Handgrip strength thresholds associated with metabolic syndrome risk in children and adolescents: a systematic review and meta-analysis.

Objectives: Certain studies have reported that handgrip strength (HGS) is associated with metabolic health risks in children and adolescents, and some studies have suggested HGS thresholds for identifying poor metabolic health. Therefore, we aimed to determine the HGS thresholds associated with metabolic syndrome (MetS) in children and adolescents through a systematic review. Methods: We searched 3 electronic databases from their inception until October 2023 to identify original papers that focused on children and adolescents and assessed their risks of MetS according to specific HGS values. Studies were selected for inclusion through a planned screening process based on specific criteria. The Quality Assessment Tool for Diagnostic Accuracy Studies v2 (QUADAS-2) was used to evaluate quality, and a meta-analysis was performed using the diagmeta R package to suggest the optimal thresholds. Results: From the search, 8 studies were selected for this systematic review. For detecting MetS risk, the optimal threshold for HGS (defined as relative HGS by adjusting for body mass) was found to be 0.422, with a sensitivity of 76.7% (95% confidence interval [CI], 64.0% to 85.8%) and a specificity of 62.9% (95% CI, 56.9% to 68.5%). The stratification analysis by sex resulted in optimal thresholds of 0.416 for boys and 0.376 for girls. Additionally, when the data were stratified by age, the thresholds were 0.356 for children and 0.416 for adolescents. Conclusion: : Our results provide practical information for detecting high-risk groups and encouraging strength-related activities that may reduce the risk of MetS in children and adolescents.

Association between Thyroid Function and Insulin Resistance Indices in Korean Adolescents: Findings from the 2014-2015 Korea National Health and Nutrition Examination Survey.

AIM: This study investigated the sex-specific association between thyroid function and various insulin resistance (IR) indices, including noninsulin-based IR indices, in euthyroid adolescents. METHODS: A total of 465 adolescents (aged 12-18 years; 255 boys and 210 girls) based on data from the 2014-2015 Korea National Health and Nutrition Examination Survey were included. Serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (fT4) were used to assess thyroid function, whereas the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), glucose/insulin ratio (GIR), triglyceride-glucose (TyG) index, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to assess IR. The relationship between thyroid function and IR was analyzed using multiple linear regressions stratified by sex, considering obesity status. RESULTS: The relationship between thyroid function and IR varied depending on sex and was more pronounced in the overweight/obesity subgroup for both boys and girls. In overweight and obese boys and girls, fT4 was significantly associated with HOMA-IR and QUICKI with conflicting association directions. TSH was also positively associated with the TyG index in both sexes. CONCLUSIONS: The findings suggest that the relationship between thyroid function and IR in adolescents might vary depending on sex, and the degree of association was significant in obese adolescents.

Validation of the Framingham Diabetes Risk Model Using Community-Based KoGES Data.

BACKGROUND: An 8-year prediction of the Framingham Diabetes Risk Model (FDRM) was proposed, but the predictor has a gap with current clinical standards. Therefore, we evaluated the validity of the original FDRM in Korean population data, developed a modified FDRM by redefining the predictors based on current knowledge, and evaluated the internal and external validity. METHODS: Using data from a community-based cohort in Korea (n = 5,409), we calculated the probability of diabetes through FDRM, and developed a modified FDRM based on modified definitions of hypertension (HTN) and diabetes. We also added clinical features related to diabetes to the predictive model. Model performance was evaluated and compared by area under the curve (AUC). RESULTS: During the 8-year follow-up, the cumulative incidence of diabetes was 8.5%. The modified FDRM consisted of age, obesity, HTN, hypo-high-density lipoprotein cholesterol, elevated triglyceride, fasting glucose, and hemoglobin A1c. The expanded clinical model added γ-glutamyl transpeptidase to the modified FDRM. The FDRM showed an estimated AUC of 0.71, and the model's performance improved to an AUC of 0.82 after applying the redefined predictor. Adding clinical features (AUC = 0.83) to the modified FDRM further improved in discrimination, but this was not maintained in the validation data set. External validation was evaluated on population-based cohort data and both modified models performed well, with AUC above 0.82. CONCLUSION: The performance of FDRM in the Korean population was found to be acceptable for predicting diabetes, but it was improved when corrected with redefined predictors. The validity of the modified model needs to be further evaluated.

