous model revealed a 32.0% elevated likelihood of CVD development, a 69.5% increased probability of heart failure (HF), a 51.1% heightened risk for CVD mortality, and a 22.8% augmented risk for all-cause mortality with each one-unit increment in WWI. Comparing the highest to the lowest quartile of WWI, the top quartile exhibited a significantly increased risk of CVD (odds ratio [OR] = 1.883; 95% confidence interval [CI]: 1.276-2.633, p-value = 0.001), HF (OR = 2.909; 95% CI: 1.490-5.677, p-value = 0.002), CVD mortality (hazard ratio [HR] = 2.088; 95% CI: 1.279-3.409, p-value = 0.003), and all-cause mortality (HR = 1.394; 95% CI: 1.070-1.816, p-value = 0.014) among individuals with MetS. Sensitivity and subgroup analyses substantiated the consistency and stability of these associations across various demographic groups. The ROC analysis demonstrated that WWI outperforms BMI in predicting adverse outcomes in MetS. The KM curves validated that higher WWI values was correlated with diminished survival rates in MetS population. The WWI served as a significant indicator for assessing the risk of CVD and mortality in the MetS population. This study recommended the regular assessment of WWI in MetS individuals for evaluating their risk of CVD and mortality, potentially enhancing preventive and treatment strategies for this patient population.

Regulation of Monocyte Apoptosis and DNA Extrusion in Monocyte Extracellular Traps by PSGL-1: Relevance in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by severe organ damage and lacking curative treatment. While various immune cell types, especially dysfunctional B and T cells and neutrophils, have been related with disease pathogenesis, limited research has focused on the role of monocytes in SLE. Increased DNA extracellular traps, apoptosis and necrosis have been related to lupus pathogenesis. Our goal is to analyze the contribution of P-selectin glycoprotein ligand 1 (PSGL-1) in SLE monocytes to disease pathogenesis by investigating the control exerted by PSGL-1 on monocyte apoptosis and DNA extrusion in extracellular traps (METs). Monocytes from active disease patients (aSLE) exhibited reduced levels of PSGL-1. Importantly, lower PSGL-1 levels in SLE monocytes associated with several clinical characteristics, including anti-dsDNA autoantibodies, lupus anticoagulant, clinical lung involvement, and anemia. Monocytes from SLE patients showed higher susceptibility to apoptosis than healthy donors (HD) monocytes and PSGL-1/P-selectin interaction decreased secondary necrosis in HD but not in aSLE monocytes. Regarding METs, aSLE monocytes exhibited higher susceptibility to generate METs than HD monocytes. The interaction of HD monocytes with P-selectin induced Syk activation and reduced the levels of DNA extruded in METs. However, in aSLE monocytes, PSGL-1/P-selectin interaction did not activate Syk or reduce the amount of extruded DNA. Our data suggest a dysfunctional PSGL-1/P-selectin axis in aSLE monocytes, unable to reduce secondary necrosis or the amount of DNA released into the extracellular medium in METs, potentially contributing to lupus pathogenesis.

Sex- and Age-Specific Associations Between Metabolic Syndrome and Future Functional Disability in the Japanese Older Population.

Whether the association between metabolic syndrome (MetS) and functional disability differs depending on sex or age remains unknown. To determine the association between MetS and functional disability in older people separately by sex and age groups. A total of 11 083 participants (4407 men and 6676 women) aged 65 years or over without functional disability were enrolled. MetS was defined according to the revised NCEP ATP III guidelines. Functional disability was defined by a new certification in the long-term care insurance in Japan. Cox proportional hazards models were used to assess the risk of functional disability with adjustment for possible confounding factors. Over the mean observation period of 10.5 years, 1282 men and 2162 women experienced functional disability. For those aged 65 to 74 years, HRs (95% CIs) for functional disability in the MetS group were 1.33 (1.07-1.66) in men and 1.15 (1.000-1.32) in women. For those aged 75 years or older, there was no significant association in men or women. In subjects with a severe care need level, there was a marginal significant association in men aged 65 to 74 years. Among the MetS components that independently increased the risk of functional disability were glucose intolerance and elevated blood pressure (men and women aged 65-74 years), obesity (women aged 65-74 years), and glucose intolerance (women aged 75 years or older). MetS contributed to an increase in a high risk of future functional disability among individuals aged 65 to 74 years. In this age group, improvement of lifestyle, health promotion and interventions for MetS from middle age may prevent future functional disability.

Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank.

PURPOSE: This study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer. METHODS: A total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). RESULTS: Ten years after recruitment, 0.16% (95%CI 0.11-0.26%) had esophageal cancer and 4.17% (95%CI 3.86-4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C. CONCLUSION: TyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification.

Association between Serum Vitamin D Status and Circadian Syndrome: A Cross-Sectional Study.

BACKGROUND: Circadian Syndrome (CircS) encompasses cardiometabolic risk factors and comorbidities, indicating an elevated susceptibility to cardiovascular disease and type 2 diabetes. METHODS: This cross-sectional study aimed to investigate the association between vitamin D levels and each of the following: CircS, metabolic syndrome (MetS), and the individual components of CircS. Data from 14,907 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018 were utilized. CircS was defined based on MetS components, alongside depression, short sleep, and non-alcoholic fatty liver disease (NAFLD). RESULTS: Our results indicated that low vitamin D levels exhibited meaningful associations with CircS, with vitamin D deficiency and inadequacy demonstrating 2.21-fold (95% CI 1.78-2.74, p < 0.001) and 1.33-fold (95% CI 1.14-1.54, p < 0.001) increases in CircS odds, respectively. The association between vitamin D deficiency and CircS was stronger than that with MetS. Additionally, a dose-response gradient in odds of CircS components, particularly with short sleep duration, was noted as serum vitamin D levels decreased. CONCLUSIONS: our findings highlight a significant association between low serum vitamin D levels and CircS and its components, particularly with short sleep. This suggests a potentially pivotal role of vitamin D in the pathogenesis of Circadian syndrome.

Association of Physical Activity Patterns with the Metabolic Syndrome in Korean Adults: A Nationwide Cross-Sectional Study.

Background: Recent research has focused on a new group called the "weekend warriors". These individuals accumulate their recommended moderate to vigorous physical activity (MVPA) over just 1-2 days, often during weekends, while remaining relatively inactive during the rest of the week. However, the effects of engaging in low-frequency MVPA on the risk of metabolic syndrome (MetS) are not well understood. This study investigated the association between physical activity patterns and the risk of MetS among Korean adults. Methods: This study included 26,197 participants (11,804 male and 14,393 female) aged ≥ 20 years from the Korea National Health and Nutrition Examination Survey. MVPA was measured using a global physical activity questionnaire. MetS was defined as the presence of more than three risk factors. Results: The odds ratio (OR) for MetS was 0.60 (95% confidence interval [CI] = 0.52, 0.70) in the "regularly active" group and 0.82 (95% CI = 0.69, 0.98) in the "weekend warrior" group compared to that in the inactive group (reference), which controlled for all covariates. For sensitivity analyses, the results across all subgroups exhibited similar patterns, with more pronounced effects observed in women, middle-aged individuals, and non-drinkers/light drinkers. Conclusions: Our findings suggest that concentrated bouts of moderate to vigorous physical activity, even if undertaken infrequently, confer health benefits that align with the recommended guidelines. This study contributes to the growing evidence on the relationship between physical activity patterns and MetS risk in Korean adults. The study also emphasizes the potential of different activity patterns in mitigating metabolic risk.

Association between the metabolic score for insulin resistance and prostate cancer: a cross-sectional study in Xinjiang.

