Urine organic acids may be useful biomarkers for metabolic syndrome and its components in Korean adults.

OBJECTIVES: Although metabolic syndrome (MetS) and its components are defined clinically, those with MetS may have various derangements in metabolic pathways. Thus, this study aimed to evaluate the traits of urine organic acid metabolites indicating the metabolic intermediates of the pathways in the subjects with MetS. METHODS: This cross-sectional study included 246 men and 283 women in a hospital health check-up setting. Urine organic acid metabolites were assayed via high-performance liquid chromatography-mass spectrometry analyses. A high level of each metabolite was defined as the fifth quintile of the distribution. RESULTS: The subjects with MetS had high levels of pyruvate, α-ketoglutarate, α-ketoisovalerate, α-ketoisocaproate, formiminoglutamate, and quinolinate (odds ratios from 1.915 to 2.809 in logistic models adjusted for age and sex). Among the metabolites, pyruvate, formiminoglutamate, and quinolinate were not independent of homeostatic model assessment of insulin resistance (HOMA2-IR). Several metabolites were associated with one or more components of MetS and HOMA2-IR. CONCLUSIONS: Urine organic acid metabolites in MetS are characterized in altered carbohydrate and amino acid metabolism. MetS shared some traits in insulin resistance. These findings may promote the understanding of the pathophysiology of MetS.

A cross-sectional study of the association between adipokine levels and bone mineral density according to obesity and menopausal status in Korean women.

Results regarding the association between adipokine levels and bone mineral density (BMD) have been inconsistent; the effects of sex, menopause, and central obesity remain unknown. We evaluated the association between serum leptin, adiponectin, and high-molecular-weight (HMW) adiponectin levels and BMD according to menopause and central obesity status in Korean women. This cross-sectional study comprised 255 women undergoing examinations at the CHA Bundang Medical Center. Participants were divided according to menopause, and central obesity status. We measured serum adipokine levels and BMD using an enzyme-linked immunosorbent assay and dual-energy X-ray absorptiometry, respectively. After adjusting for age, body mass index, alkaline phosphatase levels and the Homeostasis Model Assessment index, leptin levels were negatively associated with non-vertebral BMD (total hip, ß = -0.576, P = 0.006; femoral neck, ß = -0.608, P = 0.007) in postmenopausal women without central obesity. Among women without central obesity, HMW adiponectin levels were positively associated with total hip BMD (ß = 0.240, P = 0.010) in premenopausal women but negatively associated with BMD (lumbar, ß = -0.436, P = 0.012; femoral neck, ß = -0.468, P = 0.007) in postmenopausal women. Thus, the association between adipokine levels and BMD varies according to the menopause and central obesity status.

The association of testosterone, sex hormone-binding globulin, and insulin-like growth factor-1 with bone parameters in Korean men aged 50 years or older.

Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for the maintenance of bone health in men. However, the results for the association of testosterone and IGF-1 with bone parameters were not consistent in prior studies. We evaluated the relationship of testosterone, sex hormone-binding globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover markers (BTMs) in Korean men. We enrolled 1227 men aged ≥50 years in this cross-sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX) were measured. Free testosterone (FT) was calculated using Vermeulen's method. BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1, the association between TT and BTMs was significant (ß = -0.139 for osteocalcin and ß = -0.204 for CTX). SHBG levels were negatively associated with lumbar BMD, and positively associated with BTMs in all models. As SHBG level increased, the prevalence of osteopenia or osteoporosis defined by BMD significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly related with BMD, but not with BTMs. Meanwhile, FT levels were positively associated with BMD and negatively associated with BTMs. In conclusion, SHBG levels were independently related with bone parameters and osteopenia in men aged ≥50 years. IGF-1 levels were positively associated with BMD, but not with BTMs. SHBG may play a role in regulating age-related bone loss in men after middle-age.

Association of serum 25-hydroxyvitamin D and serum total cholesterol with depressive symptoms in Korean adults: the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012).

