Multilevel Understanding of the Impact of Individual- and School-Level Determinants on Lipid Profiles in Adolescents: The Cross-Level Interaction of Food Environment and Body Mass Index.

Adolescents with comparable personal risk factors may have different lipid profiles because of the school's context. Lipid determinants in adolescents should be considered using a multilevel perspective. This multilevel study investigated the effects of individual-level and school-level factors on lipid profiles in adolescents and evaluated the cross-level influence of lipid determinants. A representative adolescent cohort (n = 2727) was randomly selected from 36 schools in three diverse economic areas in Taiwan and assessed for their personal dietary patterns, physical parameters, and lipid profiles. For individual-level factors, both low physical activity and high body mass index (BMI) were associated with elevated triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels, and a sugar-sweetened beverage intake of >500 mL/day was associated with increases of 5.97 and 6.12 mg/dL in LDL-C and TC levels, respectively, compared with abstinence. Regarding school-level factors, students in schools with ≥2 health promotion programs per year had a 5.27 mg/dL lower level of LDL-C than those in schools with 0−1 program, and students in schools with ≥46 food outlets within 600 m of the school had 6.90 and 13.3 mg/dL higher levels of TG and TC, respectively, than those in schools with <46 food outlets. School context modified the individual-level positive correlation between BMI and TG level (the p-value for the random-slope effect was 0.003). In conclusion, individual-level and school-level factors exert a multilevel effect on adolescent lipid profiles. The food environment near the school has a stronger cross-level impact on individual TG levels in adolescents with a high BMI than in those with a normal BMI.

Stability and Transformation of Metabolic Syndrome in Adolescents: A Prospective Assessment in Relation to the Change of Cardiometabolic Risk Factors.

Underlying pathophysiological mechanisms drive excessive clustering of cardiometabolic risk factors, causing metabolic syndrome (MetS). MetS status may transform as adolescents transition to young adulthood. This study investigated the latent clustering structure and its stability for MetS during adolescence, and assessed the anthropometric and clinical metabolic determinants for MetS transformation. A community-based representative adolescent cohort (n = 1516) was evaluated for MetS using four diagnostic criteria, and was followed for 2.2 years to identify new-onset MetS. The clustering structure underlying cardiometabolic parameters was stable across adolescence; both comprised a fat-blood pressure (BP)-glucose three-factor structure (total variance explained: 68.8% and 69.7% at baseline and follow-up, respectively). Among adolescents with MetS-negative at baseline, 3.2-4.4% had incident MetS after 2.2 years. Among adolescents with MetS-positive at baseline, 52.0-61.9% experienced MetS remission, and 38.1-48.0% experienced MetS persistence. Increased systolic BP (SBP) was associated with a high MetS incidence risk, while decreased levels of SBP and glucose were associated with MetS remission. Compared with adolescents with a normal metabolic status at baseline, those with an initial abdominal obesity and increased triglycerides level had a 15.0- and 5.7-fold greater risk for persistent abnormality, respectively. Abdominal obesity and low high-density lipoprotein cholesterol are two abnormal MetS components that highly persist during adolescence, and are the intervention targets for reducing the future risk of cardiometabolic disorders.

Contribution of insulin resistance to the relationship between sugar-sweetened beverage intake and a constellation of cardiometabolic abnormalities in adolescents.

BACKGROUND: Insulin resistance (IR) is a pathophysiological construct that derives a series of metabolic disturbances that promote cardiometabolic dysfunction. This study evaluated mediating and modifying effects of homeostatic model assessment-based IR (HOMA-IR) on the association between sugar-sweetened beverage (SSB) consumption and a constellation of adolescent cardiometabolic abnormalities. METHODS: Comprehensive data on sociodemographics, diet, physical activity, and anthropometric and biochemical parameters for 1454 adolescents were obtained from a large-scale representative study for adolescent metabolic syndrome (MetS) conducted in Taiwan. The original (HOMA1-IR) and updated nonlinear (HOMA2-IR) HOMA-IR indicators were used as IR biomarkers. Principal component (PC) analysis was employed to create reduced groups of variables and risk scores for retained PCs. RESULTS: Higher SSB intake was associated with higher levels of HOMA1-IR and HOMA2-IR, and the two IR biomarkers were positively correlated with metabolic dysfunction clustering. Compared with SSB nondrinkers, adolescents who consumed >500 mL/day of hand-shaken high-fructose corn syrup beverages (HHB) had a 0.22 increase in the number of abnormal MetS components, and HOMA-IR mediation explained 33.9-37.9% of the effect. IR biomarkers accounted for 26.5-31.0% of the relationship between >500 mL/day of SSB consumption and bodyweight-enhanced PC scores. The effects of HOMA-IR indicators on all bodyweight-related factors were consistently intensified among >350 mL/day HHB drinkers (all Pinteraction < 0.05). CONCLUSIONS: Fructose-rich SSB intake correlates with a constellation of cardiometabolic abnormalities in adolescents, and this association may be partly mediated by HOMA-IR levels. The adverse effects of HOMA-IR on bodyweight-associated cardiometabolic risk factors depend on the type of SSB consumption, with enhanced risks observed in the intake of high amounts of HFCS-containing SSBs.

