Metabolically Healthy Obesity in Pediatric Population- Prevalence, Predictors and the Effect of Heart Rate Variability

Scientific background:

The global epidemic of childhood obesity, with the accompanying rise in the prevalence of endocrine, metabolic, and cardiovascular comorbidities in youth, represents one of the most important public health issues of the modern world (1-4). The earlier occurrence and increase in the prevalence of both pediatric obesity and metabolic syndrome (MS) leads to a potential decline in life expectancy, meaning that the youth of today could be the first generation to live shorter lives than their parents (2, 4-6).

In the context of the childhood obesity pandemic, a distinct subgroup of youth with obesity less prone to the development of metabolic disturbances, called "metabolically healthy obese" (MHO), has come into focus (7, 8). Despite having obesity, MHO individuals display a "favorable" metabolic profile, with preserved insulin sensitivity, normal blood pressure and glucose regulation, normal lipids and liver enzymes, as well as a normal hormonal, inflammation, and immune profile (9-13). Although MHO status might not necessarily translate into lower mortality, and can crossover to "metabolically unhealthy obese" (MUO) phenotype during puberty, defining the MHO subpopulation within the youth with obesity is of high importance in order to elucidate the mechanisms protecting against the clustering of cardiometabolic risk factors, and for its clinical, preventive, and therapeutic decision-making implications (4, 7, 13-15).

Few studies evaluated predictors and risk factors for MUO (14-15). However, these were based on variety of definitions and criteria used for defining MHO. moreover, little is known about the mechanisms of development of metabolic disturbance in pediatric obesity. More data is needed in order to identify the parameters which have the highest ability to predict clinically significant outcomes. Cardiac autonomic function, which can be measured non-invasively with heart rate variability, has been suggested as a potential mechanism underlying the development of metabolic syndrome and cardiovascular disease (16). Autonomic dysfunction characterized by reduced heart rate variability was found to predict coronary heart disease, type 2 diabetes mellitus and of all-cause and cardiac mortality (17-20) in adult population. However, the effect of reduced heart rate variability on metabolic syndrome in pediatric population and the influence of nutritional intervention with weight reduction on heart rate variability is not known. We aimed to investigate clinical, anthropometric, and socio-demographic and lifestyle predictors of MHO in this group, to describe HRV in children with obesity, and to find correlation to the metabolic syndrome or metabolic syndrome progression or improvement, in order to reveal if HRV can serve as a predictor to metabolic disturbance in pediatric obesity population.

Study design: