Uric acid mediated the relationship between obesity and hypertension in children and adolescents: A population­based cohort study.

BACKGROUND AND AIM: Obesity and hyperuricemia (HUA) often coexist and have been widely accepted as risk factors for hypertension, but the role of uric acid (UA) in the relationship between obesity and hypertension remains unknown in children and adolescents. METHODS AND RESULTS: A total of 7525 subjects aged 6-16 years were from the School-based Cardiovascular and Bone Health Promotion Program (SCVBH) at baseline (2017) and followed up in 2019. Multivariable logistic regression with interaction terms, cross-lagged panel analysis, and causal mediation model were applied to delineate the joint impact of obesity and HUA on hypertension, including the interaction effect, the temporal association, and the mediating effect of UA in the relationship between obesity and hypertension. There were 10.8 % of the participants with normotension at baseline developed hypertension after two years of follow-up. Cross-lagged panel analysis showed that the two-time point association was significant only from baseline BMI to follow-up UA (ß1 = 0.302, P < 0.001), but not from baseline UA to follow-up BMI (ß2 = 0.002, P = 0.745). Multivariable logistic regression showed that both obesity and HUA increased the risk of hypertension, but no interaction effect between HUA and obesity. The causal mediation analysis found that UA partially mediated the association between BMI and SBP (mediate proportion: 20.3 %, 95 % CI: 17.4-22.9 %) or DBP (mediate proportion: 11.9 %, 95 % CI: 3.9-18.2 %). The results were consistent in the analysis of systolic hypertension rather than diastolic hypertension. CONCLUSIONS: It is mediating effect that UA played in the progress from obesity to hypertension, particularly systolic hypertension in children and adolescents.

Bidirectional temporal relationships between uric acid and insulin and their joint impact on incident diabetes.

BACKGROUND AND AIMS: This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults. METHODS AND RESULTS: The cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later. After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%). CONCLUSIONS: The bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM.

Life-Course Cumulative Burden of Body Mass Index and Blood Pressure on Progression of Left Ventricular Mass and Geometry in Midlife: The Bogalusa Heart Study.

RATIONALE: Data are limited regarding the influence of life-course cumulative burden of increased body mass index (BMI) and elevated blood pressure (BP) on the progression of left ventricular (LV) geometric remodeling in midlife. OBJECTIVE: To investigate the dynamic changes in LV mass and LV geometry over 6.4 years during midlife and to examine whether the adverse progression of LV geometric remodeling is influenced by the cumulative burden of BMI and BP from childhood to adulthood. METHODS AND RESULTS: The study consisted of 877 adults (604 whites and 273 blacks; 355 males; mean age=41.4 years at follow-up) who had 5 to 15 examinations of BMI and BP from childhood and 2 examinations of LV dimensions at baseline and follow-up 6.4 years apart during adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and systolic BP (SBP). After adjusting for age, race, sex, smoking, alcohol drinking, and baseline LV mass index, the annual increase rate of LV mass index was associated with all BMI measures (ß=0.16-0.36, P<0.05 for all), adult SBP (ß=0.07, P=0.04), and total AUC of SBP (ß=0.09, P=0.01) but not with childhood and incremental AUC values of SBP. All BMI and SBP measures (except childhood SBP) were significantly associated with increased risk of incident LV hypertrophy, with odds ratios of BMI (odds ratio=1.85-2.74, P<0.05 for all) being significantly greater than those of SBP (odds ratio=1.09-1.34, P<0.05 for all except childhood SBP). In addition, all BMI measures were significantly and positively associated with incident eccentric and concentric LV hypertrophy. CONCLUSIONS: Life-course cumulative burden of BMI and BP is associated with the development of LV hypertrophy in midlife, with BMI showing stronger associations than BP. Visual Overview: An online visual overview is available for this article.

Temporal relationship between body mass index and uric acid and their joint impact on blood pressure in children and adults: the Bogalusa Heart Study.

