MetHyOS: A longitudinal approach to metabolically healthy obesity: from inflammation to cardiovascular risk profile (PTDC/DTP-EPI/6506/2014)
Portuguese national funding agency for science research and technology
Instituto de Saúde Pública da Universidade do Porto (ISPUP/UP) • Epidemiology Research Unit - Institute of Public Health, University of Porto (EPIUnit)
The impact of obesity on the development of cardiovascular disease (CVD) and its association with increased all-cause mortality it is widely recognized. However, some obese individuals show an absence of metabolic disorders, with a risk for CVD and total mortality comparable to of the observed in normal weight individuals. This phenomenon has been recognized among researchers as metabolically healthy obesity (MHO), despite no standardized criteria has been yet established to define it. Moreover, data concerning the long term benefits of this phenotype are still scarce and conflicting. There is increasing evidence that one of the underlying mechanisms contributing to these different phenotypes might be low-grade inflammation, but the usefulness of inflammatory markers to predict cardiovascular risk is still unclear for paediatric age. Understanding what prevents these obese individuals from developing adverse metabolic changes is vital to identify those that would benefit the most from interventions and to improve criteria for risk-stratification of future CVD.
This project aims to examine obesity-induced inflammation and to identify inflammatory markers for prediction of future cardio metabolic risk, focusing on the occurrence of metabolically healthy obesity and unhealthy normal weight. We will also investigate how the distribution of body fat (visceral adipose tissue/peripheral fat) and its tracking from adolescence to adulthood determines inflammatory responses and future cardio metabolic risk.
The specific objectives are:
1) To understand how adiposity (trajectory and distribution) throughout paediatric age relates to different adiposity phenotypes (MHO and MUNW), and impact on cardiometabolic risk;
2) To assess the relationship between adiposity and metabolic risk profile, testing the direct effects and those mediated by inflammatory processes;
3) To identify inflammatory markers in paediatric age that could predict increased cardiovascular risk later in life, beyond general adiposity measures such as BMI.
The project will be developed as part of EPITeen (Epidemiological Investigation of Teenagers Health in Porto), a cohort of urban adolescents born in 1990 and enrolled at Porto private and public schools. The assembling was performed in 2003, when the participants were 13 years old, and they were re-evaluated in 2007/2008 school year and in 2011-2013. The fourth evaluation is currently on-going, at 24 years of age. At baseline we identified 2787 eligible adolescents and we obtained a 77.5% overall proportion of participation, similar in public and private schools (77.9% vs. 77.0%, p=0.709). The final sample included 2159 13- year-old adolescents. The proportion of re-evaluation was 79.4% in the second study-wave and 60% in the third. Each evaluation comprised self-administered questionnaires and a physical examination. For this project, aside from using the available data from previous evaluations, we will collect information regarding new events on individual clinical history data and reproductive history data, as well as changes regarding dietary habits and physical activity, using a short self-reported questionnaire. Such as in past evaluations, a physical examination will be performed by a team of experienced health professionals, following the same procedures, and will include anthropometrics (weight and height, body circumferences and skinfold thickness) and bioelectric impedance. Additionally, in order to obtain a more valid and feasible assessment of body fat distribution, a dual-energy x-ray absorptiometry measurement will be performed. Inflammatory markers, such as high sensitivity C-reactive protein, tumour necrosis factor-α and interleukin-6, will be assessed by obtaining a 12-hour overnight fasting period intravenous blood sample, taken from
an antecubital vein. Assessed cardiovascular risk factors will include blood pressure and analytical parameters as blood glucose, hemoglobin A1c, insulin, total cholesterol, high-density lipoprotein cholesterol and triglycerides, derived from serum samples. The use of a longitudinal approach in a population-based cohort will allow us to add a better understanding of the MHO phenotype, providing important insights on the association between obesity and cardiovascular disease, and on the role of low-grade inflammation as mediator of this association. It will also improve current knowledge of these effects in a real context, essential to design preventive measures suitable for the population and to estimate the impact of population-based interventions.