Approach to the Treatment of Children and Adolescents with Obesity.

Pediatric obesity continues to be an omnipresent disease; 1 in 5 children and adolescents have obesity in the United States. The comorbidities associated with youth-onset obesity tend to have a more severe disease progression in youth compared to their adult counterparts with the same obesity-related condition. A comorbidity of focus in this study is metabolism-associated steatotic liver disease (MASLD), which has rapidly evolved into the most common liver disease seen in the pediatric population. A direct association exists between the treatment of MASLD and the treatment of pediatric obesity. The current evidence supports that obesity treatment is safe and effective.

Increased serum carboxylesterase-1 levels are associated with metabolic dysfunction associated steatotic liver disease and metabolic syndrome in children with obesity.

BACKGROUND: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. METHODS: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. RESULTS: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. CONCLUSIONS: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity.

Application of transumbilical single-incision laparoscopy in the treatment of complicated appendicitis in overweight/obese adolescents.

OBJECTIVE: To investigate the clinical efficacy of transumbilical single-incision laparoscopic surgery in the treatment of complicated appendicitis in overweight/obese adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 226 adolescent patients with complicated appendicitis who were admitted to our hospital from January 2014 to June 2022. Among them, 102 cases underwent transumbilical single-incision laparoscopic appendectomy as the observation group, and another 124 cases underwent conventional three-port laparoscopic appendectomy as the control group. The surgical time, intraoperative blood loss, duration of incisional pain, postoperative flatus time, length of hospital stay, surgical site infection (SSI), satisfaction with cosmetic result, and occurrence of postoperative complications were compared between the two groups. RESULTS: Both groups completed the surgery smoothly, and there were no statistically significant differences in gender, age, BMI, duration of illness, white blood cell count, and preoperative CRP value between the two groups (P > 0.05). There were no statistically significant differences in surgical time and intraoperative blood loss between the two groups (P > 0.05). However, the observation group had shorter hospital stays, shorter duration of incisional pain, shorter postoperative time to flatus, and lower overall postoperative complication rates compared to the control group, with statistically significant differences (P < 0.05). The observation group had higher satisfaction with cosmetic result compared to the control group, with statistically significant differences (P < 0.05). Both groups were followed up for one year postoperatively, and there were no occurrences of residual appendicitis or severe adhesive intestinal obstruction. CONCLUSION: When proficiently mastered, the application of transumbilical single-incision laparoscopy in the treatment of complicated appendicitis in overweight/obese adolescents offers advantages such as minimal trauma, rapid recovery, fewer complications, and improved aesthetic outcomes.

Childhood Cardiovascular Health, Obesity, and Some Related Disorders: Insights into Chronic Inflammation and Oxidative Stress.

Childhood obesity and associated metabolic abnormalities have become pressing public health concerns worldwide, significantly impacting cardiovascular health. Metabolic syndrome, characterized by a cluster of metabolic abnormalities including central obesity, altered glucose metabolism, dyslipidemia, and arterial hypertension, has emerged as a critical precursor to cardiovascular disease. Chronic systemic inflammation and oxidative stress seem to play pivotal roles in the pathogenesis of childhood obesity-related disorders such as early atherosclerosis. A significant distinction between the objective components of cardiovascular health metrics, including body mass index, blood pressure, cholesterol, and fasting glucose levels, and the definition of metabolic syndrome is evident in the identification of obesity. Whereas cardiovascular health metrics predominantly rely on body mass index percentiles to assess obesity, metabolic syndrome criteria prioritize waist circumference, specifically targeting individuals with a measurement ≥90th percentile. This discrepancy emphasizes the need for a nuanced approach in assessing the risks associated with obesity and underscores the importance of considering multiple factors when evaluating cardiovascular risk in children. By recognizing the complex interplay between various health metrics, obesity and metabolic syndrome criteria, clinicians can more accurately identify individuals at risk and tailor interventions accordingly to mitigate cardiovascular disease in children with obesity.

The phenotype of the pediatric patient with Cushing syndrome but without obesity.

OBJECTIVE: Cushing syndrome (CS) often presents with obesity that is not as severe in children as it is in adults. The role of obesity in the severity of metabolic syndrome in children with CS has not been studied. This study evaluates whether pediatric patients with CS have obesity-specific differences in their demographic, biochemical, and presenting findings. DESIGN: Cohort study. PARTICIPANTS AND METHODS: We analyzed 273 patients with young onset of CS at ≤18 years old and who were classified as patients with or without obesity based on their BMI z scores. RESULTS: Patients without obesity (n = 84, 31%) were more frequently females with an older age of onset compared with patients with obesity (n = 189, 69%). Consistent with their older age, patients without obesity were also more likely to have advanced Tanner stages. Patients with and without obesity had a similar duration of disease, but patients with obesity showed higher markers of hypercortisolemia (urinary free cortisol, UFC). A higher prevalence of hypertension and insulin resistance was seen in patients with obesity than those without obesity, adjusting for UFC (P < .05 for all comparisons). While fatty liver disease was not statistically different among the entire cohort, elevated alanine transaminase and metabolic dysfunction-associated steatotic liver disease scores were more common in ACTH-dependent CS patients with obesity (P < .05). CONCLUSIONS: Weight gain appears to mediate some but not all the cortisol-associated complications in pediatric CS. Therefore, obesity may be a modifiable risk factor among these patients.