OBJECTIVE: This study aimed to examine the temporal relationship between body mass index (BMI) and uric acid (UA), and their joint effect on blood pressure (BP) in children and adults. METHODS: The longitudinal cohorts for temporal relationship analyses consisted of 564 and 911 subjects examined twice 5-14 years apart from childhood to adulthood. The cross-sectional cohorts for mediation analyses consisted of 3102 children and 3402 nondiabetic adults. Cross-lagged panel analysis models were used to examine the temporal relationship between BMI and UA, and mediation analysis models the mediation effect of UA on the BMI-BP association. RESULTS: After adjusting for age, race, sex and follow-up years in children, and additionally smoking and alcohol drinking in adults, the path coefficients (standardized regression coefficients) from baseline BMI to follow-up UA (0.145 in children and 0.068 in adults) were significant, but the path coefficients from baseline UA to follow-up BMI (0.011 in children and 0.016 in adults) were not. In mediation analyses, indirect effects through UA on the BMI-systolic BP association were estimated at 0.028 (mediation effect = 8.8%) in children and 0.033 (mediation effect = 13.5%) in adults (P < 0.001 for both). Direct effects of BMI on systolic BP (0.289 in children and 0.212 in adults) were significant. The mediation effect parameters did not differ significantly between Blacks and Whites. CONCLUSIONS: Changes in BMI precede alterations in UA, and the BMI-BP association is in part mediated through BMI-related increase in UA both in children and in adults. These findings have implications for addressing mechanisms of obesity hypertension beginning in early life.

High BMI with Adequate Lean Mass Is Not Associated with Cardiometabolic Risk Factors in Children and Adolescents.

BACKGROUND: Despite an increasing number of studies investigating the links between increased BMI and a better prognosis of cardiovascular disease, which has been termed the "obesity paradox," few of them take the lean mass into consideration. OBJECTIVES: This study aimed to explore the associations of body composition compartments, especially the lean mass, with cardiometabolic abnormalities in children and adolescents. METHODS: In a nationwide cross-sectional study of 6- to 18-y-old children (n = 8967, 50.1% boys), we measured body composition using DXA scan, and calculated BMI, fat mass index (FMI), and lean mass index (LMI). The exploratory outcomes were cardiometabolic abnormalities, including hypertension, dyslipidemia, hyperglycemia, and insulin resistance. Adjusted linear regression coefficients and ORs were calculated to assess the associations between body composition indicators and cardiometabolic abnormalities. RESULTS: Unlike BMI and FMI, LMI was inversely associated with homeostasis model assessment of insulin resistance (ß: -0.06; 95% CI: -0.09, -0.03; P < 0.001), fasting plasma glucose (ß: -0.08; 95% CI: -0.11, -0.05; P < 0.001), non-HDL cholesterol (ß: -0.10; 95% CI: -0.13, -0.08; P < 0.001), LDL cholesterol (ß: -0.12; 95% CI: -0.14, -0.09; P < 0.001), and total cholesterol (TC) (ß: -0.16; 95% CI: -0.19, -0.14; P < 0.001). After multivariable adjustment, all the odds of cardiometabolic abnormalities were increased from the lowest quartile to the highest quartile of BMI and FMI (P-trend < 0.05); however, the odds of high TC, high LDL cholesterol, hyperglycemia, and insulin resistance were decreased with LMI (P-trend < 0.05). Obese children with high LMI did not have significantly increased odds of high TC, high LDL cholesterol, and high non-HDL cholesterol compared with normal-weight children without high LMI. CONCLUSIONS: Greater lean mass may have a protective impact on high TC, high LDL cholesterol, hyperglycemia, and insulin resistance in children and adolescents. This finding suggests that the "obesity paradox" may be partly explained by high lean mass.

Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study.

BACKGROUND: Human epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure. METHODS: 55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded. RESULTS: Serum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml, p < 0.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (r = 0.331, p < 0.01) and right atrial pressure (r = 0.30, p < 0.03). After a mean follow-up of 20 ± 10 months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels > 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ2: 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55, p < 0.02) and pulmonary vascular resistance (χ 2: 4.19; HR = 1.14; 95% confidence interval: 1.00-1.29, p < 0.04) were independently predictive of clinical worsening. Patients with HE4 > 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%, p < 0.001). CONCLUSIONS: Serum levels of HE4 were elevated in IPAH patients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAH patients.

Temporal relationship between inflammation and insulin resistance and their joint effect on hyperglycemia: the Bogalusa Heart Study.