Characteristic-Grouped Adiposity Indicators for Identifying Metabolic Syndrome in Adolescents: Develop and Valid Risk Screening Tools Using Dual Population.

A simple, robust, and characterized adiposity indicator may be appropriate to be used as a risk screening tool for identifying metabolic syndrome (MetS) in adolescents. This study used dual adolescent populations to develop and validate efficient adiposity indicators from 12 characterized candidates for identifying MetS that may occur during the transition from adolescence to young adulthood. Data from the adolescent Nutrition and Health Survey in Taiwan (n = 1920, 12-18 years) and the multilevel Risk Profiles for adolescent MetS study (n = 2727, 12-16 years) were respectively used as training and validation datasets. The diagnostic criteria defined by the International Diabetes Federation for adolescents (IDF-adoMetS) and the Joint Interim Statement for adults (JIS-AdMetS) were employed to evaluate MetS. In the training dataset, principal component analysis converted 12 interrelated obesity indices into bodyfat-, lipid-, and body-shape-enhanced groups, with the first two characteristic-groups having a higher discriminatory capability in identifying IDF-adoMetS and JIS-AdMetS. In the validation dataset, abdominal volume index (AVI) among girls and waist circumference (WC) among boys were respectively validated to have a higher Youden's index (0.740-0.816 and 0.798-0.884) in identifying the two MetS. Every 7.4 and 4.3 positive tests of AVI (cutoff = 13.96) had an accurate IDF-adoMetS and JIS-AdMetS, respectively, and every 32.4 total tests of WC (cutoff = 90.5 cm) had a correct identification for the two MetS. This study stresses the discriminatory capability of bodyfat- and lipid-enhanced adiposity indicators for identifying MetS. AVI and WC were, respectively, supported as a risk screening tool for identifying female and male MetS as adolescents transition to adulthood.

Clustering of Metabolic Risk Components and Associated Lifestyle Factors: A Nationwide Adolescent Study in Taiwan.

Clustering of metabolic syndrome (MetS) risk components in childhood has been linked to a higher risk of diabetes and cardiovascular diseases in adulthood. By using data from the 2010⁻2011 Nutrition and Health Survey in Taiwan, this study investigated epidemic patterns and correlates for the clustering of MetS risk components. A total of 1920 adolescents aged 12⁻18 years were included in this study. The MetS diagnostic criteria defined by the Taiwan Pediatric Association (TPA) and International Diabetes Federation (IDF) for adolescents and the criteria defined by the Joint Interim Statement for adults (JIS-Adult) were used to evaluate MetS and its abnormal components. The prevalence of TPA-, IDF-, and JIS-Adult-defined MetS was 4.1%, 3.0%, and 4.0%, with 22.1%, 19.3%, and 17.7%⁻18.1% of adolescents having high fasting glucose, low high-density lipoprotein cholesterol, and central obesity, respectively. A 0.4-to-0.5-fold decreased risk of having ≥2 MetS abnormal components was detected among adolescents who consumed ≥1 serving/week of dairy products and fresh fruits. Boys who consumed ≥7 drinks/week of soda and girls who consumed ≥7 drinks/week of tea had a 4.6- and 5.2-fold risk of MetS, respectively. In conclusion, our findings revealed significant dimensions of adolescent MetS, including detecting population-specific prevalent patterns for MetS risk components and their clustering, and emphasized on health promotion activities that reduce sugar-sweetened beverage intake.

Effects of insulin resistance on the association between the circulating retinol-binding protein 4 level and clustering of pediatric cardiometabolic risk factors.