Differences in coronary angiographic findings and outcomes between men and postmenopausal women with stable chest pain.

BACKGROUND: Despite the significant increase in cardiovascular events in women after menopause, studies comparing postmenopausal women and men are scarce. METHODS: We analyzed data from a nationwide, multicenter, prospective registry and enrolled 2412 patients with stable chest pain who underwent elective coronary angiography. Binary coronary artery disease (b-CAD) was defined as the ≥50% stenosis of epicardial coronary arteries, including the left main coronary artery. RESULTS: Compared with the men, postmenopausal women were older (66.6 ±â€…8.5 vs. 59.5 ±â€…11.4 years) and had higher high-density lipoprotein cholesterol levels (49.0 ±â€…12.8 vs. 43.6 ±â€…11.6 mg/dl, P  < 0.01). The prevalence of diabetes did not differ significantly ( P  = 0.40), and smoking was more common in men than in postmenopausal women ( P  ≤ 0.01). At enrollment, b-CAD and revascularization were more common in men than in postmenopausal women (50.3% vs. 41.0% and 14.4% vs. 9.7%, respectively; both P  < 0.01). However, multivariate analyses revealed that revascularization [odds ratio (OR): 0.72; 95% confidence interval (CI): 0.49-1.08] was not significantly related to sex and a similar result was found in age propensity-matched population (OR: 0.80; 95% CI: 0.52-1.24). During the follow-up period, the secondary composite cardiovascular outcomes were lower in postmenopausal women than in men (OR: 0.55; 95% CI: 0.31-0.98), also consistent with the result using the age propensity-mated population (OR: 0.33; 95% CI: 0.13-0.85). CONCLUSION: Postmenopausal women experienced coronary revascularization comparable to those in men at enrollment, despite the average age of postmenopausal women was 7 years older than that of men.Postmenopausal women exhibit better clinical outcomes than those of men if optimal treatment is provided.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Metabolically healthy obese individuals are still at high risk for diabetes: Application of the marginal structural model.

AIM: To assess the effect of obesity phenotype on the incidence of diabetes, considering phenotype as a time-varying exposure. METHODS: We used community-based cohort data from the Korean Genome and Epidemiology Study, with a 16-year follow-up period. Obesity phenotype was determined using body mass index and metabolic syndrome criteria. The influence of obesity phenotype on the occurrence of diabetes was evaluated using a Cox proportional hazard model and a marginal structural model (MSM). RESULTS: Obesity phenotypes were defined in 6265 individuals, with diabetes identified in 903 (14.4%) during the follow-up period. Individuals with metabolically healthy obesity (MHO) exhibited a higher risk of diabetes compared to those with metabolically healthy normal weight (MHNW), with a hazard ratio (HR) of 1.48 (95% confidence interval [CI] 1.15-1.90). This association remained significant after applying the MSM (HR 1.49, 95% CI 1.01-2.20). Moreover, various sensitivity analyses consistently demonstrated a higher risk of diabetes in individuals with MHO compared to those with MHNW. CONCLUSIONS: Even when obesity phenotype was treated as a time-varying exposure, individuals with MHO were still at higher risk for developing diabetes than those with MHNW. Consequently, such individuals should aim to avoid transitioning to a metabolically unfavourable state and strive to reduce their body weight to a normal range.

A network-based approach to explore comorbidity patterns among community-dwelling older adults living alone.

