Effects Of Interaction Between Genetic And Environmental Factors On Obesity And Metabolic Abnormalities In Children And Adolescents

[Background]The alarming increase in prevalence of childhood obesity and its related cardio-metabolic disorders such as cardiovascular disease (CVD), Type 2 diabetes mellitus (T2DM) have become a global health problem. And the childhood obesity and metabolic disorder is more likely to continuous to adulthood. Obesity and metabolic disorders are influenced by genetic and environmental factors which can be intervened to improve the status of obesity and metabolic disorders.Recent studies demonstrate that not all obese individuals have metabolic complications, which was recognized as metabolically healthy obesity (MHO). At present, no study has yet investigated the contribution of both genetic and environmental factors to the pathogenesis of obesity subtype.[Objective](1) To assess the influence of lifestyle behaviors and social-economic factors on obesity and metabolic disorder among children aged 6-18 in Beijing, China and their self-awareness.(2) To assess the association of sleep duration with adipokine levels and cardio-metabolic risk factors, and to explore the possible mediating roles of adipokines, in a cohort of Chinese school-aged children.(3) To determine the prevalence of MHO in Chinese children and to investigate environmental and genetic factors impacting on MHO status.[Methods]We conducted a cross-sectional study consisted of 3250 children aged 6-18 years old from Beijing children and adolescents metabolic syndrome study (BCAMS) in 2004. Age-and sex-specific BMI percentiles, developed by the Working Group for Obesity in China, were used to define overweight (85th) and obesity (95th). Metabolic Syndrom (MS) was diagnosed using a modified Adult Treatment Panel III (ATP III). Homeostasis model of assessment-insulin resistance (HOMA-IR) was used to access insulin resistance (IR). We applied two commonly used definitions including cardio-metabolic risk factors (CR) and IR to classify MHO. Self-reported information on lifestyle and social-economic factors were collected by questionnaire. Single nucleotide polymorphisms (SNPs) were genetyped by mass-spectrography. Serum adipokines and insulin were measured by enzyme-linked immunosorbent assay (ELISA). Anthropometric measurements included high, weigh, waist circumference (WC), fat mass percentage (FAT%) and blood pressure. Blood samples were analyzed for concentrations of fasting blood-glucose (FBG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C). Comparisons were made among groups using t test or analysis of variance (ANOVA) or chi-square test. Multivariate logistic regression analysis and multiple linear regression analysis were performed to multivariate analysis.[Results](1) The influence of lifestyle behaviors and social-economic factors on obesity and metabolic disorder among children aged 6-18 and their self-awareness:①Environmental factors and obesity:Long time (> 2 hours/day) to watch TV were independent risk factors for obesity and more frequency of breakfast, moderate-to-vigorous physical activity (MVPA), walking to school, higher father’s education, employed father, family income> 5000 yuan per month and adequate sleep were independent protect factors for obesity. Frequency of breakfast, family monthly income, physical activity, walking to school, mother’s education, employed parents and sleep duration were independently negative with BMI and wathching TV and mother’s education were independently positive with BMI. Frequency of breakfast, physical activity, walking to school, sleep duration, employed parents and family monthly income were independently negative with LEP and mother’s education were independently positive with LEP. Frequency of soft drink were independently negative with APN and walking to school and employed mother were independently positive with APN.②Environmental factors and metabolic disorder:Long time to watch TV were independent risk factors for MS and walking to school, employed father and family income> 5000 yuan per month were independent protect factors for MS. Frequency of breakfast, physical activity, walking to school, employed father and family mothly income were independently negative with FBG and frequency of dairy and frequency of soft drink were independently negative with FBG. Physical activity, walking to school, employed father and family mothly income were independently negative with IR and frequency of soft drink and mother’s education were independently positive with IR. Frequency of vegetable and walking to school were independently negative with TC and frequency of sea-food and meat were independently positive with TC. Physical activity, employed father and family monthly income were independently negative with TG. Frequency of fruit, frequency of dairy, frequency of sea-food, physical activity, walking to school were independently positive with HDL-C. Frequency of vegetale and walking to school were independently negative with LDL-C and frequency of sea-food was independently positive with LDL-C. Frequency of dairy, frequency of fruit, walking to school, father’s education, employed father and family monthy income were independently negative with systolic blood pressure (SBP) and watching TV were independently positive with SBP. Walking to school, mother’s education and family monthy income were independently negative with diastolic blood pressure (DBP).③Self-awareness:10.2% of the normal weight children recognized themselves as leaner, in which 69.7% children reported that they would increase their body weight.15.8% of the overweight children recognized themselves as normal weight, in which 60.2% overweight children reported that they would keep their body weight, 22.4% overweight children reported that they would not take measures to decrease their body weight, and even 2.0% overweight children reported that they would increase their body weight. There were 0.2% obesity children recognized themselves as normal weight, in which there wew 7.1%,57.1% and 17.9% children reported that they would increase their body weight, keep their body weight and not take measures to decrease their body weight, respectively. There were 52.2% obesity children recognized themselves as a bit heavy, in which there wew 0.7%,12.1% and 18.2% children reported that they would increase their body weight, keep their body weight and not take measures to decrease their body weight, respectively. There were 45.2% obesity children recognized themselves as very heavy, even in which there were 2.7% and 13.4% children reported that they would keep their body weight and not take measures to decrease their body weight, respectively.(2) The association of sleep duration with adipokine levels and cardio-metabolic risk factors, and the mediating roles of adipokines:Among the 6-12 years old children, after adjusting for covariates, short sleep duration was associated with higher leptin, Fibroblast growth factor 21 (FGF21), and lower High molecular weight adiponectin (HMW-APN); the association with leptin remained significant even further adjustment of BMI. As expected, short sleep duration was associated with increased BMI, WC, FBG, insulin, HOMA-IR, TG, and lower HDL-C. However, the significance of these associations, except for FBG, disappeared after further adjustment of leptin. For the 13-18 years old group, short sleep duration was associated with higher Retinol binding protein 4 (RBP4), BMI, WC and FAT%.(3) The prevalence of MHO in Chinese children and the influence of environmental and genetic factors impacting on MHO status:The prevalence of MHO-IR and MHO-CR were 27.1% and 37.2%, respectively. WC was an independent predictor of MHO regardless of definitions, whereas walking to school and KCNQ1-rs2237897 were independent predictors of MHO-CR. Acanthosis nigricans, birth weight, the frequency of soft drinks consumption, mother’s education status and KCNQ1-rs2237892 were independent predictors of MHO-IR. Multiplicative interaction effects were found between KCNQ1-rs2237897 and walking to school on MHO-CR and between rs2237892 and consumption of soft drinks on MHO-IR.[Conclusions](1) The interaction between genetic factors and environmental factors lead to obesity and metabolic disorder among children. Obesity children had a poor recognition on their weight, which could aggravate the status of obesity and metabolic disorder in children.(2) Short sleep duration is strongly associated with obesity along with adverse adipokine secretion pattern among Chinese children. The associations with cardio-metabolic risk factors appear to be more remarkable exclusively in younger children, and could be at least partly explained by leptin.(3) Approximate one-third of Chinese obese children can be classified as MHO. Both genetic predisposition and environment factors and their interaction contribute to the prediction of MHO status.