OBJECTIVES: Retinol-binding protein 4 (RBP4) and insulin resistance (IR) are clinical parameters associated with cardiometabolic diseases. The mediating and modifying roles of IR on children's susceptibility to cardiometabolic disorders are undetermined. This study investigated the mediating and modifying effects of the homeostatic model assessment of IR (HOMA-IR) on the relationship between the serum RBP4 level and clustering of pediatric cardiometabolic risk factors. METHODS: We assessed the diet, physical activity, cardiometabolic risk factors, and clinical parameters of 272 randomly selected adolescents from a large-scale cross-sectional study (n = 2727). Two HOMA-IRs (HOMA1-IR and HOMA2-IR) were used to evaluate the designated effects. RESULTS: Levels of serum RBP4 positively correlated with the levels of the 2 HOMA-based-IRs, and HOMA-IR correlated to all components of pediatric metabolic syndrome (MetS), the number of abnormal components, and a body-weight-weighted principal component score extracted from 12 cardiometabolic risk factors. Increased RBP4 levels had positive effects on waist circumference (WC), triglyceride, and the number of abnormal MetS components (0.310 cm, 1.384 µg/dL, and 0.021 item elevations, respectively), and the HOMA-IRs explained 17.7% to 21.9%, 11.8% to 27.6%, and 23.8% to 25.0% of these effects. The association of WC and the number of abnormal MetS components with the serum RBP4 level was enhanced by higher HOMA-IR (ß for interaction, 0.13 and 0.01 for HOMA1-IR, and 0.32 and 0.02 for HOMA2-IR, respectively). CONCLUSIONS: HOMA-IR is associated with the circulating RBP4 level and cardiometabolic risk factors in adolescents. Pediatric HOMA-IR may have mediating and modifying effects on the positive correlations between RBP4 and the clustering of MetS components.

Association of Parental Overweight and Cardiometabolic Diseases and Pediatric Adiposity and Lifestyle Factors with Cardiovascular Risk Factor Clustering in Adolescents.

Cardiometabolic risk factors or their precursors are observed in childhood and may continue into adulthood. We investigated the effects of parental overweight and cardiometabolic diseases and pediatric lifestyle factors on the clustering of cardiovascular risk factors among adolescents, and examined the mediating and modifying effects of pediatric adiposity on these associations. Representative adolescents (n = 2727; age, 12-16 years) were randomly recruited through multistage stratified sampling from 36 schools in Southern Taiwan. Adolescent and parent surveys were conducted in schools and participant homes, respectively. Their demographic factors, diet patterns, and physical, anthropometric, and clinical parameters were collected and analyzed. Adolescents with 1-2 and ≥3 risk components for pediatric metabolic syndrome (MetS) were defined as potential MetS (pot-MetS) and MetS, respectively. Adolescents whose parents were overweight/obese, or with diabetes and hypertension had a higher prevalence ratio of pot-MetS and MetS (1.5-1.6 and 1.9-4.2-fold, respectively). Low physical activity (<952.4 MET·min/week), long screen time (≥3 h/day) and high sugar-sweetened beverage intake (>500 mL/day) were associated with a 3.3- (95% confidence intervals (CI) = 1.5-7.3), 2.2- (95% CI = 1.1-4.4), and 26.9-fold (95% CI = 3.2-229.0) odds ratio (OR) of MetS, respectively. Pediatric body mass index (BMI) accounted for 18.8%-95.6% and 16.9%-60.3% increased prevalence ratios of these parental and pediatric risk factors for MetS. The OR of pot-MetS + MetS for sugar-sweetened beverage consumption was multiplicatively enhanced among adolescents with overweight/obesity (combined OR, 8.6-fold (95% CI = 4.3-17.3); p for multiplicative interaction, 0.009). The results suggest that parental overweight and cardiometabolic diseases and pediatric sedentary and high sugar-intake lifestyles correlate with the development of adolescent MetS, and an elevated child BMI explains a part of these associations. Pediatric adiposity might be multiplicatively associated with sugar-sweetened beverage consumption for enhancing the MetS prevalence ratio among adolescents.

Fructose-Rich Beverage Intake and Central Adiposity, Uric Acid, and Pediatric Insulin Resistance.

OBJECTIVE: To determine the association between sugar-sweetened beverage (SSB) consumption with biomarkers of insulin resistance (IR) and investigate whether/how this relates to obesity and serum uric acid in adolescents. STUDY DESIGN: Adolescents (n = 1454, aged 12-16 years) were assessed in a study conducted to monitor Multilevel Risk Profiles for Adolescent Metabolic Syndrome in Taiwan. Detailed information about demographics, diet, physical, anthropometric, and clinical variables was collected. An original homeostatic model assessment of IR (HOMA1-IR), updated nonlinear homeostatic model assessment of IR (HOMA2-IR) model, and several IR markers were measured. RESULTS: Adolescents who consumed a greater amount of SSBs were more likely to have elevated fasting serum insulin, HOMA1-IR, and HOMA2-IR (P for trends, ≤.028). Compared with SSB nondrinkers, those with >350 mL/d intake of heavy high-fructose corn syrup-containing SSBs had a 0.52 and 0.30 higher multivariate-adjusted HOMA1-IR and HOMA2-IR, respectively. Waist circumference and serum uric acid were correspondingly found to explain 25.4% and 23.6%, as well as 23.2% and 20.6%, of the increases in the 2 IR markers. Both the elevations of HOMA1-IR and HOMA2-IR for high-fructose corn syrup-rich SSB intake were strengthened among obese adolescents (P for interaction, ≤.033). CONCLUSIONS: Fructose-rich SSB intake is associated with elevated levels of IR, and this relationship may be partially mediated by central adiposity and serum uric acid. Obesity may modify the effect of this type of SSB consumption in intensifying the elevation of IR in adolescents.