The detailed comorbidity patterns of community-dwelling older adults have not yet been explored. This study employed a network-based approach to investigate the comorbidity patterns of community-dwelling older adults living alone. The sample comprised a cross-sectional cohort of adults 65 or older living alone in a Korean city (n = 1041; mean age = 77.7 years, 77.6% women). A comorbidity network analysis that estimates networks aggregated from measures of significant co-occurrence between pairs of diseases was employed to investigate comorbid associations between 31 chronic conditions. A cluster detection algorithm was employed to identify specific clusters of comorbidities. The association strength was expressed as the observed-to-expected ratio (OER). As a result, fifteen diseases were interconnected within the network (OER > 1, p-value < .05). While hypertension had a high prevalence, osteoporosis was the most central disease, co-occurring with numerous other diseases. The strongest associations among comorbidities were found between thyroid disease and urinary incontinence, chronic otitis media and osteoporosis, gastric duodenal ulcer/gastritis and anemia, and depression and gastric duodenal ulcer/gastritis (OER > 1.85). Three distinct clusters were identified as follows: (a) cataracts, osteoporosis, chronic otitis media, osteoarthritis/rheumatism, low back pain/sciatica, urinary incontinence, post-accident sequelae, and thyroid diseases; (b) hyperlipidemia, diabetes mellitus, and hypertension; and (c) depression, skin disease, gastric duodenal ulcer/gastritis, and anemia. The results may prove valuable in guiding the early diagnosis, management, and treatment of comorbidities in older adults living alone.

Genetic predisposition, lifestyle inflammation score, food-based dietary inflammatory index, and the risk for incident diabetes: Findings from the KoGES data.

BACKGROUND AND AIMS: We investigated whether genetic predisposition, the Lifestyle Inflammation Score (LIS), or the Food-based Dietary Inflammatory Index (FDII) were associated with diabetes incidence and whether these factors interact. METHODS AND RESULTS: The study was conducted using population-based cohort data derived from the Korean Genome and Epidemiology Study, which included 6568 people aged 40-69 years. Based on 25 genetic variants related to diabetes, genetic risk scores (GRSs) were determined and LISs and FDIIs were calculated and stratified into quartiles. We investigated the effects of gene-lifestyle interactions on the incident diabetes. The multivariate Cox proportional hazard model was used to generate hazard ratios with 95 % CIs. During the 16-year follow-up period, diabetes incidence was 13.6 per 1000 person-years. A dose-response association with diabetes was observed for both GRS and LIS quartiles but not for FDII quartiles. The GRS and LIS were also independently associated with diabetes incidence in a multivariate model. Compared to the bottom quartile, the top LIS quartile and the top GRS quartile had a 2.4-fold (95 % CI, 2.0-2.8) and a 1.4-fold (95 % CI, 1.2-1.7) higher diabetes risk, respectively. However, the FDII exhibited null association. When each genetic variant was evaluated, the top versus bottom LIS quartiles exhibited heterogeneous diabetes risks for rs560887 within G6PC2, rs7072268 within HK1, and rs837763 within CDT1; however, these differences were not statistically significant in multiple comparison. CONCLUSION: Both GRS and LIS factors independently affect the incident diabetes, but their interaction effect showed insignificant association. Therefore, regardless of genetic susceptibility, more effort is needed to lower the risk for diabetes by improving lifestyle behaviors.

Effects of the multidomain intervention with nutritional supplements on cognition and gut microbiome in early symptomatic Alzheimer's disease: a randomized controlled trial.

Background: The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer's disease patients. Methods: Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed. Results: The RBANS total scale index score improved significantly in group A compared with group B (p < 0.032) and compared with the control group (p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium. Conclusion: SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer's disease who were amyloid-positive by PET.

Metabolic complications of obesity in children and adolescents.