BACKGROUND: Inflammation and insulin resistance play crucial roles in the development of type 2 diabetes mellitus (T2DM). We aim to examine the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and insulin resistance in non-diabetic adults and their joint effect on the development of hyperglycemia. METHODS: The longitudinal cohort from the Bogalusa Heart Study consisted of 509 non-diabetic adults (360 whites and 149 blacks, mean age = 42.8 years at follow-up) who had hsCRP, fasting glucose and insulin measured twice at baseline and follow-up over 6.8 years. Cross-lagged panel model was used to examine the temporal relationship between hsCRP and homeostasis model assessment for insulin resistance (HOMA-IR). Information on incident T2DM was collected in a survey in 6.1 years after the follow-up survey. RESULTS: After adjusting for race, sex, age, body mass index, smoking, alcohol drinking and follow-up years, the path coefficient from baseline hsCRP to follow-up HOMA-IR (ß2 = 0.105, p = 0.009) was significant and greater than the path from baseline HOMA-IR to follow-up hsCRP (ß1 = 0.005, p = 0.903), with p = 0.011 for the difference between ß1 and ß2. This one-directional path from baseline hsCRP to follow-up HOMA-IR was significant in the hyperglycemia group but not in the normoglycemia group. In addition, participants with high levels of baseline hsCRP and follow-up HOMA-IR had greater risks of T2DM (odds ratio, OR = 2.38, p = 0.035), pre-T2DM (OR = 2.27, p = 0.006) and hyperglycemia (OR = 2.18, p = 0.003) than those with low-low levels. CONCLUSIONS: These findings suggest that elevated hsCRP is associated with future insulin resistance in non-diabetic adults, and their joint effect is predictive of the development of T2DM.

Body fat indicators perform better than body mass index in identifying abnormal lipid profiles in boys but not in girls.

BACKGROUND: BMI as a body weight indicator, may inadequately represent the biological effect of body fat on lipid profiles. This study aims to assess whether body fat indicators were superior to BMI for recognizing children with dyslipidemia. METHODS: A nationwide cross-sectional study involving 8944 pediatric participants aged 6-18 years. Measures of fat mass index (FMI), fat mass percentage (FMP), BMI, and four lipid profiles were obtained. RESULTS: Among boys, the standard multi-linear regression coefficients of FMI for TC, LDL-C, and TG were higher than those of BMI (P < 0.01), but not for HDL-C. Also, the prevalence ratios and area under curves (AUCs) of excess fat classified by FMI for specific abnormal lipid profiles (except for HDL-C) were greater than overweight classified by BMI. The AUCs for detecting children with abnormal TC, LDL-C, and TG of FMI-based excess fat were 3.9%, 5.6%, and 2.8% higher than those of BMI-based overweight, respectively, all P < 0.01. Among girls, the associations of BMI with lipid profiles were substantially similar to FMI. All these results were almost identical when FMP was used instead of FMI. CONCLUSIONS: DXA measured body fat performs better than BMI in identifying abnormal lipid profiles in boys but not in girls.

Adipokines are Associated With Hypertension in Metabolically Healthy Obese (MHO) Children and Adolescents: A Prospective Population-Based Cohort Study.

BACKGROUND: The potential mechanism underlying the relationship between the risk of cardiovascular diseases and metabolically healthy obese (MHO) individuals remains unclear. The aim of the study was to prospectively investigate the potential role of the adipokines in the association between the MHO phenotype and hypertension in children and adolescents. METHODS: A total of 1184 participants at baseline were recruited from a cohort of the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. The participants were classified according to their body mass index (BMI) and metabolic syndrome (MS) components. The levels of the adipokines, including leptin, adiponectin, and resistin, were measured. RESULTS: MHO individuals had higher leptin levels (11.58 ug/L vs 1.20 ug/L), leptin/adiponectin ratio (1.18 vs 0.07), and lower adiponectin (11.65 ug/L vs 15.64 ug/L) levels compared to metabolically healthy normal-weight individuals (all P < 0.05). Compared to metabolically healthy normal-weight individuals, the prevalence of high leptin levels (26.5% vs 0.4%), low adiponectin levels (17.9% vs 6.3%) and a high leptin/adiponectin ratio (26.0% vs 2.1%) was higher in MHO individuals (all P < 0.01). The MHO individuals with abnormal adipokines were significantly more likely to developing hypertension (high leptin, relative risk 11.04; 95% confidence interval, 1.18-103.35; and high leptin/adiponectin ratio, relative risk 9.88; 95% confidence interval, 1.11-87.97) compared to metabolically healthy normal-weight individuals with normal adipokine levels. CONCLUSIONS: The abnormal adipokine levels contribute to the increased hypertension risk in MHO children and adolescents. The non-traditional risk factors should be highlighted in MHO children and adolescents in clinical practice and research.

10-Year Trends in Serum Lipid Levels and Dyslipidemia Among Children and Adolescents From Several Schools in Beijing, China.