Background: Insulin resistance is associated with the development and progression of various cancers. However, the epidemiological evidence for the association between insulin resistance and prostate cancer is still limited. Objectives: To investigate the associations between insulin resistance and prostate cancer prevalence. Methods: A total of 451 patients who were pathologically diagnosed with prostate cancer in the First Affiliated Hospital of Xinjiang Medical University were selected as the case population; 1,863 participants who conducted physical examinations during the same period were selected as the control population. The metabolic score for insulin resistance (METS-IR) was calculated as a substitute indicator for evaluating insulin resistance. The Chi-square test and Mann-Whitney U test were performed to compare the basic information of the case population and control population. Univariate and multivariate logistic regression analyses to define factors that may influence prostate cancer prevalence. The generalized additive model (GAM) was applied to fit the relationship between METS-IR and prostate cancer. Interaction tests based on generalized additive model (GAM) and contour plots were also carried out to analyze the interaction effect of each factor with METS-IR on prostate cancer. Results: METS-IR as both a continuous and categorical variable suggested that METS-IR was negatively associated with prostate cancer prevalence. Smoothed curves fitted by generalized additive model (GAM) displayed a nonlinear correlation between METS-IR and prostate cancer prevalence (P < 0.001), and presented that METS-IR was negatively associated with the odds ratio (OR) of prostate cancer. The interaction based on the generalized additive model (GAM) revealed that METS-IR interacted with low-density lipoprotein cholesterol (LDL-c) to influence the prostate cancer prevalence (P = 0.004). Contour plots showed that the highest prevalence probability of prostate cancer was achieved when METS-IR was minimal and low-density lipoprotein cholesterol (LDL-c) or total cholesterol (TC) was maximal. Conclusions: METS-IR is nonlinearly and negatively associated with the prevalence of prostate cancer. The interaction between METS-IR and low-density lipoprotein cholesterol (LDL-c) has an impact on the prevalence of prostate cancer. The study suggests that the causal relationship between insulin resistance and prostate cancer still needs more research to confirm.

Off-iso Winston-Lutz test on seven linear accelerators.

PURPOSE: The aim of this study is to find optimal gantry, collimator, and couch angles for performing single isocenter, multiple target stereotactic radiosurgery (SIMT-SRS). Nineteen angle sets were tested across seven linear accelerators for radiation-isocenter coincidence and off-isocenter coincidence. The off-isocenter Winston-Lutz test was performed to evaluate the accuracy of isocenter alignment for each angle set, and optimal angle sets as well as maximum off-isocenter distance to target for each angle set was determined. The influence of simulated patient weight on off-iso Winston-Lutz test accuracy was also inspected. METHOD: The SNC MultiMet-WL phantom and MultiMet-WL QA Software v2.1 were used for the direct measurement and analysis of the off-iso Winston-Lutz test (also referred to as Winston-Lutz-Gao test). A two-step method was developed to ensure precise initial placement of the target. Nineteen beams were delivered at 6X energy and 2 × 2 cm field size to each of six targets on the MultiMet Cube with couch kicks at five cardinal angles (90°, 45°, 0°, 315°, and 270°). To reduce imaging uncertainty, only EPID was used in target alignment and test image acquisition. A total of 200 Ibs (90.7 kg) of weight was also used to mimic patient weight. All tests were performed on both the free table and the weighted table. RESULTS: For two new TrueBeam machines, the maximum offset was within the 1 mm tolerance when the off-iso distance is less than 7 cm. Two older VitalBeam machines exhibited unfavorable gantry, couch, and collimator (GCC) angle sets: Linac No. 3 at (0,90,0), (0,270,0) and Linac No. 4 at (0,45,45) and (0,90,0). The C-Series Linacs failed in the majority of GCC angle sets, with Linac No. 5 exhibiting a maximum offset of 1.53 mm. Four of seven machines show a clear trend that offset increases with off-isocenter distance. Additionally, the IGRT table was less susceptible to the addition of simulated patient weight than the ExactCouch. CONCLUSION: Among the seven linear accelerators addressed, newer model machines such as the Varian TrueBeam were more precise than older models, especially in comparison to the C-Series Linacs. The newer machines are more suitable for delivering SIMT-SRS procedures in all GCC angle sets, and the results indicate that newer TrueBeams are capable of performing SIMT-SRS procedures at all angle sets for targets of off-iso distances up to 7 cm. The trend that offset between the target center and radiation field center increases with off-iso distance, however, does not always hold true across machines. This may be comprised by the EPID's severe off-axis horn effect. Lastly, the IGRT couch was less susceptible to patient weight compared to ExactCouch in the off-isocenter Winston-Lutz test.

Effect of different optimization parameters in single isocenter multiple brain metastases radiosurgery.