The global prevalence of childhood and adolescent obesity, exacerbated by the COVID-19 pandemic, is affecting not only school-aged children but also preschoolers. Early-onset obesity, along with a higher risk of metabolic complications, may contribute to a lower age of onset of cardiovascular disease (CVD). As metabolic diseases such as diabetes, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD) observed in adulthood are increasingly recognized in the pediatric population, there is an emphasis on moving disease susceptibility assessment from adulthood to childhood for early detection. Unlike adults, there is a lack of consensus in the definition of metabolic diseases in children. In response to this, various indicators such as pediatric simple metabolic syndrome score (PsiMS), continuous metabolic syndrome score (cMetS), single point insulin sensitivity estimator (SPISE), and fatty liver index (FLI) have been proposed in several studies. These indicators may help explain and early detect metabolic complications associated with pediatric obesity, although more validity studies are needed. Meanwhile, obesity assessment is shifting its perspective from visual obesity to metabolic health and body composition considerations to fill the gap in health impact assessment. Sarcopenic obesity, defined as muscle-to-fat ratio (MFR), has been proposed in pediatric populations and has also been found to be associated with metabolic health in children and adolescents. The National health screening program for children in Korea has expanded but still faces limitations in laboratory testing. These tests facilitate timely intervention by identifying high-risk groups for metabolic complications. Early detection and intervention through comprehensive health screening are critical to mitigate long-term complications of childhood obesity.

Cancer risk based on alcohol consumption levels: a comprehensive systematic review and meta-analysis.

OBJECTIVES: Alcohol consumption is a well-established risk factor for cancer. Despite extensive research into the relationship between alcohol consumption and cancer risk, the effect of light alcohol consumption on cancer risk remains a topic of debate. To contribute to this discourse, we conducted a comprehensive systematic review and meta-analysis. METHODS: Our systematic review aimed to investigate the associations between different levels of alcohol consumption and the risk of several cancer types. We focused on analyzing prospective associations using data from 139 cohort studies. Among them, 106 studies were included in the meta-analysis after a quantitative synthesis. RESULTS: Our analysis did not find a significant association between light alcohol consumption and all-cause cancer risk (relative risk, 1.02; 95% confidence interval, 0.99 to 1.04), but we observed a dose-response relationship. Light alcohol consumption was significantly associated with higher risks of esophageal, colorectal, and breast cancers. Light to moderate drinking was associated with elevated risks of esophageal, colorectal, laryngeal, and breast cancers. Heavy drinking was also found to contribute to the risk of stomach, liver, pancreas, and prostate cancers, thereby increasing the risk of almost all types of cancer. Additionally, females generally had lower cancer risks compared to males. CONCLUSIONS: Our findings highlight that cancer risks extend beyond heavy alcohol consumption to include light alcohol consumption as well. These findings suggest that there is no safe level of alcohol consumption associated with cancer risk. Our results underscore the importance of public health interventions addressing alcohol consumption to mitigate cancer risks.

Effect of 12-week intermittent calorie restriction compared to standard of care in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD can result in various complications. Owing to the lack of effective pharmacological therapies, lifestyle modifications are the cornerstone treatment for NAFLD. However, there has been no recommendation for a specific dietary therapy. Because no significant effects have been observed in previous studies. Intermittent calorie restriction (ICR) consists of alternating phases of extreme energy restriction and regular energy intake. Recent studies have demonstrated a significantly higher reduction in liver fat content in the ICR group than in the standard of care (SOC) or continuous calorie restriction groups in patients with NAFLD. However, critical weaknesses limit the broader application of ICR in clinical practice; those are a lack of appropriate assessment tools, different cutoffs of body mass index (BMI) used to define obesity, and different food portions. Thus, we report a protocol for a prospective, randomized controlled trial. The trial will evaluate the effect of 12-week ICR on improving liver fat content in NAFLD patients (Nonalcoholic Fatty Liver Disease-Intermittent Calorie Restriction [FLICR]). METHODS: We will include adult (19-75 years) NAFLD patients. NAFLD will be diagnosed by histologic assessment or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 8%. A total of 72 patients will be classified according to BMI (obese group: BMI ≥ 25 kg/m2 [n = 36] and non-obese group: BMI < 25 kg/m2 [n = 36]). Participants will be followed up for 24 weeks. Participants will be randomly assigned to one of the two groups: the SOC or ICR group. The primary objective will be the change in liver fat content measured using MRI-PDFF from baseline to 12 weeks. DISCUSSION: This FLICR study may provide clinical evidence on ICR in the treatment of NAFLD in both obese and non-obese patients. The use of ICR in patients with NAFLD will improve the clinical outcomes of patients facing a shortage of effective medical therapy. TRIAL REGISTRATION: This trial was registered at the United States National Library of Medicine (NLM) at the National Institutes of Health. CLINICALTRIALS: gov NCT05309642. Registered on April 4, 2022.