BACKGROUND: Serum lipid trends in children and adolescents are predictors of the future prevalence of cardiovascular disease in adults. METHODS: Data were obtained from cross-sectional studies conducted in 2004 and 2014. A total of 3249 children aged 6-18 years were included in the present study; serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured. RESULTS: Overall, upward trends in mean TC, non-HDL-C, and LDL-C levels, and in geometric mean TG levels, were observed (all P < 0.001). Mean HDL-C levels significantly decreased between 2004 and 2014 (from 1.54 mmol/L to 1.47 mmol/L; P < 0.001). The prevalence of abnormal levels of serum lipids, with the exception of the prevalence of low HDL-C (P = 0.503), significantly increased over the study period (all P < 0.05). The prevalence of hyperlipidemia (from 13.3%; 95% confidence interval [CI], 11.6%-15.0% to 24.5%; 95% CI, 22.4%-26.6%; P < 0.001) and dyslipidemia (from 18.8%; 95% CI, 16.9%-20.7% to 28.9%; 95% CI, 26.7%-31.3%; P < 0.001) also increased from 2004 to 2014. The prevalence of abnormal serum lipids increased, and mean serum lipid levels, with the exception of TC levels, worsened in subjects with obesity compared with non-overweight subjects, as well as in subjects with mixed obesity compared with non-obese subjects (P < 0.05 for all). CONCLUSIONS: Adverse trends in serum lipid concentrations over the past 10 years were observed among children aged 6-9 years, with the exception of specific lipids, and among adolescents aged 10-18 years, from several schools in Beijing, China.

[Association of childhood and adolescents obesity with adult diabetes].

OBJECTIVE: To investigate the correlation between obesity in children and diabetes in adults from a cohort study, and further more to explore the necessity of preventing diabetes by controlling obesity in children. METHODS: In 1987, 3 198 children and adolescents aged 6-18 were recruited from 6 elementary schools and 6 high schools located in 3 districts (Chaoyang, Haidian, and Xicheng) of Beijing using stratified cluster sampling design. The physical examination process included physical development test, blood pressure measurement, and questionnaire investigation. All children were invited to participate in the study, except for those who had history of congenital heart disease, chronic kidney disease, and limb disability. A total of 1,225 adults were enrolled in a prospective follow-up study from March 2010 to July 2012, anthropometric measures and blood sample were obtained. The obesity was defined by the following criteria: for children aged 6, the age-and the gender-specific 95th percentile of BMI from the US Centre for Disease Control and Prevention Growth charts 2000 as the baseline; for children age 7-18, recommendation from Working Group on Obesity in China (WGOC) as the standard; for adults, BMI≥28 kg/m(2) as the diagnosis standard. Diabetes was defined based on fasting plasma glucose(FPG) ≥7.0 mmol/L or 2 hours postprandial blood glucose (2 h PG) ≥11.1 mmol/L or glycosylated hemoglobin (HbA1c) ≥6.5% or current using blood glucose-lowering agents or current using insulin. Logistic regression was used to analyze the association obesity in children with diabetes in adults. RESULTS: The prevalence of diabetes diagnosed by FPG and 2 h PG in adults who were obese children (16.2%, 18/111) was higher than those who were non-obese children (5.6%, 62/1,114)(χ(2)=18.76, P<0.001). The prevalence of diabetes diagnosed by HbA1c in adults who were obese children(18.1%,20/111) was higher than those who were non-obese children (6.9%, 77/1,114) (χ(2)=16.66, P<0.001). With multi-factor logistic regression analysis, we found that after controlling follow-up age, genders and lifestyle (smoking, alcohol consuming, dietary, and sleeping), in comparison with those non-obese from childhood to adulthood, those obese only in childhood or only in adulthood did not predict any risk of diabetes diagnosed by blood glucose in adults (OR(95%CI) were 1.90 (0.86-4.19), 1.71(0.50-5.79), respectively). Those obese both in childhood and in adulthood increased the risk of diabetes diagnosed by blood glucose in adults (OR(95%CI) was 4.50(2.22-9.14)). With multi-factor logistic regression analysis, we found that after controlling age, sex and lifestyle (smoking, alcohol consuming, dietary, and sleeping) in comparison with those non-obese from childhood to adulthood, those obese only in childhood or only in adulthood did not increase the risk of diabetes diagnosed by HbA1c in adults (OR(95%CI) were 1.42(0.71-2.86), 3.13(0.83-11.75), respectively). Those obese both in childhood and in adulthood increased the risk of diabetes diagnosed by HbA1c in adults (OR(95%CI) was 5.93(3.06- 11.49)). CONCLUSION: Obesity in children even sustained to adulthood was a risk factor for diabetes in adulthood. It is necessary to control obesity in children to prevent diabetes in adults.

[Effect of childhood adiposity on long-term risks of carotid atherosclerosis and arterial stiffness in adulthood].