Converging Pathways between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Diabetes in Children.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM, where each condition influences and exacerbates the progression of the other. This review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment into the diagnostic arsenal for children showing insufficient glycemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

Overview of Pediatric Obesity as a Disease.

The authors highlight well-known and hypothesized pathophysiologic mechanistic links underlying obesity and the various pediatric disorders across multiple organ systems with which it is associated. Obesity is attributed to an imbalance in energy intake versus expenditure; there is growing knowledge regarding its multifactorial origins, dysfunctional physiologic processes, and adverse health consequences. Individuals with obesity exhibit variations in metabolic rate, genetic predisposition, and hormonal regulation, influencing diverse responses in regulating energy balance. Understanding the complex mechanistic relationships surrounding the pathophysiology of obesity assists in its consideration as a disease process, allowing pediatric health practitioners to manage its sequelae more effectively.

Disordered Eating in Pediatric Obesity.

Children and youth with overweight and obesity are at an increased risk for the development of an eating disorder. Previous research has shown that disordered eating behaviors are prevalent in this population. Screening for disordered eating behaviors in children and youth with overweight and obesity is necessary to determine the course of the treatment. In children and youth with obesity and comorbid disordered eating behaviors, treatment should be multidisciplinary and include psychological, medical, nutrition, and physical activity care.

Reduced insulin clearance in paediatric metabolic (dysfunction)-associated fatty liver disease and its dual role in beta-cell offload and diabetes risk.

AIM: Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)-associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and ß-cell function in obese Chinese children with MAFLD. METHODS: In total, 204 obese children (74 MAFLD) aged 4-17 years were enrolled into this study. HIC, insulin sensitivity and ß-cell function were calculated using the oral glucose tolerance test (1.75 g/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product-moment correlation coefficients. HIC and glucose homeostasis were assessed in a high-fat diet mouse model, and liver samples were collected for molecular analysis. RESULTS: Obese children with MAFLD exhibited significantly lower HIC (AUCC-peptide/insulin ratio, p = 0.0019), higher insulin resistance (homeostatic model assessment of insulin resistance, p = 0.002), and increased compensatory ß-cell function (homeostatic model assessment-ß, p = 0.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (r = -0.5035, p < 0.0001) and ß-cell function (r = -0.4576, p < 0.0001). However, pancreatic ß-cell dysfunction (p = 0.046) was accompanied by future reduced HIC (p = 0.034) in children with MAFLD in prediabetes. In a high-fat diet mouse model, MAFLD mice showed a 50% reduction in insulin-degrading enzyme expression, consistent with the observed decrease in HIC. CONCLUSIONS: A lower HIC may offload pancreatic ß-cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized.

Associations of Obstructive Sleep Apnea Risk with Obesity, Body Composition and Metabolic Abnormalities in School-Aged Children and Adolescents.

The objective of this study is to explore the associations between obesity, body composition, and the self-reported risk of obstructive sleep apnea (OSA) and to examine whether the risk of OSA is related to metabolic abnormalities in children and adolescents aged 6-17 years. Utilizing data from the 2022 to 2023 Beijing Children and Adolescents Health Cohort baseline survey, 5000 school-aged participants were analyzed. OSA risk was assessed via the Pediatric Sleep Questionnaire, with anthropometric and body composition measurements taken. Metabolic markers included blood pressure, lipid levels, blood glucose, and uric acid. Associations were analyzed using logistic regression and generalized linear models. Results showed that 88.6% were low-risk and 11.4% were high-risk for OSA. Overweight (aOR 1.53, 95% CI 1.22-1.92), obesity (aOR 1.94, 95% CI 1.57-2.40), and abdominal obesity (aOR 1.59, 95% CI 1.31-1.93) significantly increased OSA risk. High fat mass was a critical factor, while muscle mass was not, especially in those who were overweight and obese. Associations of OSA risk with metabolic abnormalities were non-significant after adjusting for BMI. Our research highlights the significant associations of obesity and body composition with OSA risk, with child BMI influencing the relationship between OSA and metabolic abnormalities. Future research should explore causative relationships and the enduring impacts of OSA on metabolic health in children.