Association between use of vitamin and mineral supplement and non-alcoholic fatty liver disease in hypertensive adults.

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic metabolic disorder in hypertensive adults. Impaired metabolism of micronutrients may increase NAFLD risk by exacerbating oxidative stress, insulin resistance, and inflammation among hypertensive adults. In this first cross-sectional analysis of 7,376 hypertensive adults with 2,015 NAFLD cases in the Korea National Health and Nutrition Examination Survey, vitamin and mineral supplements (VMS) use was identified via questionnaire. NAFLD was defined by a hepatic steatosis index > 36. Multivariable-adjusted odds ratios (MVOR) and 95% confidence intervals (CIs) were calculated using logistic regression models. In our study, 18.6% were current users of VMS; of these, 76.7% used multi-vitamin/mineral supplements. Current VMS users had significantly lower odds of NAFLD, compared with non-users (MVOR [95% CI]: 0.73 [0.58-0.92]). The inverse association became attenuated and non-significant among those consuming VMS at higher frequency (≥ 2 times/day), for longer duration (> 16 months), and taking ≥ 2 VMS products. The inverse association with current use of VMS was only evident in those aged < 56 years (MVOR [95% CI]: 0.54 [0.40-0.72]) and men (MVOR [95% CI]: 0.56 [0.40-0.80])(Pinteraction ≤ 0.04). Our results suggest that VMS use may lower NAFLD risk, particularly among younger or male hypertensive adults, if taken in moderation.

Increase of Prevalence of Obesity and Metabolic Syndrome in Children and Adolescents in Korea during the COVID-19 Pandemic: A Cross-Sectional Study Using the KNHANES.

(1) Background: The aim of this study was to evaluate the prevalence of obesity and metabolic syndrome since the COVID-19 pandemic outbreak utilizing representative data on youth aged 2-18 years from the Korean National Health and Nutrition Examination Surveys (KNHANES) conducted in 2019-2020. (2) Methods: The survey consists of three parts: health interviews, health examinations, and nutrition surveys. From the 2019 and 2020 surveys, 1371 (2-9 years = 702 and 10-18 years = 669) and 1124 (2-9 years = 543 and 10-18 years = 581) individuals were included in the analysis. (3) Results: The mean body mass index (BMI) increased significantly among youth aged 2-9 years from 16.53 kg/m2 in 2019 to 17.1 kg/m2 in 2020 (p < 0.01). In youth aged 10-18 years, the BMI was found to increase slightly from 21.25 kg/m2 in 2019 to 21.41 kg/m2 in 2020 (p = 0.64). The increasing prevalence of extreme obesity was significant in girls, especially those aged 2-9 years (p < 0.01). However, extreme obesity had increased in 10-18-year-old boys (p = 0.08). The overall prevalence of metabolic syndrome in adolescents increased from 3.79% to 7.79% during the COVID-19 pandemic (p = 0.01). (4) Conclusions: We observed that the prevalence of obesity and metabolic syndrome among children and adolescents has increased after the COVID-19 outbreak. This is believed to be associated with an increase in the rate of early comorbidities in adulthood. The prevention of the progression of pediatric obesity has recently become an urgent public health concern in Korea.