OBJECTIVE: To observe the effect of childhood excessive adiposity on long-term risk of adult carotid atherosclerosis and arterial stiffness. METHODS: At baseline, in 1987, by using stratified cluster sampling design, 3 198 healthy children aged 6-18 were recruited from six primary schools and six middle schools from three districts (Chaoyang, Xicheng, and Haidian) in Beijing, with blood pressure, weight, height and left scapular skinfold thickness (LSSF) measured. From April 2010 to July 2012, 1 225 subjects were followed from childhood to adulthood. Questionnaire, biochemistry parameters, carotid-femoral pulse wave velocity (cfPWV), and carotid intima media thickness (cIMT) were measured at follow-up. Based on weight statuses in childhood and adulthood, subjects were classified into four groups (persistent non-overweight from childhood to adulthood, overweight in childhood but non-overweight in adulthood, non-overweight in childhood but overweight in adulthood, persistent overweight from childhood to adulthood). Multiple logistic regression model was used to analyze the association between weight statuses changing from childhood to adulthood and adult high cfPWV and high cIMT. RESULTS: The prevalence of overweight (including obesity) at adulthood was 52.2% (639). Males had higher prevalence of smoking (62.5%(422/675) vs 29.4%(160/550), χ(2)=133.21, P<0.001), drinking (52.1%(353/675) vs 26.1%(140/550), χ(2)=87.13, P<0.001), overweight (including obesity) (69.3% (468/675) vs 31.1% (171/550), χ(2)=182.18, P< 0.001) than females. With adjusting for gender, age, and length of follow-up, the risk of high cfPWV and high cIMT increased by 26% and 58% for 1 units increase in BMI, and by 30% and 36% for 1 units increase in LSSF. Compared to subjects with persistent non-overweight from childhood to adulthood, subjects with overweight in childhood but non-overweight in adulthood had similar risks of high cfPWV (OR=1.59, 95%CI: 0.77-3.30)and high cIMT (OR=1.47, 95%CI:0.65-3.31). The risks of high cfPWV and high cIMT increased among subjects with non-overweight in childhood but overweight in adulthood (OR=1.92, 95%CI:1.37-2.68; OR=3.69, 95% CI:2.61- 5.23) and among subjects with persistent overweight from childhood to adulthood (OR=2.53, 95%CI:1.70-3.76; OR=5.37, 95%CI:3.62-7.97). CONCLUSIONS: We concluded that a overweight children changed to a healthy weight adult, the risks of adult subclinical atherosclerosis and arterial stiffness would not be increased.

[Change in the prevalence of obesity phenotypes and cardiometabolic disorders among children aged 6- 17 in Beijing during 2004- 2013].

OBJECTIVE: To examine the prevalence of obesity phenotypes and cardiometablic disorders (CDs) among children aged 6- 17 in Beijing from 2004 to 2013. METHODS: Data were obtained from two cross-section surveys, which were conducted in 2004 and 2013. In 2004, by using stratified cluster sampling design, 20 primary or middle schools were selected from 7 districts (Xicheng, Dongcheng, Chaoyang, Haidian, Daxing, Pinggu, and Yanqing) in Beijing, and 20 554 school children aged 6-17 were recruited, with weight, height, waist circumference and blood pressure measured. Fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were measured in 962 subjects from one school. In 2013, by using the same sampling design, 7 211 students from two districts (Haidian and Dongcheng) were surveyed with weight, height, waist circumference and blood pressure measured, and fasting plasma glucose and lipid profile (TC, TG, HDL-C, LDL-C) were measured for 1 344 subjects in the same school measured in 2004. Student's-t test was used to analyze the difference in body mass index(BMI), WC, and waist to height ratio (WHtR) among children between 2004 and 2010. Chi-square test was used to analyze the difference of hypertension, impaired fasting glucose(IFG), dyslipidemia, and metabolic disorders clustering between 2004 and 2010, and among different types of obesity; logistic regression model was used to analyze the association between three types of obesity and risks of cardiovascular metabolic disorders. RESULTS: In boys, BMI ((20.3 ± 4.4) vs (19.4 ± 4.2) kg/m(2), t=11.18, P<0.001), WC ((70.6 ± 12.8) vs (66.7 ± 11.8) cm, t=17.20, P<0.001) and WHtR (0.451 ± 0.064 vs 0.437 ± 0.059, t=11.64, P<0.001) were significantly higher in 2013 than those in 2004. Similarly in girls, BMI ((18.9 ± 3.6) vs (18.7 ± 3.7) kg/m(2), t=12.21, P<0.001), WC ((64.5 ± 9.6) vs (63.0 ± 9.3) cm, t=8.15, P<0.001) and WHtR (0.430 ± 0.047 vs 0.423 ± 0.047, t=14.13, P<0.001) were also significantly higher in 2013 than those in 2004. The prevalence of combined obesity rose from 8.27% (1 697/20 526) in 2004 to 10.74% (774/7 209) in 2013, and central obesity from 3.08% (632/20 526) to 4.44% (320/7 209). The prevalence of hypertension (10.78%(313/1 344) vs 4.29% (42/962), χ(2)=36.76, P<0.001), IFG(49.54%(664/1 344) vs 6.45%(63/962), χ(2)=506.61, P<0.001), high TC(11.53%(155/1 344) vs 5.03%(49/962), χ(2)=28.31, P< 0.001), high TG(7.51%(101/1 344) vs 3.59%(35/962), χ(2)=29.59, P<0.001) were significantly higher in 2013 than those in 2004. Subjects with combined obesity had higher risks of hypertension (OR=5.88, 95% CI: 4.42-7.82), high TG (OR=7.12, 95%CI: 4.35-11.64), low HDL-C (OR=3.04, 95%CI: 1.55-5.95), high LDL-C (OR=2.27, 95% CI: 1.22-4.02), CDs≥2 (OR=3.07, 95% CI: 2.09-4.50), comparing to children without obesity. CONCLUSION: The prevalence of types of obesity and obesity-related metabolic disorders, except for low HDL-C and high HDL-C, were significantly higher in 2013 than those 2004 among chlildren aged 6-17 year in Beijing. Children with combined obesity had higher prevalence of metabolic disorders.

