Obesity in adolescence is associated with significant morbidity and predisposes adolescents to the development of cardiovascular disease (CVD). Although a number of traditional CVD risk factors have been identified in youth, limited data exist regarding non-traditional CVD risk factors. In 89 adolescents with metabolic syndrome (MetS), with 60 age-, gender-, and BMI-matched controls, we determined the non-traditional CVD risk factors (hs-CRP, TG/HDL ratio, ApoB/ApoA1 ratio, NAFLD) in order to investigate whether they may be used as biomarkers for predicting future CVD, and we evaluated their response to the implementation of a multidisciplinary, personalized, lifestyle intervention program for 1 year. We demonstrated that the TG/HDL ratio, IL-2, IL-6, IL-17A, and INF-γ were significantly increased in subjects with MetS than in controls, and may be used as biomarkers to predict future CVD. Subjects with MetS had an increased mean carotid intima-media thickness (cIMT) and prevalence of NAFLD than the controls, while the prevalence of NAFLD correlated strongly with cIMT and IL-6 concentrations. Most of the non-traditional cardiovascular risk factors improved following the implementation of a lifestyle intervention program. These findings indicate that adolescents with MetS may have a greater risk for developing atherosclerosis early in life, while early lifestyle intervention is crucial for preventing the arteriosclerotic process in youth.

Background: Obesity in childhood and adolescence represents a major public health problem, mostly attributed to dietary and physical activity factors. We aimed to determine the dietary and physical activity habits of participants before and after the implementation of a personalized, multidisciplinary, lifestyle intervention program for the management of obesity in the context of the Horizon Research Project ‘BigO: Big Data against Childhood Obesity’. Methods: Three hundred and eighty-six (n = 386) children and adolescents (mean age ± SD: 12.495 ± 1.988 years, 199 males and 187 females) participated in the study prospectively. Based on body mass index (BMI), subjects were classified as having obesity (n = 293, 75.9%) and overweight (n = 93, 24.1%) according to the International Obesity Task Force (IOTF) cut-off points. We implemented a personalized, multidisciplinary, lifestyle intervention program providing guidance on diet, sleep, and exercise, and utilized the BigO technology platform to objectively record data collected via a Smartphone and Smartwatch for each patient. Results: Following the intervention, a statistically significant decrease was noted in the consumption of cheese, cereal with added sugar, savory snacks, pasta, and fried potatoes across both BMI categories. Also, there was an increase in daily water intake between meals among all participants (p = 0.001) and a reduction in the consumption of evening snack or dinner while watching television (p < 0.05). Boys showed a decrease in the consumption of savory snacks, fried potato products, and pasta (p < 0.05), an increase in the consumption of sugar-free breakfast cereal (p < 0.05), and drank more water between meals daily (p < 0.001). Conclusions: Our findings suggest that a personalized, multidisciplinary, lifestyle intervention improves the dietary habits of children and adolescents.

Thyroid hormones regulate metabolism and have a major impact in maintaining cardiovascular homeostasis. The purpose of our study was to examine the relation of thyrotropin (TSH) and thyroid hormones with cardiometabolic parameters in children and adolescents with obesity, overweight, and normal body mass index (BMI) before and after the implementation of a comprehensive, multidisciplinary, personalized, lifestyle intervention program for 1 year. One thousand three hundred and eleven (n = 1311) children and adolescents aged 2 to 18 years (mean age ± SD: 10.10 ± 2.92 years) were studied prospectively. Patients were categorized as having obesity (n = 727, 55.45%), overweight (n = 384, 29.29%) or normal BMI (n = 200, 15.26%) according to the International Obesity Task Force (IOTF) cutoff points. All patients received personalized guidance on diet, sleep, and physical activity at regular intervals throughout the 1-year period. Detailed clinical evaluation and hematologic, biochemical and endocrinologic investigations were performed at the beginning and the end of the study. Subjects with obesity had a more adverse cardiometabolic risk profile than subjects with overweight and normal BMI on both assessments. At initial evaluation, total T3 concentrations were positively associated with uric acid and HbA1C, and free T4 concentrations were negatively associated with insulin concentrations, while there was no association between TSH concentrations and cardiometabolic risk parameters. Following the 1 year of the multidisciplinary, lifestyle intervention program, the concentrations of lipids, HbA1C, ALT, and γGT improved significantly in all subjects. Changes in TSH concentrations were positively associated with changes in systolic blood pressure (SBP), glucose, triglycerides, and cholesterol concentrations. Changes in free T4 concentrations were negatively associated with changes in cholesterol and insulin concentrations. Furthermore, changes in T3 concentrations were positively associated with changes in HbA1C, glucose, uric acid, and triglyceride concentrations. These findings indicate that in children and adolescents with overweight and obesity, thyroid hormones are associated with indices conferring cardiometabolic risk.