Non-Pharmacological Treatment for Cardiovascular Risk Prevention in Children and Adolescents with Obesity.

In younger generations, excess weight has reached very alarming levels. Excess weight in adults is associated with increased mortality and morbidity from cardiovascular disease. However, it is not easy to distinguish to what extent these effects are the result of obesity itself or how much is due to the various cardiovascular risk factors that often accompany excess weight. Several risk factors, such as hypertension, dyslipidemia, hyperuricemia, glucose intolerance, and type 2 diabetes mellitus, are already present in pediatric age. Therefore, early intervention with the goal of correcting and/or eliminating them is particularly important. In the child and adolescent with obesity, the first approach to achieve weight reduction and correct the risk factors associated with severe excess weight should always be non-pharmacologic and based on changing poor eating habits and unhealthy lifestyles. The purpose of this review is to give an update on non-pharmacological interventions to be implemented for cardiovascular prevention in children and adolescents with obesity, and their effectiveness. In particular, interventions targeting each individual cardiovascular risk factor will be discussed.

Obesity-Related Complications Including Dysglycemia Based on 1-h Post-Load Plasma Glucose in Children and Adolescents Screened before and after COVID-19 Pandemic.

Childhood obesity, with its metabolic complications, is a problem of public health. The International Diabetes Federation (IDF) has recommended glucose levels 1 h post oral glucose load (1h-PG) > 155-209 mg/dL as diagnostic for intermediate hyperglycemia (IH), while >209 mg/dL for type 2 diabetes (T2D). The aim of the study was to assess the occurrence of prediabetes, IH, and T2D in children and adolescents with simple obesity according to the criteria of American Diabetes Association (ADA) and of IDF, and the effect of COVID-19 pandemic on these disorders. Analysis included 263 children with simple obesity, screened either in prepandemic (PRE-113 cases) or post-pandemic period (POST-150 cases). All children underwent 2 h OGTT with measurements of glucose and insulin every 0.5 h, lipid profile, and other tests; indices if insulin resistance (IR): HOMA, QUICKI, Matsuda index, AUC (glu/ins) were calculated. The incidence of T2D, prediabetes, and IH was higher in POST with respect to PRE, with significant differences in the indices of IR, except for HOMA. Significant differences were observed in the assessed parameters of glucose metabolism among the groups with T2D, prediabetes, IH, and normal glucose tolerance (NGT), with some similarities between IH (based on 1h-PG) and prediabetes. Increased frequency of dysglycemia among children and adolescents with simple obesity is observed after COVID-19 pandemic. Metabolic profile of patients with IH at 1h-PG is "intermediate" between NGT and prediabetes.

The relationship between body mass index and cerebrospinal fluid pressure in children with pseudotumor cerebri.

BACKGROUND: Childhood obesity has become a major global health problem. Obesity is associated with major health problems, such as diabetes, hypertension, dyslipidemia, cardiovascular disease. Obesity is also considered a risk factor for Pseudotumor cerebri (PTC). The present study aimed to investigate the relationship between body mass index (BMI), and cerebrospinal fluid (CSF) pressure in patients with pseudotumor cerebri. METHODS: A total of 48 children diagnosed with PTC, who were aged < 18 years and followed up in the pediatric clinic were included in the retrospective study. National BMI percentile curves were used for reference. We investigated statistically the relationship between BMI, clinical and laboratory results, and CSF pressure in patients. RESULTS: Of total patients 27 were female (56.25%) and 21 were male (43.75%). With regard to the BMI percentile, 20 (41.67%) were overweight or obese. CSF pressure was higher in overweight and obese patients compared to children with BMI in normal ranges (p < 0.05). A statistically significant positive correlation was also observed between BMI and CSF pressure values and between monocyte and CSF values (p < 0.05). CONCLUSIONS: The results of the present study indicate a direct relationship between CSF pressure and BMI in children with PTC. Appropriate diet, exercise, and medical treatment in overweight and obese children can make a significant contribution to the treatment of PTC. Additionally, a significant correlation was observed between CSF pressure and monocyte levels.

Assessing the efficacy of tocotrienol-rich fraction vitamin E in obese children with non-alcoholic fatty liver disease: a single-blind, randomized clinical trial.

BACKGROUND: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. TRIAL REGISTRATION: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

Monocyte to High-density Lipoprotein Cholesterol Ratio as a Predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity.