Cardiovascular target organ damage could have been detected in sustained pediatric hypertension.

The aim of this study was to assess sustained hypertension in children and its impact on cardiovascular target organ damage (TOD). Blood pressure (BP) was measured in children in Beijing in 2009. Primary hypertension was diagnosed based on three separate visits. Hypertensive children and normotensive children were followed up in 2011. According to these evaluations, three groups were defined: sustained hypertension, non-sustained hypertension and normotensive. Cardiovascular TOD and metabolic disorders were evaluated using pulse-wave velocity (PWV), carotid intima-media thickness (cIMT), and assessments of left ventricular structure and kidney function. A total of 3032 children aged 9-15 years participated in this survey, of whom 128 were diagnosed with hypertension after three separate BP measurements. Eighty out of 128 (62.5%) hypertensive and 158 normotensive children were available for follow-up in 2011. Forty-eight children were defined as having sustained hypertension, 38 as non-sustained hypertension and 152 as normotensive. Mean levels of brachial-ankle PWV (baPWV), left ventricular mass, left ventricular mass index (LVMI) and cIMT were significantly different between the three groups (p < 0.01). Compared to normotensives, the odds ratios and 95% confidence intervals for elevated LVM and cIMT were 5.27 (1.57-17.66) and 2.88 (1.03-8.09) in the non-sustained hypertensive group, and 3.28 (1.00-10.74) and 7.25 (2.69-19.58) in the sustained hypertensive group. The children with sustained hypertension have the highest risk of developing arterial stiffness, left ventricular hypertrophy and early blood vessel endothelium damage. The indices of cIMT, LVMI and PWV were useful to identify children at high risk of cardiovascular TOD.

Role of intestinal flora in the development of nonalcoholic fatty liver disease in children.

In China, 45% of adolescents with obesity develop fatty liver disease, a condition that increases the long-term risk of developing cirrhosis and liver cancer. Although the factors triggering nonalcoholic fatty liver disease (NAFLD) vary in children, the composition of intestinal microflora has been found to play an increasingly important role. However, evidence is limited on the prevalence of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in Chinese children. Therefore, this study aimed to evaluate the fecal microbiome of Chinese children with NAFLD and further analyze the potential of flora in regulating NAFLD-related symptoms and metabolic functions. Specifically, the study applied a 16S rRNA and metagenomic sequencing to the fecal samples of pediatric patients with NAFLD, NASH, and NAFL, as well as healthy controls, to explore the correlation among NAFLD-related indexes, metabolic pathways, and gut flora. The findings showed that some fecal microbiota had a negative correlation with body mass index, and various NAFLD-related bacteria, including Lachnoclostridium, Escherichia-Shigella, and Faecalibacterium prausnitzii, were detected. Consequently, the study concluded that the variation in gut microbiota might be more important in improving NAFLD/NASH compared with single species, providing a microbiota diagnostic profile of NAFLD/NASH.IMPORTANCEThis study aims to characterize the gut microbiota in Chinese children with nonalcoholic fatty liver disease (NAFLD) through 16S rRNA and metagenomic sequencing. The results highlight the association between fecal microbiota and NAFLD in Chinese children, demonstrating distinct characteristics compared to adults and children from other countries. Based on the sequencing data from our cohort's fecal samples, we propose a microbiota model with a high area under the curve for distinguishing between NAFLD and healthy individuals. Furthermore, our follow-up study reveals that changes in the relative abundance of microbial biomarkers in this model are consistent with variations in patients' body mass index. These findings suggest the potential utility of the microbiota model and microbial biomarkers for diagnosing and treating NAFLD in children.