Consumption of sugar-sweetened beverages is associated with components of the metabolic syndrome in adolescents.

Sugar-sweetened beverages (SSBs) are the principle source of added sugar in diets. Cardiometabolic disturbances can occur from early childhood to adulthood. The aim of this cross-sectional study was to examine the gender-specific association of SSB intake with metabolic syndrome (MetS) and its components among adolescents in Taiwan. A total of 2727 adolescents aged 12 to 16 years randomly selected from three diverse economic areas in Southern Taiwan by using a multistage-sampling strategy participated in this study. Demographic, dietary, physical and anthropometric parameters were measured, and serum lipid profiles and glucose levels were determined. The International Diabetes Federation (IDF) specifies that MetS requires abdominal obesity and ≥2 abnormal components, and Cook criteria for MetS require ≥3 abnormal components. We applied survey-data modules to data analyses, and used multiple regression and logistic models to adjust for covariates. An increased SSB intake was linked to a greater waist circumference in both sexes and to systolic blood pressure in boys (P for trend: ≤0.043). Male moderate and high consuming SSB drinkers exhibited triglyceride levels that were 8.0 and 8.2 mg/dL significantly higher, respectively, than those of nondrinkers. Compared with nondrinkers, boys who consumed >500 mL/day (high quantity) of SSBs exhibited 10.3-fold (95% confidence intervals (CIs): 1.2-90.2) and 5.1-fold (95% CIs: 1.01-25.5) risks of contracting MetS, as defined by the IDF and Cook criteria for MetS, respectively. In girls, the risk estimates for the same comparison were not significant by the IDF criteria (6.5-fold risk, 95% CIs: 0.9-∞) or Cook criteria (5.9-fold risk, 95% CIs: 0.8-43.8) for MetS. High SSB consumption was also linked to 1.9-fold (95% CIs: 1.1-3.1) and 2.7-fold (95% CIs: 1.3-5.7) higher risks of being at a greater overall metabolic risk in girls and boys, respectively. In conclusion, a high SSB intake is associated with adolescent MetS among boys but not girls in Taiwan.

Elevated serum triglyceride and retinol-binding protein 4 levels associated with fructose-sweetened beverages in adolescents.

BACKGROUND: The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. OBJECTIVES: This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. METHODS: We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. RESULTS: Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r = 0.253 to 0.404), but not among non-drinkers. CONCLUSIONS: High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4.

P-selectin-dependent platelet aggregation and apoptosis may explain the decrease in platelet count during Helicobacter pylori infection.

P-selectin expression has been shown in Helicobacter pylori-infected persons, an infection that has been clinically associated with platelet-related diseases, such as idiopathic thrombocytopenic purpura. However, the role of P-selectin expression during H pylori infection remains unclear. In this study, we hypothesized that P-selectin expression was associated with platelet aggregation during H pylori infection. Using flow cytometry, we examined the levels of adhesion between H pylori and platelets as well as the levels of P-selectin expression and platelet phosphatidylserine (PS) expression during H pylori infection. Significantly high levels of adhesion between pro-aggregatory bacteria and platelets were observed. We identified that H pylori IgG is required for bacteria to induce P-selectin expression and that a significant release of P-selectin is essential for H pylori to induce aggregation. In addition, cellular apoptotic signs, such as membrane blebbing, were observed in platelet aggregates. PS expression was also detected in platelets during infection with both pro-aggrogatory and nonaggregatory strains of H pylori. These results suggest that the decrease in platelet counts seen during H pylori infection is the result of P-selection-dependent platelet aggregation and PS expression induced by the bacteria.

The precancerous effect of emitted cooking oil fumes on precursor lesions of cervical cancer.