OBJECTIVE: To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population. DESIGN: This was a population-based cross-sectional study. SETTING: The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). SUBJECTS: We included 7198 adults aged 20-88 years. RESULTS: The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles). CONCLUSIONS: The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.

Prediction of prevalent but not incident non-alcoholic fatty liver disease by levels of serum testosterone.

BACKGROUND AND AIMS: The association between testosterone level and development of non-alcoholic fatty liver disease (NAFLD) is not well known. We examined the relationship of total testosterone level with development and regression of NAFLD. METHODS: Among the men who had undergone repeated liver ultrasonography in 2 years or more at a health promotion center, subjects with available serum testosterone level at baseline were included in the study. Alcohol consumers (> 20 g/day) were excluded from the study. RESULTS: Among the 1944 men, 44.3% of subjects were diagnosed with NAFLD. Higher level of testosterone significantly lowered the prevalence of fatty liver (odds ratios per SD increase, 0.686 and 0.795 at baseline and follow-up, respectively). During the median 4.2 years follow-up, 22.4% of subjects in the normal group developed fatty liver, and 21.0% of subjects in the NAFLD group recovered at the follow-up. In longitudinal analyses, higher level of testosterone was significantly associated with the development or regression of fatty liver, before adjustment for obesity and metabolic parameters. However, in the full-adjusted model, testosterone level did not influence the development or regression of fatty liver. CONCLUSIONS: Although testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses, baseline testosterone level did not independently influence the development or regression of fatty liver at the median 4.2 years follow-up. Obesity and metabolic parameters may play key roles in the link between testosterone level and NAFLD.

Application of Machine Learning Algorithms to Predict Osteoporotic Fractures in Women.

BACKGROUND: Predicting the risk of osteoporotic fractures is vital for prevention. Traditional methods such as the Fracture Risk Assessment Tool (FRAX) model use clinical factors. This study examined the predictive power of the FRAX score and machine-learning algorithms trained on FRAX parameters. METHODS: We analyzed the data of 2,147 female participants from the Ansan cohort study. The FRAX parameters employed in this study included age, sex (female), height and weight, current smoking status, excessive alcohol consumption (>3 units/d of alcohol), and diagnosis of rheumatoid arthritis. Osteoporotic fracture was defined as one or more fractures of the hip, spine, or wrist during a 10-year observation period. Machine-learning algorithms, such as gradient boosting, random forest, decision tree, and logistic regression, were employed to predict osteoporotic fractures with a 70:30 training-to-test set ratio. We evaluated the area under the receiver operating characteristic curve (AUROC) scores to assess and compare the performance of these algorithms with the FRAX score. RESULTS: Of the 2,147 participants, 3.5% experienced osteoporotic fractures. Those with fractures were older, shorter in height, and had a higher prevalence of rheumatoid arthritis, as well as higher FRAX scores. The AUROC for the FRAX was 0.617. The machine-learning algorithms showed AUROC values of 0.662, 0.652, 0.648, and 0.637 for gradient boosting, logistic regression, decision tree, and random forest, respectively. CONCLUSION: This study highlighted the immense potential of machine-learning algorithms to improve osteoporotic fracture risk prediction in women when complete FRAX parameter information is unavailable.

Decreased natural killer cell activity as a potential predictor of hypertensive incidence.