The life-course changes in muscle mass using dual-energy X-ray absorptiometry: The China BCL study and the US NHANES study.

BACKGROUND: Sarcopenia is an important indicator of ill health and is linked to increased mortality and a reduced quality of life. Age-associated muscle mass indices provide a critical tool to help understand the development of sarcopenia. This study aimed to develop sex- and age-specific percentiles for muscle mass indices in a Chinese population and to compare those indices with those from other ethnicities using the National Health and Nutrition Examination Survey (NHANES) data. METHODS: Whole-body and regional muscle mass was measured by dual-energy X-ray absorptiometry (DXA) in participants of the China Body Composition Life-course (BCL) study (17 203 healthy Chinese aged 3-60 years, male 48.9%) and NHANES (12 663 healthy Americans aged 8-59 years, male 50.4%). Age- and sex-specific percentile curves were generated for whole-body muscle mass and appendicular skeletal muscle mass using the Generalized Additive Model for Location Scale and Shape statistical method. RESULTS: Values of upper and lower muscle mass across ages had three periods: an increase from age 3 to a peak at age 25 in males (with the 5th and 95th values of 41.5 and 66.4 kg, respectively) and age 23 in females (with the 5th and 95th values of 28.4 and 45.1 kg, respectively), a plateau through midlife (30s-50s) and then a decline after their early 50s. The age at which muscle mass began to decline was 52 years in men with the 5th and 95th percentile values of 43.5 and 64.6 kg, and 51 years in women with the 5th and 95th percentile values of 31.6 and 46.9 kg. Appendicular skeletal muscle mass decreased earlier than whole body muscle mass, especially leg skeletal muscle mass, which decreased slightly after age 49 years in both sexes. In comparison with their US counterparts in the NHANES, the Chinese participants had lower muscle mass indices (all P < 0.001) and reached a muscle mass peak earlier with a lower muscle mass, with the exception of similar values compared with adult Mexican and White participants. The muscle mass growth rate of Chinese children decreased faster than that of other races after the age of 13. CONCLUSIONS: We present the sex- and age-specific percentiles for muscle mass and appendicular skeletal muscle mass by DXA in participants aged 3-60 from China and compare them with those of different ethnic groups in NHANES. The rich data characterize the trajectories of key muscle mass indices that may facilitate the clinical appraisal of muscle mass and improve the early diagnosis of sarcopenia in the Chinese population.

Clinical characteristics of adolescent-onset gout in Chinese: A hospital-based cross-sectional study.

OBJECTIVE: Adolescent-onset gout has a greater impact on the lives and health of patients than adult-onset gout. However, there is a relative lack of clinical information on adolescent-onset gout. Hence, we analyzed a Chinese cohort. METHODS: We studied clinical features of 9,003 Chinese patients. Gout onset age of 12 - 19 years is defined as adolescent-onset group (AG), 20 - 40 years as early-onset group (EG), and 41 - 64 years as late-onset group (LG). Multivariable regression analysis evaluated factors associated with recurrent flares, serum urate (SU) levels, and underexcretion type in AG. RESULTS: Compared with EG and LG, the AG had higher SU levels [AG: 9.5 (2.2) mg/dL, EG: 8.6 (2.1) mg/dL, LG: 7.73 (2.0) mg/dL, P < 0.001], higher percentage of positive family history of gout (AG: 41.8 %, EG: 29.6 %, LG: 24.6 %, P < 0.001), underexcretion type (AG: 62.4 %, EG: 62.5 %, LG: 58.8 %, P = 0.04), recurrent flares (AG: 78.1 %, EG: 70.3 %, LG: 68.9 %, P = 0.01). Urate-lowering therapy (ULT) initiated [OR 6.58 (95 % CI 1.35 - 32.00)] and hypercholesterolemia [OR 4.16 (95 % CI 1.28 - 13.53)] were associated with recurrent flares. eGFR was identified to be a significant variable of increasing SU levels [beta -0.24 (95 % CI -0.04 to -0.01)]. Hypertriglyceridemia [OR 0.35 (95 % CI 0.17 - 0.71)] was related to underexcretion type. CONCLUSION: Adolescent-onset gout patients had clinically distinctive features with higher SU levels, BMI, positive gout family history, underexcretion type and recurrent flares. These specific populations were less likely to achieve ULT target, requiring more clinical attention.

