ESPE Abstracts

Background: Severe early-onset obesity (SEOO) in children is more frequently observed in subjects with genetic disorders of which those of leptin pathway can be analyzed biochemically and genetically.

Objectives: The aim of the study was to investigate anthropometrics and leptin parameters, specifically searching for bio-inactive leptin, in children with SEOO.

Methods: Study cohort includes children who developed a BMI>25kg/m² before an age of 6years and who were presented at individual study centers (Germany: n=1, Poland: n=4 |German-Polish consortium, EOL-GPS) between July 2015 and Dec 2017. Anthropometric parameters (weight[kg], height[cm], BMI[kg/m²]) were measured and a serum blood sample was taken. If possible, parental anthropometric parameters (weight[kg], height[cm], BMI[kg/m²]) and blood samples were ascertained. Levels of total leptin [totLep,ng/ml¹], bio-inactive leptin [bioLep^1,2] and soluble leptin receptor [sLEPR¹] were measured in serum samples. Quotient of bioLEP/totLep and LEP-SDS³ were calculated.

Results: Data of n=50 children (female: 56%, Tanner stage 1: 85.7%, age at blood sampling: 7.7±4.5years, BMI: 32.2±9.3kg/m²; BMI-SDS: 3.7±0.9; %BMIP95: 157.3±30.7%), of n=45 mothers and n=43 fathers (n=42 trios) were included in statistical analysis. Based on measured leptin parameter, we identified no child with leptin deficiency or bio-inactive leptin. Measured totLEP concentrations in children ranged between 25.2 and 49.2ng/ml (interquartile range). Within correlation analyses between leptin parameters and anthropometrics in children, we observed that: totLep concentrations were positively correlated with BMI values (r=0.86, P<0.05) and negatively correlated with sLEPR (r=−0.39, P<0.05); sLEPR levels were negatively correlated with age (r=−0.53, P<0.05) and BMI values (r=−0.44, P<0.05); LEP-SDS values were negatively correlated with BMI values (r=−0.70, P<0.05). Analysis of trios identified that 80% of parents were overweight/obese.

Conclusions: Disorders of leptin as a cause of obesity are rare. Also in this cohort with SEOO we identified no new cases of children with leptin deficiency or bio-inactive leptin. We confirmed previously published observations of negative associations between sLEPR, age and BMI values in children. The strong negative correlation between LEP-SDS and BMI values could be interpreted as relative leptin deficiency. However further collection and analysis of severely early-onset obese children must prove whether the relationship between BMI and leptin parameters is definitely different from normally weighing children.

Reference:

¹Mediagnost, Reutlingen, Germany: www.mediagnost.de.

²Wabitsch et al. Eur J Endocrinol. 2017;176(3):315–322.

³Blum et al. JCEM. 1997;82(9):2904–10.