OBJECTIVE: Inflammation is involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a marker for various inflammation-related diseases. The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity. METHODS: Based on hepatic ultrasound, a total of 504 children with obesity (357 with NAFLD and 147 without NAFLD) were included in the study. The correlation between the MHR and NAFLD risk factors was assessed by Pearson's and Spearman's analyses. Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD. RESULTS: The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD [0.52 (0.44-0.67) versus 0.44 (0.34-0.57), P<0.001]. Multivariate stepwise logistic regression analysis demonstrated that the MHR [odds ratio (OR): 1.033, 95% confidence interval (CI): 1.015-1.051; P<0.001] was an independent predictor of NAFLD in childhood obesity patients, as were age (OR: 1.205, 95% CI: 1.059-1.371; P=0.005], waist circumference [OR: 1.037, 95% CI: 1.008-1.067; P=0.012], and alanine transaminase [OR: 1.067, 95% CI: 1.045-1.089; P<0.001]. Additionally, MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors. CONCLUSION: The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

Childhood obesity in relation to risk of dental caries: a cumulative and dose-response systematic review and meta-analysis.

INTRODUCTION: Earlier studies reported inconsistent findings for the association of childhood obesity with the risk of dental caries. In this systematic review and meta-analysis, we aimed to summarize earlier studies on the association of overweight and obesity with risk of dental caries in children. METHODS: Relevant studies published up to December 2023 were identified through searches in PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar, using suitable keywords. All observational studies, including cross-sectional or cohort or case-control studies, about the association of each obesity index with risk of dental caries in children which reported odds ratio (OR), hazard ratio (HR), or relative risk (RR) and 95% CIs, were included. Studies involving adults, randomized clinical trials, studies on animals or pregnant women, and studies on other dental disorders were excluded. Risk of bias was assessed using standard methods for observational studies. A total of 22 studies including 40673 participants were included. Studies were pooled using the random-effect model, and results were synthesized with subgroup analyses and assessments of heterogeneity. Limitations included potential publication bias and heterogeneity among study designs. The quality of the included studies was assessed using the Newcastle-Ottawa scale (NOS). RESULTS: Children at the highest category of BMI were 44% more likely to have early childhood caries (ECC) than those at the bottom (OR: 1.44; 95% CI: 1.16 to 1.78). Moreover, combined analysis also showed no significant association between waist circumference (WC) and risk of dental caries in children. However, significant linear and non-linear associations were found between BMI and risk of childhood dental caries. No publication bias was found for the relationship between BMI and the risk of ECC based on visual inspection of a funnel plot and Egger's test. CONCLUSIONS: This study showed a significant direct association between BMI and the risk of dental caries in children. Non-linear analysis showed higher risk of dental caries in children with higher BMI and also among underweight children. Further prospective studies are required to expand current knowledge in this issue. IMPACT STATEMENT: The findings of this study have significant implications for public health and dental care, suggesting association between BMI and the risk of dental caries in children. This comprehensive meta-analysis is among the first to summarize earlier publications on the association of obesity with risk of dental caries in children, highlighting the need for more accurate methods of obesity assessment and further research to understand this relationship better. These findings can help inform public health policies and interventions to reduce the prevalence of childhood obesity and dental caries.

Association of adipocytokine pathway gene polymorphisms with NAFLD in obese children. / è„‚è‚ªç»†èƒžå› å­é€šè·¯åŸºå› å¤šæ€æ€§ä¸Žè‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªæ€§è‚ç— çš„å ³è”.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has significant genetic susceptibility. Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis. However, the association between adipocytokine pathway genes and NAFLD remains unclear. This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. METHODS: A case-control study was conducted, dividing obese children into NAFLD and control groups. Peripheral venous blood (2 mL) was collected from each participant for DNA extraction. A total of 14 single nucleotide polymorphisms (SNP) in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing. Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children. Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. RESULTS: A total of 1 022 children were included, with 511 in the NAFLD group and 511 in the control group. After adjusting for age, gender, and BMI, multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models: heterozygote model (CG vs CC, OR=0.58, 95% CI 0.36 to 0.95, P=0.029), dominant model (GG+CG vs CC, OR=0.62, 95% CI 0.38 to 1.00, P=0.049), and overdominant model (CC+GG vs CG, OR=1.72, 95% CI 1.06 to 2.80, P=0.028). PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models: heterozygous model (CT vs CC, OR=1.51, 95% CI 1.10 to 2.07, P=0.011), dominant model (CT+TT vs CC, OR=1.50, 95% CI 1.10 to 2.03, P=0.010), overdominant model (CC+TT vs CT, OR=0.67, 95% CI 0.49 to 0.92, P=0.012), and additive model (CC vs CT vs TT, OR=1.40, 95% CI 1.07 to 1.83, P=0.015). No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD. GMDR analysis, adjusted for age, gender, and BMI, revealed no statistically significant interactions among the 14 SNPs (all P>0.05). CONCLUSIONS: Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children. However, no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.