Prevalence and risk factors of hypertension based on repeated measurements in Chinese children and adolescents.

OBJECTIVES: This study aimed to determine the prevalence of hypertension from repeated blood pressure (BP) measurements, and examine the association between hypertension and obesity, as well as other related risk factors, in a Chinese pediatric population. METHODS: A total of 6692 children, aged 3-18 years, were recruited in 2010. Anthropometric measurements and BP were measured using a mercury sphygmomanometer. Those with an elevated BP were screened a second or third time at 2-week intervals. "Hypertension" was defined as elevated BP on all three occasions. A self-administered questionnaire was completed. RESULTS: The prevalence of an elevated BP was 18.2%, 5.1% and 3.1% on the first, second and third visits, respectively. The odds ratios (ORs) and 95% confidence intervals (CIs) for an elevated BP among obese children were 7.07 (5.94-8.42), 17.23 (12.63-23.52) and 20.63 (13.69-31.09), and among those with a paternal history of hypertension were 1.26 (0.98-1.61), 1.35 (0.90-2.02) and 1.80 (1.15-2.81) on each consecutive visit. CONCLUSIONS: Repeated measurements are required to confirm the diagnosis of hypertension in children and that obesity and paternal hypertension are strongly associated with pediatric hypertension.

BMI at different childhood age periods associated with cardiometabolic disorders in young adulthood.

OBJECTIVE: The aim of this study was to investigate when the association between childhood obesity and adult cardiometabolic disorders starts to be operative. METHODS: The study cohort included 811 participants who had data on blood pressure, lipid profile, fasting blood glucose, fasting insulin, or alanine aminotransferase in adulthood and had at least one measurement of BMI in childhood. RESULTS: Childhood BMI z score was significantly associated with increased risks of ≥1 cardiometabolic disorders, ≥2 cardiometabolic disorders, and elevated blood pressure in adulthood for age groups of 6 to 9 years, 10 to 12 years, 13 to 15 years, and 16 to 18 years, after adjustment for covariates. For low high-density lipoprotein cholesterol, significant associations were observed for age groups of 10 to 12 years, 13 to 15 years, and 16 to 18 years. For elevated triglyceride and elevated alanine aminotransferase, significant associations were observed for age groups of 13 to 15 years and 16 to 18 years. For insulin resistance, significant associations were observed for age groups of 10 to 12 years and 16 to 18 years. For elevated total cholesterol, elevated low-density lipoprotein cholesterol, or elevated fasting blood glucose, no association was observed in any age group. CONCLUSIONS: The association between childhood BMI and adult cardiometabolic disorders begins to be operative from early life. These results support universal screening of childhood obesity starting at an early age.

Overfat cutoffs and the optimal combination of body fat indices for detecting cardiometabolic risk among school-aged children.

OBJECTIVE: This study aimed to develop cutoffs and the optimal combination for body fat indices for screening cardiometabolic risk (CMR) among the pediatric population. METHODS: This cross-sectional study consisted of 8710 (50.3% boys) Chinese children aged 6 to 18 years. Body fat indices, including fat mass index (FMI), body fat percentage, trunk to leg fat ratio (TLR), and android to gynoid fat ratio, were derived from dual-energy x-ray absorptiometry scans. The area under the receiver operating characteristic curve was used to determine the best combination and optimal cutoffs of body fat indices to identify CMR. RESULTS: Compared with anthropometry-based obesity measures, i.e., BMI and waist circumference, the FMI + TLR combination presented statistically higher area under the receiver operating characteristic curve values for discriminating CMR and its clustering. The optimal overfat cutoffs of FMI and TLR were respectively determined at the 75th percentile in boys and at the 80th percentile of FMI and the 75th percentile of TLR in girls. Moreover, simplified thresholds derived from age-group-merged cutoffs showed similar performance as optimal cutoffs in detecting CMR. CONCLUSIONS: Both the optimal and simplified overfat cutoffs were provided for the Chinese pediatric population. The use of FMI and TLR together allows for adequate screening of CMR and its clustering.