Dynamic changing smoking habits and cardiovascular events in patients newly diagnosed with hypertension, diabetes, or dyslipidemia: a national cohort study.

Background and aims: This study aimed to examine the association between dynamic smoking habit change and cardiovascular risk in a population newly diagnosed with hypertension, diabetes, and dyslipidemia. Methods: This study included 49,320 individuals who had received health examinations provided by the Korea National Health Insurance Service. To determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident major adverse cardiac events (MACE) and all-cause mortality based on dynamic smoking habit changes for 2 years, multivariable Cox proportional hazard models were utilized. Results: During the follow-up, there were 1,004 (2.2%), 3,483 (7.6%), and 334 (0.7%) cases of myocardial infarction, stroke events, and cardiovascular death, respectively. The group with worsening smoking habits had an increased risk of cardiovascular events and death (HR: 1.33, 95% CI: 1.26-1.40) compared to improved smoking habits. The robustness of the results determined by a series of sensitivity analyses further strengthened the main findings. Conclusions: Our findings suggest that worsening of smoking habits, even for a short period of time, may increase the risk of myocardial infarction, stroke, and cardiovascular death in patients diagnosed with hypertension, diabetes, and dyslipidemia. For the primary prevention of cardiovascular events in patients with underlying diseases, dynamic modification of smoking habits should be actively considered.

Corrigendum: Clinical implications of atrial fibrillatioN detection using wearabLE devices in patients with cryptogenic stroke (CANDLE-AF) trial: Design and rationale.

[This corrects the article DOI: 10.3389/fcvm.2022.837958.].

Synergistic effect of serum uric acid and body mass index trajectories during middle to late childhood on elevation of liver enzymes in early adolescence: Findings from the Ewha Birth and Growth Study.

BACKGROUND/OBJECTIVES: We aimed to determine whether serum uric acid (SUA) and body mass index (BMI) trajectories in childhood have longitudinal association with liver enzymes in adolescence. METHODS: We conducted a study using data from the Ewha Birth and Growth Cohort. Individual trajectories of SUA (n = 203) and BMI (n = 206) from 5, 7, and 9 years were defined by group-based trajectory modeling. Also, liver function enzymes were collected at 11 to 12 year of age (Aspartate Aminotransferase [AST], Alanine transaminase [ALT], and Gamma-glutamyl transferase [γ-GTP]) (n = 206). Using a generalized linear model, the effects of SUA trajectory and BMI trajectory on liver function enzymes were assessed. We also assessed the interaction effect of SUA and BMI trajectories on liver enzymes. RESULTS: For trajectory patterns, both SUA and BMI were classified into two distinct groups (High or Low). Both trajectory of SUA and BMI in childhood were positively associated with levels of liver enzymes at 11-12 years of age. The results showed that the combined effect of SUA and BMI trajectories on liver enzymes had a higher means in high-risk group (high SUA-high BMI trajectories group) than in low-risk group (low SUA-low BMI trajectories group) for ALT and γ-GTP, respectively. It remained significant association when adjusted for covariates. In addition, the interaction of BMI and SUA trajectories showed a significant synergistic effect. CONCLUSION: Elevated childhood SUA and BMI trajectories are associated with increased liver enzymes in beginning of adolescent. This finding suggesting that early interventions in SUA and BMI may need for optimization of liver enzymes as potential marker for development of related disease in later life.

The association between urinary cotinine level and metabolic syndrome profiles among adolescents: findings from the Ewha Birth and growth study.

