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Identification of Genetic and Environmental Factors Predicting Metabolically Healthy Obesity in Children: Data From
Lujiao Li1, Jinhua Yin1, Hong Cheng1
1Department of Endocrinology (L.L., J.Y., Y.W., Ming.L.), Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China; Department of Epidemiology (H.C., J.M.), Capital Institute of Paediatrics, Beijing 10020, People's Republic of China; Department of Endocrinology (S.G.), Chaoyang Hospital, Capital Medical University, Beijing 100043, China; and Department of Biostatistics and Epidemiology (Mingy.L.), Division of Endocrinology (S.F.A.G., Ming.L.), The Children's Hospital of Philadelphia, Perelman School of Medicine, Division of Human Genetics, (S.F.A.G.), The Children's Hospital of Philadelphia Research Institute, Department of Pediatrics (S.F.A.G.), Perelman School of Medicine, University of Pennsylvania; Philadelphia, Pennsylvania 19104.
Insights
Approximately one-third of obese Chinese children are metabolically healthy obese (MHO). Both genetic and environmental factors, along with their interactions, predict MHO status in pediatric populations.
Area of Science:
- Pediatric Endocrinology
- Obesity Research
- Metabolic Health
Background:
- Limited data exist on metabolically healthy obesity (MHO) in children.
- Understanding MHO in pediatric populations is crucial for early intervention.
Purpose of the Study:
- To determine the prevalence of MHO in Chinese children.
- To investigate environmental and genetic factors influencing MHO status.
Main Methods:
- Cross-sectional study of 1213 obese children (aged 6-18 years).
- MHO classification based on insulin resistance or cardiometabolic risk factors.
- Assessment of 22 genetic variants, lifestyle, socioeconomic status, and birth weight.
Main Results:
- Prevalence of MHO with insulin resistance (MHO-IR) was 27.1%; MHO with cardiometabolic risk (MHO-CR) was 37.2%.
- Waist circumference, walking to school, and KCNQ1-rs2237897 were significant predictors.
- Acanthosis nigricans, birth weight, soft drink consumption, maternal education, and KCNQ1-rs2237892 also predicted MHO-IR, with significant interactions observed.
Conclusions:
- About one-third of obese Chinese children exhibit MHO.
- Genetic predisposition and environmental factors interact to influence MHO status.
- Findings offer insights into obesity heterogeneity and potential optimization of pediatric obesity interventions.
Context:
Available data related to the metabolically healthy obesity (MHO) phenotype are mainly derived from studies in adults because studies during childhood are very limited to date.
Objective:
The objective of the study was to determine the prevalence of MHO in Chinese children and to investigate environmental and genetic factors impacting on MHO status.
Design:
This was a cross-sectional study.
Participants:
A total of 1213 children with a body mass index at the 95th percentile or greater aged 6–18 years were included in this study. Participants were classified as MHO or of metabolically unhealthy obesity based on insulin resistance (IR) or cardiometabolic risk (CR) factors (blood pressure, lipids, and glucose). Twenty-two genetic variants previously reported from genome-wide association studies of obesity and diabetes plus the environmental factors of lifestyle, socioeconomic status, and birth weight was assessed.
Results:
The prevalence of MHO-IR and MHO-CR were 27.1% and 37.2%, respectively. Waist circumference 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 drink consumption, the 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 (odds ratio 1.31 [95% confidence interval 1.05–1.63]) and between rs2237892 and consumption of soft drinks on MHO-IR (odds ratio 0.80 [95% confidence interval 0.68–0.94]).
Conclusions:
Approximately 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. This study provides novel insights into the heterogeneity of obesity and has the potential to impact the optimization of the intervention options and regimens in the management of pediatric obesity.
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