Introduction: Blood pressure is closely linked with immune function. This study examined the association between natural killer (NK) cell activity (NKA) and blood pressure and the development of hypertension according to NKA levels. Methods: This study enrolled 1543 adults who underwent NKA measurement and serial health check-ups at a medical center in Korea. NKA was estimated as the concentration of IFN-γ in the incubated whole blood containing a patented stimulatory cytokine. The participants were categorized into quartiles according to their NKA levels. Participants without hypertension were followed up, and the development of hypertension was compared according to the quartiles. Results: The prevalence of hypertension was not different among the NKA quartiles, whereas blood pressures significantly decreased, followed by an increment of quartiles (systolic blood pressure of 119.0 in Q1 and 117.0 in Q4, P-trend = 0.018). Over a mean follow-up period of 2.13 years, hypertension developed in 156 of 1170 individuals without baseline hypertension. The hazard ratio of Q4 compared with Q1 was 0.625 (95% CI: 0.397-0.983; p = 0.042). Conclusion: In conclusion, our findings indicate a correlation between lower NKA and higher blood pressure and the development of incident hypertension. This may suggest a potential protective role of NK cells against endothelial dysfunction. Further research is necessary to elucidate the specific relationship between immune functions and endothelial function.

Preventive machine learning models incorporating health checkup data and hair mineral analysis for low bone mass identification.

Machine learning (ML) models have been increasingly employed to predict osteoporosis. However, the incorporation of hair minerals into ML models remains unexplored. This study aimed to develop ML models for predicting low bone mass (LBM) using health checkup data and hair mineral analysis. A total of 1206 postmenopausal women and 820 men aged 50 years or older at a health promotion center were included in this study. LBM was defined as a T-score below - 1 at the lumbar, femur neck, or total hip area. The proportion of individuals with LBM was 59.4% (n = 1205). The features used in the models comprised 50 health checkup items and 22 hair minerals. The ML algorithms employed were Extreme Gradient Boosting (XGB), Random Forest (RF), Gradient Boosting (GB), and Adaptive Boosting (AdaBoost). The subjects were divided into training and test datasets with an 80:20 ratio. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and an F1 score were evaluated to measure the performances of the models. Through 50 repetitions, the mean (standard deviation) AUROC for LBM was 0.744 (± 0.021) for XGB, the highest among the models, followed by 0.737 (± 0.023) for AdaBoost, and 0.733 (± 0.023) for GB, and 0.732 (± 0.021) for RF. The XGB model had an accuracy of 68.7%, sensitivity of 80.7%, specificity of 51.1%, PPV of 70.9%, NPV of 64.3%, and an F1 score of 0.754. However, these performance metrics did not demonstrate notable differences among the models. The XGB model identified sulfur, sodium, mercury, copper, magnesium, arsenic, and phosphate as crucial hair mineral features. The study findings emphasize the significance of employing ML algorithms for predicting LBM. Integrating health checkup data and hair mineral analysis into these models may provide valuable insights into identifying individuals at risk of LBM.

Obesity in Children and Adolescents: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity in children and adolescents has been gradually increasing in recent years and has become a major health problem. Childhood obesity can readily progress to adult obesity. It is associated with obesity-related comorbidities, such as type 2 diabetes mellitus, hypertension, obstructive sleep apnea, non-alcoholic fatty liver disease, and the risk factor for cardiovascular disease. It is important to make an accurate assessment of overweight and obesity in children and adolescents with consideration of growth and development. Childhood obesity can then be prevented and treated using an appropriate treatment goal and safe and effective treatment strategies. This article summarizes the clinical practice guidelines for obesity in children and adolescents that are included in the 8th edition of the Clinical Practice Guidelines for Obesity of the Korean Society for the Study of Obesity.

Relationship between Serum Cortisol, Dehydroepiandrosterone Sulfate (DHEAS) Levels, and Natural Killer Cell Activity: A Cross-Sectional Study.