Although cooking emission from high-temperature frying has been deemed a Group 2A carcinogen by the International Agency for Research on Cancer, little is known about its impact on cervical tumorigenesis. To investigate the precancerous consequence of cooking oil fumes on cervical intraepithelial neoplasm (CIN), a community-based case-control study, which takes all known risk factors into consideration, was conducted in Taiwan. From 2003 to 2008, in a Pap smear screening and biopsy examination network, 206 pathology-verified women with inflammations/atypical squamous cells of undetermined significance or CIN grade-1 (CIN1) and 73 with CIN2-3 (defined as low-grade squamous intraepithelial lesions (LGSIL) and high-grade squamous intraepithelial lesions (HGSIL), respectively); and 1,200 area-and-age-matched controls with negative cytology were recruited. Multinomial logistic regression was applied in the multivariate analysis to determine the likelihood of contracting LGSIL or HGSIL. The risks of the two lesions increased with the increase of carcinogenic high-risk human papillomavirus DNA load, with a clear dose-response relationship. Chefs were observed to experience a 7.9-fold elevated HGSIL risk. Kitchens with poor fume ventilation during the main cooking life-stage correlated to a 3.7-fold risk of HGSIL, but not for LGSIL. More than 1 hr of daily cooking in kitchens with poor fume conditions appeared to confer an 8.4-fold HGSIL risk, with an 8.3-fold heterogeneously higher odds ratio than that (aOR = 1.0) for LGSIL. Similar risk pattern has been reproduced among never-smoking women. Our findings demonstrate the association between indoor exposure to cooking fumes from heated oil and the late development of cervical precancerous lesions. This final conclusion needs to be verified by future research.

Association between serum leptin and adiponectin levels with risk of insulin resistance and impaired glucose tolerance in non-diabetic women.

Obesity is a well known risk factor for insulin resistance and type 2 diabetes. Recently discovered adipocyte-derived proteins (leptin and adiponectin) might contribute to the pathologic mechanism linking obesity and insulin resistance. A total of 190 non-diabetic women were recruited from the Obesity Clinic of Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, between February 2003 and February 2004. All participants completed a simple questionnaire. Blood pressure and body mass index were measured; blood samples for fasting glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, leptin, adiponectin, and fasting insulin level were collected after an overnight fast. Two-hour glucose level after a 75-g glucose tolerance test was determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as the index of insulin resistance. Multivariate linear regression analyses were used to analyze the relationship between adipocytokines and insulin resistance after adjusting for possible confounding factors. Leptin and adiponectin were found to be independently associated with HOMA-IR and fasting insulin concentration, but in divergent directions, after adjusting for potential confounding factors. Adiponectin, but not leptin, was associated with impaired glucose tolerance after adjusting for potential confounding factors. The results suggest that leptin and adiponectin may be involved in the pathophysiologic link between obesity and insulin resistance independently. Low levels of adiponectin may increase the risks of developing impaired glucose metabolism and type 2 diabetes.

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis.

Genetic variants in alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes modulate acetaldehyde removal upon alcohol ingestion. Although these genetic vulnerabilities have been linked to higher esophageal squamous cell carcinoma (ESCC) risks, it is unclear whether they also determine the time of malignancy presentation. The purpose of this investigation was to unravel genotoxic effects of the two alcohol-metabolizing genes with regard to alcohol and tobacco consumption on the age at ESCC diagnosis and tumor dissemination. ADH1B/ALDH2 genotyping was performed on lymphocyte DNA specimens taken from 406 consecutively registered incident patients with pathology-proven ESCC. To fully utilize individual genetic and survival information, survival analyses and gene-longevity applied approaches were introduced. Among heavy drinkers, the ADH1B Arg/Arg (55 years) and ALDH2 Glu/Lys genotypes (54 years) were found to confer a 15 and 16 years earlier carcinoma diagnosed age than His/His and Glu/Glu nondrinkers (both 70 years), respectively. For drinkers, 1-year age advancement was, separately, associated with a 0.977 and 0.953-fold stepwise reduced likelihood of being ADH1B Arg homozygote and ALDH2 Lys variant. Noticeably elevated hazard-ratio (HR) for drinkers of ADH1B slow-form genotype and ALDH2 inactive-form allele were identified in smokers (HR = 2.3-2.6), but no in nonsmokers. In smokers, appreciably higher cumulative cancer onset risks were correspondingly recognized from the age of 45 and 49 upward among any + Lys allele and Arg/Arg + Glu/Glu combined-ADH1B/ALDH2-genotype drinkers than nondrinkers. In conclusion, consumption of tobacco and alcohol, coupled with genetic susceptibilities associated with acetaldehyde elimination, as modulated by ADH1B and ALDH2 genotypes, determines a substantial magnitude of tumorigenetic effect on earlier age ESCC diagnosis.