PURPOSE: Automated treatment planning for multiple brain metastases differs from traditional planning approaches. It is therefore helpful to understand which parameters for optimization are available and how they affect the plan quality. This study aims to provide a reference for designing multi-metastases treatment plans and to define quality endpoints for benchmarking the technique from a scientific perspective. METHODS: In all, 20 patients with a total of 183 lesions were retrospectively planned according to four optimization scenarios. Plan quality was evaluated using common plan quality parameters such as conformity index, gradient index and dose to normal tissue. Therefore, different scenarios with combinations of optimization parameters were evaluated, while taking into account dependence on the number of treated lesions as well as influence of different beams. RESULTS: Different scenarios resulted in minor differences in plan quality. With increasing number of lesions, the number of monitor units increased, so did the dose to healthy tissue and the number of interlesional dose bridging in adjacent metastases. Highly modulated cases resulted in 4-10% higher V10% compared to less complex cases, while monitor units did not increase. Changing the energy to a flattening filter free (FFF) beam resulted in lower local V12Gy (whole brain-PTV) and even though the number of monitor units increased by 13-15%, on average 46% shorter treatment times were achieved. CONCLUSION: Although no clinically relevant differences in parameters where found, we identified some variation in the dose distributions of the different scenarios. Less complex scenarios generated visually more dose overlap; therefore, a more complex scenario may be preferred although differences in the quality metrics appear minor.

METS-IR/HOMA-IR and MAFLD in U.S. adults: dose-response correlation and the effect mediated by physical activity.

OBJECTIVES: Metabolic dysfunction-associated fatty liver disease (MAFLD), a globally prevalent disease, is closely linked to insulin resistance (IR). Physical activity (PA) is closely linked to both MAFLD and IR. We aim to explore the dose-response relationship between metabolic score for IR (METS-IR)/homeostasis model assessment of IR (HOMA-IR) and MAFLD, and investigate the relationship between PA, IR and MAFLD. METHODS: Participants from the NHANES study were included in this cross-section study. Logistic regression and the receiver operating characteristic were used to assess the predictive performance of METS-IR/HOMA-IR for MAFLD. Restrictive cubic splines were performed to visualize their dose-response relationship. Decision tree analysis was used to identify high-risk populations of MAFLD. PA's mediating effect in the association between METS-IR/HOMA-IR and MAFLD was also examined. RESULTS: Of all 1,313 participants, 693 had MAFLD (52.78%). There were a positive association between METS-IR (OR = 1.162, 95% CI = 1.126-1.199) and HOMA-IR (OR = 1.630, 95% CI = 1.431-1.856) and MAFLD risk. The AUCs of the METS-IR and HOMA-IR were 0.831 (0.809, 0.853) and 0.767 (0.741, 0.791), respectively, with significantly different predictive performance (P < 0.001). Adding METS-IR/HOMA-IR to the basic model greatly improved the statistical significance for MAFLD. Five high-risk subgroups were identified for MAFLD. PA mediated about 0.81% and 0.78% (indirect effect/total effect) in the association between METS-IR/HOMA-IR and MAFLD. CONCLUSIONS: MAFLD risk might be predicted by METS-IR/HOMA-IR, among which METS-IR performed better. And PA mediated the association between them. More attention should be paid to the therapeutic effect of lifestyle changes on MAFLD. HIGHLIGHTS: 1. Positive associations were found between METS-IR and HOMA-IR and MAFLD risk. 2. METS-IR has better predictive performance for MAFLD risk than HOMA-IR. 3.Two high-risk subgroups were identified for MAFLD by METS-IR: individuals with METS-IR ≥ 40; Hispanic black individuals with 34 ≤ METS-IR < 40 and aged ≥ 46. 4. In the significant association between METS-IR/HOMA-IR and MAFLD, about 0.81% and 0.78% (indirect effect/total effect), respectively, were mediated by physical activity.

Relationship between four insulin resistance surrogates and regression to normoglycemia from prediabetes among Chinese adults: A longitudinal Cohort Study.