The adrenal steroid hormones, cortisol and dehydroepiandrosterone sulfate (DHEAS), are associated with the immune system in opposite actions. This study aimed to investigate the relationship between cortisol and DHEAS serum concentrations, their ratio (CDR), and natural killer cell activity (NKA). This cross-sectional study included 2275 subjects without current infection or inflammation in the final analyses. NKA was estimated by measuring the amount of interferon-gamma (IFN-γ) released by activated natural killer cells; low NKA was defined as IFN-γ level < 500 pg/mL. Cortisol, DHEAS levels, and CDRs were categorized by quartiles in men, premenopausal women, and postmenopausal women. Compared with the lowest quartile as reference, the adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for low NKA of the highest cortisol and CDR group were 1.66 (1.09-2.51) and 1.68 (1.11-2.55) in men, 1.58 (1.07-2.33) and 2.33 (1.58-3.46) in premenopausal women, and 2.23 (1.28-3.87) and 1.85 (1.07-3.21) in postmenopausal women. Only in premenopausal women, the highest DHEAS group showed significantly lower risk of low NKA (OR: 0.51, 95% CI: 0.35-0.76). HPA axis activation indicated as high cortisol level, CDR was significantly associated with low NKA, while high DHEAS levels were inversely associated with low NKA in premenopausal women.

Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m2 and obesity as a BMI ≥25 kg/m2, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Diagnosis of Obesity: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The prevalence of obesity has consistently increased worldwide, and many obesity-related diseases are emerging as major health problems. Body mass index (BMI) is used to define obesity and is highly correlated with body fat mass. Moreover, obesity-related morbidities increase linearly with the increase in BMI. The Korean Society for the Study of Obesity defined overweight as a BMI ≥23 kg/m2 and obesity as a BMI ≥25 kg/m2, based on a significant increase in obesity-related diseases. A waist circumference of ≥90 cm in men and ≥85 cm in women are defined as abdominal obesity, which is also correlated with obesity-related diseases. These diagnostic criteria are the same as in the previous version; however, the updated guidelines put greater emphasis on the use of morbidity as the basis for obesity and abdominal obesity diagnoses. These new guidelines will help to identify and manage high-risk groups for obesity-related comorbidities among Korean adults.

Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

Characteristics of Urine Organic Acid Metabolites in Nonalcoholic Fatty Liver Disease Assessed Using Magnetic Resonance Imaging with Elastography in Korean Adults.

The liver is an essential organ that manufactures energy through various metabolic pathways; thus, exploring the intermediate metabolites in nonalcoholic fatty liver disease (NAFLD) may help discover novel parameters in hepatic steatosis or fibrosis. The present study aimed to investigate the traits of urine organic acid metabolites in participants with hepatic steatosis and fibrosis in nonalcoholic Korean adults. Hepatic steatosis and fibrosis, in 68 men and 65 women, were evaluated using quantification by proton density fat fraction with magnetic resonance (MR) imaging and MR elastography, respectively. Urine metabolites were obtained using a high-performance liquid chromatography-mass spectrometry analysis. The candidate metabolites were included in the logistic regression models for hepatic steatosis and fibrosis. The association between high p-hydroxyphenyllactate levels and hepatic steatosis was not independent of body mass index and Homeostatic Model Assessment-insulin resistance. High ethylmalonate, ß-hydroxybutyrate, and sulfate levels were significantly related to a low probability of hepatic fibrosis, independent of covariates. In conclusion, urine metabolites were not related to hepatic steatosis independent of obesity and insulin resistance, while several metabolites were specifically associated with hepatic fibrosis. Further study is required to verify the diagnostic value of the metabolites in a population with wide-spectrum NAFLD.

A Case-Control Study on the Changes in Natural Killer Cell Activity following Administration of Polyvalent Mechanical Bacterial Lysate in Korean Adults with Recurrent Respiratory Tract Infection.

Polyvalent mechanical bacterial lysate (PMBL) is used for the treatment and prevention of recurrent respiratory tract infections. Although PMBL is an immunostimulant, it remains unknown whether treatment with PMBL influences natural killer cell activity (NKA). Hence, this case-control study compared the changes in IFN-γ levels (surrogate index for NKA) following PMBL treatment or time passing between the PMBL-treated group and controls. The treatment group included adults who had a PMBL prescription for three months against recurrent respiratory tract infection from an outpatient clinic, while the control group had healthy adults visiting the health promotion center for periodic health check-ups. The control group (N = 506) showed no change in IFN-γ levels, while the treatment group (N = 301) showed a significant increase in mean from 462.8 to 749.3 pg/mL after PMBL treatment. In the subgroup with IFN-γ <500 pg/mL, IFN-γ levels significantly increased in both groups. However, the change in the treatment group (287 ± 822 pg/mL) was greater than that in the control group (58 ± 809 pg/mL), and the interaction between the visit and case/control was significant (p = 0.030) in a generalized estimating equation model. In conclusion, NKA increased in the subjects with recurrent respiratory tract infections with PMBL treatment.