BACKGROUND: Secondhand smoke (SHS) exposure among adolescents who are still developing can negatively affect their physical and psychological health, including metabolic syndrome (MetS), which is a risk factor for cardiovascular disease. However, the relationship between exposure to SHS and MetS in adolescence has not been evaluated. METHODS: A total of 240 subjects aged 13-15 years who were followed up in the Ewha Birth and Growth Study were included in this study. Using the urinary cotinine level, the participants' exposure to SHS was divided into tertiles, and the continuous MetS score (cMetS) and its components were compared among the three groups using a generalized linear model and trend analysis. Univariate and multivariate linear regression analyses were performed. We adjusted for several confounding variables including sex, father's education level, father's current alcohol consumption status, moderate physical activity, and overweight status. RESULTS: The association between cMetS and the urinary cotinine level was not significant. However, the higher the urinary cotinine level, the lower the high-density lipoprotein cholesterol (HDL-C) level. In particular, the significance of the HDL-C level was maintained after adjusting for covariates. CONCLUSIONS: This study supports an association between SHS exposure and the components of MetS in adolescents aged 13-15 years, and it suggests the need to address SHS exposure in adolescents to reduce the cardiovascular risk in later life.

Baseline Tyrosine Level Is Associated with Dynamic Changes in FAST Score in NAFLD Patients under Lifestyle Modification.

Noninvasive risk stratification is a challenging issue in the management of patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to identify multiomics-based predictors of NAFLD progression, as assessed by changes in serial FibroScan-aspartate aminotransferase (FAST) scores during lifestyle modification. A total of 266 patients with available metabolomics and genotyping data were included. The follow-up sub-cohort included patients with paired laboratory and transient elastography results (n = 160). The baseline median FAST score was 0.37. The PNPLA3 rs738409 genotype was significantly associated with a FAST score > 0.35. Circulating metabolomics significantly associated with a FAST score > 0.35 included SM C24:0 (odds ratio [OR] = 0.642; 95% confidence interval [CI], 0.463-0.891), PC ae C40:6 (OR = 0.477; 95% CI, 0.340-0.669), lysoPC a C18:2 (OR = 0.570; 95% CI, 0.417-0.779), and tyrosine (OR = 2.743; 95% CI, 1.875-4.014). A combination of these metabolites and PNPLA3 genotype yielded a c-index = 0.948 for predicting a FAST score > 0.35. In the follow-up sub-cohort (median follow-up = 23.7 months), 47/76 patients (61.8%) with a baseline FAST score > 0.35 had a follow-up FAST score ≤ 0.35. An improved FAST score at follow-up was significantly associated with age, serum alanine aminotransferase, and tyrosine. In conclusion, baseline risk stratification in NAFLD patients may be assisted using a multiomics-based model. Particularly, patients with increased tyrosine may benefit from an earlier switch to pharmacologic approaches.

Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study.

BACKGROUND: Phthalate exposure is ubiquitous due to the widespread use of plastic products in daily life, and affects several health outcomes, including metabolic diseases. In this study, we evaluated the effects of phthalate exposure in childhood on liver function in adolescence.  METHODS: Among 164 Ewha Birth and Growth Cohort Study participants followed up during two exposure periods (when the children were aged 3-5 and 7-9 years), 126 were followed up at age 10-15 years. To investigate the relationship between phthalate exposure during the two periods and liver enzyme levels (ALT, AST, γ-GTP) in adolescence, differences between groups and the dose-response relationship were analyzed. In addition, we investigated differences in liver enzymes between groups based on the combined exposure levels (high or low) during the two periods. The interaction effect between phthalates and BMI on liver enzyme levels was evaluated, stratified by sex.  RESULTS: In the 3-5 year-old exposure period, ALT levels tended to increase as MECPP levels increased, while γ-GTP levels tended to increase as MiBP, MnBP, and ∑DBP levels increased. In addition, the group exposed to consistently high levels of phthalates at both time points had higher liver enzyme levels compared to the group that had lower exposure. In particular, the interaction effect between some phthalate metabolites and BMI in 3-5 year olds affected AST and γ-GTP levels in adolescence only in girls. CONCLUSIONS: Exposure to phthalates in daily life during childhood affects liver enzyme levels in adolescence. Elevated liver enzyme levels are associated with the development of metabolic syndrome, implying that attention should be paid to phthalate exposure during childhood.