1322-P: Early Environment and Genetic Predisposition to Metabolically Obese Normal-Weight Phenotype in Children: Findings from a Cohort Study

Abstract

Some normal-weight individuals are predisposed to obesity-related cardiometabolic abnormalities, namely, metabolically obese normal weight (MONW). Studies of the MONW phenotype in youths are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1,484 normal-weight Chinese children aged 6-18, including 588 subjects with MONW phenotype, were recruited from the Beijing Children and Adolescents Metabolic Syndrome cohort. Birth weight (BW) childhood lifestyle and socio-economic factors, and 20 genetic variants which had been previously shown to be associated with BMI or T2D in East Asian adults were examined for the associations with pediatric MONW phenotype. Metabolically unhealthy was defined as having any metabolic syndrome component or HOMA-IR≥3.0. Independent risk factors for MONW phenotype were low BW, increased BMI, and lower levels of physical activity, maternal education and family income (all P<0.05), while amongst genetic variants, CDKAL1 rs2206734 shown the strongest association with MONW (OR per C allele=0.81, 95% CI=0.70-0.95; P=0.008). Moreover, rs2206734 interacted with BW on MONW phenotype (P interaction=0.005). Every C allele was associated with a 50% reduced risk of MONW in high (>75th percentile) BW (95% CI=0.34-0.72; P=0.0002), while the genetic associations were nonsignificant in intermediate and low (≤75th percentile) BW (P>0.1). The effect of high BW on the CDKAL1-MONW relationship could be further augmented by the combined impact of beneficial childhood environmental factors (physically active, high maternal education and family income) (Pinteraction=0.017). In conclusion, both early environments, particularly BW, and genetic predisposition plus their interaction were associated with MONW in children. Our study provides new insights into MONW and suggests a long-term prevention strategy, especially in genetically susceptible individuals. Disclosure M. Li: None. G. Li: None. S. Gao: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Roche Diagnostic USA. Research Support; Self; Jaeb Center for Health Research, National Institute of Allergy and Infectious Diseases, Sanofi-Aventis. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Funding National Key Research Program of China (2016YFC1304801); Beijing Municipal Science & Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science & Technology Star Program (2004A027), Novo Nordisk (2011A002); National Key Program of Clinical Science (WBYZ 2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001)