Cross-Sectional and Time-Dependent Analyses on Inflammatory Markers following Natural Killer Cell Activity.

The function of natural killer (NK) cells in inflammation has not been explored enough in large-scale population studies. The cross-sectional and time-dependent relationship between NK cell activity (NKA) and inflammatory markers was examined. METHODS: A total of 7031 subjects were involved in the cross-sectional analyses. Non-linear relationship between NKA and inflammatory indices was analyzed using generalized additive models. The time-dependent changes were analyzed in 1005 subjects with repeated measurement in 3-6 months. The changes in inflammatory markers were analyzed based on the changes in NKA. RESULTS: As NKA reduces to a very low level, the white blood cell (WBC) and neutrophil counts increase sharply, and the lymphocyte count exhibits a slow decline. With increasing NKA larger than about 500 pg/mL, WBC and neutrophil-lymphocyte ratio (NLR) reduces in a mild slope. Among the subjects with repeated measurements, the follow-up NKA was increased with advancing baseline NKA levels. The subjects with a reduction in NKA indicated increment in WBC count, neutrophil count, and NLR, and decrease in lymphocyte count. CONCLUSIONS: Very low levels of NKA suggest a high inflammatory immune response. The changes in NKA may interact with the balance between neutrophils and lymphocytes.

Fatty Liver Change in Korean Adults in a Systematic Social Distancing System Amid the COVID-19 Pandemic: A Multicenter Analysis.

In response to the COVID-19 pandemic, the Korean government implemented policies including the systematic social distancing (SSD) system which started on 28 June 2020. The present study investigated the development and aggravation of fatty liver measured using ultrasonography during the transition period (from pre-SSD to SSD) compared to the fatty liver changes during the pre-SSD period. Changes in fatty liver and liver enzymes were assessed in different groups stratified by alcohol consumption. Our retrospective cohort analysis included 5668 participants who underwent health checkups at 13 university hospitals during the SSD period and two or more checkups before the SSD period. Fatty liver developed and aggravated more in the transition period (13.6% development and 12.0% aggravation) than in the pre-SSD period (10.8% development and 10.1% aggravation) in the alcohol consumption group. This finding was more prominent in women than in men. Abnormal alanine transaminase levels were more often developed in the transition period than in the pre-SSD period, especially in men (11.1% vs. 8.6% in each period). In conclusion, the SSD system may contribute to fatty liver changes in individuals who regularly consume alcohol. Further research of the post-pandemic period is needed to assess long-term changes in fatty liver disease.

COVID-19 and related social distancing measures induce significant metabolic complications without prominent weight gain in Korean adults.

Background: This study using multi-center health examination data from Korean adults was conducted to confirm changes in weight, and their related cardiometabolic parameters, before and after strengthening of social distancing regulations. Methods: A retrospective cohort study was conducted using health check-up data from 13 university hospitals. The study period was from January 2018 to July 2020. To examine the effect of systematic social distancing measures, participants who underwent a health check-up (Visit 3) between July 2020 and July 2021 (during full scale social distancing), and had undergone two previous health check-ups (Visits 1 and 2) between January 2018 and June 2020 (before social distancing), were selected. In total, data from 7,875 participants were analyzed. Linear mixed-effect models were used to calculate estimates of anthropometric indices and metabolic markers measured on Visits 2 and 3, compared with measurements from Visit 1. Results: There were no significant differences in body weight, body mass index, waist circumference, and body composition on Visit 3 than on Visits 1 and 2. However, the odds of metabolic syndrome and its components, including hypertension, high glucose, diabetes, hypercholesterolemia, hypertriglyceridemia, hyper-non-high-density lipoprotein cholesterolemia, and dyslipidemia were significantly higher on Visit 3 than on Visits 1 and 2. The increase in metabolic complications was marked, particularly in relatively young adults who visited health check-up centers located in the capital area. Conclusion: Metabolic syndrome and its components were significantly worse after high level social distancing, although there were no significant increases in anthropometric indices and body fat levels. Healthcare providers need to prevent and manage worsening of metabolic parameters in subpopulations prone to be more sedentary and eat unhealthy food during the COVID-19 pandemic and associated social distancing measures.

