Study of the metabolic health of obese children and adolescents by clinical and metabolomics research

Childhood obesity is a multifactorial complex disorder which is closely associated with the presence of metabolic complications such as insulin resistance, the metabolic syndrome, prediabetes and premature coronary disease. In the past decades, the prevalence of extreme childhood obesity has rapidly increased. To define morbid childhood obesity and to calculate its prevalence, the international (IOTF) BMI cut-off points which correspond to a BMI higher than 40 at the age of 18 years were established. The future application of these BMI cut-off values in clinical research and daily practice will eventually lead to a simple and costeffective screening of morbid childhood obesity. Additional research showed that morbidly obese children have higher fasting insulin and systolic blood pressure levels compared to less extremely obese children. Apart from the use of the BMI to screen for metabolic complications in obese children, other screening methods were also studied, including the OGTT curve and metabolically “healthy” obesity (MHO). This study revealed that end-pubertal obese girls with a monophasic OGTT shape pattern showed early signs of β-cell insulin secretory failure as opposed to those with a biphasic or triphasic shape pattern. In addition, MHO children and adolescents had significantly lower levels of fasting insulin, triglycerides and TG/HDL-C ratio as compared to MUO children. In addition to clinical research, NMR-based metabolomics was applied to identify biomarkers of metabolic complications of childhood obesity. Hereto, 1H-NMR experimental analysis was first optimized and a robust and practical protocol for sample collection and processing in a clinical setting was developed. Using 1H-NMR-based plasma metabolomics, the metabolic profile of obese and normal-weight children and adolescents was determined and compared. As an extension, the plasma metabolic profile of a metabolically “healthy” but obese (MHO) phenotype was investigated. This showed that the obese and metabolically unhealthy phenotype was characterized by an increased lipid content, decreased levels of cholinecontaining phospholipids, an increased glycolytic activity, low-grade inflammation, and alterations in energy metabolism. In addition to this, it appeared that triglyceride concentrations were strongly correlated to the obese metabolic unhealthy phenotype. In brief, the fundamental clinical and metabolomics research performed in this doctoral project provides a basis for the future development of clinically useful screening tools for the early detection of obesity and associated metabolic complications in children and adolescents.

Publication year:2015

Accessibility:Open