Background/Objectives: Childhood obesity is one of the most challenging contemporary public health problems. Children and adolescents with obesity experience multiple psychosocial difficulties, such as low self-esteem, depression, anxiety, and behavioral problems, which persist for a long time. The aim of the study was to assess the effect of a multidisciplinary personalized lifestyle intervention for depressive and anxiety symptoms, as evaluated by psychometric questionnaires, and their effect and association with cardiometabolic parameters in children and adolescents with overweight and obesity before and after the intervention. Methods: Six hundred and eleven (n = 611) children and adolescents (mean age ± SE: 10.39 ± 0.10 years; 51.5% females, 46.6% pubertal) were studied prospectively. Subjects were classified as being obese (50.2%), overweight (33.5%), or having a normal BMI (16.2%) according to IOTF criteria. All participants entered a 1-year lifestyle intervention program; laboratory investigations were obtained at the beginning and end of the study and two psychometric questionnaires were completed, the CDI and SCARED, which evaluate symptoms of depression and anxiety, respectively. Results: Following the lifestyle intervention, a significant decrease was noted in anxiety scores in all subjects and in depression scores in youth with obesity, as well as in adolescents with obesity, while females displayed a reduced response to the intervention. Insulin resistance and metabolic syndrome parameters, cortisol, PRL, and LH concentrations were positive predictors for depressive and anxiety symptoms. Conclusions: The implementation of a multidisciplinary personalized lifestyle intervention program in the management of childhood obesity is associated with a significant decrease in cardiometabolic and psychosocial comorbidities in children with and without excess adiposity. The improvement in mental health is likely mediated by an improvement in energy metabolism with subsequent improvement in neuroinflammation owing to lifestyle changes.

Background: The underlying biological mechanisms linking blood pressure (BP) and cardiovascular diseases (CVD) are only partly understood. We aimed to identify metabolic signatures associated with systolic and diastolic BP and investigate their subsequent association with risk of CVD. Methods and Results: The study included 201 742 UK Biobank participants with measurements on 249 metabolic biomarkers. A multistep adaptive elastic net penalized regression with 10‐fold cross‐validation was employed to identify metabolic signatures for systolic BP and diastolic BP. External validation was conducted on 848 participants from the EHS (Epirus Health Study). We further assessed the associations between BP metabolic signatures and incident composite CVD (N=6742), myocardial infarction (N=4192), and stroke (N=2757) in the UK Biobank, using multivariable Cox regression models. The metabolic signatures comprised 31 and 25 metabolites, robustly correlated with systolic BP and diastolic BP, respectively, in both the UK Biobank and the EHS. Following adjustments (including BP), the metabolic signature for systolic BP was positively associated with incident myocardial infarction (hazard ratio [HR], 1.11 [95% CI, 1.07–1.15]) and CVD (HR, 1.07 [95% CI, 1.04–1.10]). Similarly, the metabolic signature for diastolic BP was associated with a higher risk of myocardial infarction (HR, 1.16 [95% CI, 1.12–1.20]) and CVD (HR, 1.09 [95% CI, 1.05–1.12]). The associations between the signatures and stroke were not significant. The metabolic signatures partly mediated the total effect of the BP traits on the risk of myocardial infarction and CVD. Conclusions: Our findings may enhance our understanding of the biological mechanisms through which BP affects CVD.

Background/Objective: Secreted frizzled-related protein 5 (Sfrp5) is an anti-inflammatory adipokine that has been implicated in the pathophysiology of obesity and its metabolic complications. Despite the fact that numerous studies have been carried out in adults, limited data on Sfrp5 exist for youth, especially in relation to overweight and obesity. Methods: In our study, we assessed the concentrations of Sfrp5, total oxidative (TOS) and antioxidative (TAS) status, high-sensitivity C-reactive protein (hs-CRP), and several cytokines (IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-12, TNF-α) in 120 children and adolescents (mean age ± SE: 11.48 ± 0.25 years; 48 prepubertal, 72 pubertal; 74 males and 46 females) before and 1 year after the implementation of a personalized, structured, lifestyle intervention program of healthy diet, sleep, and physical exercise. Results: Based on the body mass index (BMI), participants were categorized as having morbid obesity (n = 63, 52.5%), obesity (n = 21, 17.5%), overweight (n = 22, 18.33%), or normal BMIs (n = 14, 11.67%), based on the International Obesity Task Force (IOTF) cut-off points. Following the 1-year lifestyle intervention program, a significant improvement in anthropometric measurements (BMI, BMI-z score, diastolic blood pressure, WHR, and WHtR), body-composition parameters, hepatic enzymes, lipid profile, inflammation markers, and the insulin-sensitivity profile (HbA1C, HOMA index) was observed in all subjects. Sfrp5 decreased in subjects with obesity (p < 0.01); however, it increased significantly (p < 0.05) in patients with morbid obesity. Linear regression analysis indicates that TNF-α and systolic blood pressure were the best positive predictors and hs-CRP was the best negative predictor for Sfpr5 concentration at initial assessment and glucose concentration for ΔSfrp5, while TNF-α and TAS were the best positive predictors for Sfpr5 concentration at annual assessment. Conclusions: These results indicate that Sfrp5 is associated with severe obesity and is increased following weight loss in children and adolescents with morbid obesity. It is also related to metabolic homeostasis, as well as inflammation and oxidative status.