Elevated levels of urine isocitrate, hydroxymethylglutarate, and formiminoglutamate are associated with arterial stiffness in Korean adults.

Recent evidence suggests that cellular perturbations play an important role in the pathogenesis of cardiovascular diseases. Therefore, we analyzed the association between the levels of urinary metabolites and arterial stiffness. Our cross-sectional study included 330 Korean men and women. The brachial-ankle pulse wave velocity was measured as a marker of arterial stiffness. Urinary metabolites were evaluated using a high-performance liquid chromatograph-mass spectrometer. The brachial-ankle pulse wave velocity was found to be positively correlated with L-lactate, citrate, isocitrate, succinate, malate, hydroxymethylglutarate, α-ketoisovalerate, α-keto-ß-methylvalerate, methylmalonate, and formiminoglutamate among men. Whereas, among women, the brachial-ankle pulse wave velocity was positively correlated with cis-aconitate, isocitrate, hydroxymethylglutarate, and formiminoglutamate. In the multivariable regression models adjusted for conventional cardiovascular risk factors, three metabolite concentrations (urine isocitrate, hydroxymethylglutarate, and formiminoglutamate) were independently and positively associated with brachial-ankle pulse wave velocity. Increased urine isocitrate, hydroxymethylglutarate, and formiminoglutamate concentrations were associated with brachial-ankle pulse wave velocity and independent of conventional cardiovascular risk factors. Our findings suggest that metabolic disturbances in cells may be related to arterial stiffness.

Low levels of total and high-molecular-weight adiponectin may predict non-alcoholic fatty liver in Korean adults.

OBJECTIVES: While weight gain is known as a predictor of non-alcoholic fatty liver disease (NAFLD) incidence, it remains controversial whether adipokine levels predict the development of NAFLD. We aimed to investigate the relationship of total adiponectin, high-molecular-weight (HMW) adiponectin, and leptin with the development and improvement of non-alcoholic fatty liver (NAFL) independent of sex and weight change over a maximum of 8.5 years. METHODS: This prospective study enrolled 2735 participants in a hospital health check-up setting. Adipokine levels were measured at baseline. NAFL was assessed with liver ultrasonography, and the development or improvement of NAFL was determined by repeated ultrasonography at follow-ups. RESULTS: Cross-sectional analyses revealed that total and HMW adiponectin levels were inversely associated with NAFL prevalence. In longitudinal analyses, the incidence of NAFL was 5.6 per 100-person-years during the observation period. The hazard ratios (HRs) per 1 µg/mL increase in the levels of total and HMW adiponectin were 0.900 (0.836-0.969) and 0.846 (0.754-0.948), respectively. Sex-stratified analyses showed that total and HMW adiponectin levels were significantly related to NAFL incidence only in women. In the subgroup of minimal weight change, only HMW adiponectin was a significant predictor for NAFL. Leptin predicted NAFL in the subgroup with weight gain. The improvement of NAFL was influenced by weight change, but not by adipokine levels. CONCLUSIONS: Low levels of total and HMW adiponectin may predict the development of NAFL independent of pathophysiological factors including obesity and insulin resistance. This predictability was evident in women. Leptin was a significant predictor for NAFL in the subjects with weight gain.