PURPOSE: We aimed to investigate the association of the triglyceride glucose-body mass index(TyG-BMI), metabolic score for insulin resistance (METS-IR) with regression to normoglycaemia, and further to compare the value of the four insulin resistance(IR) related indices(TyG-BMI, METS-IR, TyG and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio) in identifying regressions to normoglycaemia from prediabetes. METHODS: A total of 15,025 patients with prediabetes from the DATA-DRYAD database were included. Cox proportional hazards regression models and restricted cubic spline functions were performed to explore the association and nonlinearity between the indices with the incidence rate of normoglycaemia. Sensitivity and subgroup analyses evaluated the robustness of our findings. RESULTS: Compared with the first quintile, TyG-BMI and METS-IR was negatively linked with the probability of regression to normoglycaemia from prediabetes, the adjusted effect size of the highest quintiles of METS-IR were the most obvious (HR:0.456,95% CI:0.4-0.519), followed by TG/HDL (HR:0.792, 95% CI:0.733-0.856), TyG-BMI (HR:0.816, 95% CI:0.73-0.911) and TyG (HR:0.841, 95% CI: 0.754-0.937) (all p for trend <0.001). A 1.0 SD increase in METS-IR induced a 43% decrease in the probability of regression to normoglycaemia, with 9.8% for TyG-BMI. There were nonlinear associations between TyG-BMI and METS-IR and outcomes, with the inflection point of the TyG-BMI being 218.2 and that of the METS-IR being 37. CONCLUSIONS: The METS-IR might be the most superior indicator among the four non-insulin indices in identifying regressions to normoglycaemia from prediabetes in clinical application. The inflection points of the METS-IR and TyG-BMI may be instructive therapeutic points for assessing the status of prediabetes in advance and making more appropriate management and health care decisions.

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome.

Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS: We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.

Association between anti-mullerian hormone and metabolic syndrome: insights from a prospective community-based study.

BACKGROUND: Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed to examine the relationship between AMH levels and MetS and its components in women from a general population. METHODS: This prospective study recruited 769 women. Generalized Estimating Equation (GEE) models analyzed longitudinal trends of MetS components. Cox proportional hazard models evaluated effect of age-specific AMH tertiles on MetS occurrence, adjusting for confounders. RESULTS: The GEE analysis indicated that women in the third tertile exhibited higher mean FPG compared to those in the first tertile of age-specific AMH (3 mg/dL; 95% CI: 0.40, 5.60; P = 0.024); however, this association became non-significant after adjustment. Notably, the second tertile showed a significant decrease in FPG mean changes over time (-0.69 mg/dL; 95% CI: -1.31, -0.07; P Interaction = 0.030). Women in the second and third tertiles of age-specific AMH demonstrated lower mean HDL-C compared to the first tertile (-2.96 mg/dL; 95% CI: -4.67, -1.26; P < 0.001 and -2.63 mg/dL; 95% CI: -4.31, -0.96; P = 0.002, respectively). The association between HDL-C changes and the second tertile remained significant after adjustment (-1.91 mg/dL; 95% CI: -3.68, -0.14; P = 0.034). No significant associations were observed between age-specific AMH tertiles and TG and SBP/DBP. Cox models revealed no significant differences in the hazard ratio of MetS between AMH tertiles after adjusting for confounders. CONCLUSION: Despite minor variations in MetS components, AMH levels did not affect MetS risk in women from a general population.

Systems genetics of metabolic health in the BXD mouse genetic reference population.

Susceptibility to metabolic syndrome (MetS) is dependent on genetics, environment, and gene-by-environment interactions, rendering the study of underlying mechanisms challenging. The majority of experiments in model organisms do not incorporate genetic variation and lack specific evaluation criteria for MetS. Here, we derived a continuous metric, the metabolic health score (MHS), based on standard clinical parameters and defined its molecular signatures in the liver and circulation. In human UK Biobank, the MHS associated with MetS status and was predictive of future disease incidence, even in individuals without MetS. Using quantitative trait locus analyses in mice, we found two MHS-associated genetic loci and replicated them in unrelated mouse populations. Through a prioritization scheme in mice and human genetic data, we identified TNKS and MCPH1 as candidates mediating differences in the MHS. Our findings provide insights into the molecular mechanisms sustaining metabolic health across species and uncover likely regulators. A record of this paper's transparent peer review process is included in the supplemental information.