Descripción del proyecto
Factores de riesgo cardiometabólico en pacientes obesos
El aumento de las tasas de obesidad de la población mundial constituye una amenaza para los sistemas de sanidad pública. Los principales costes sanitarios están relacionados con trastornos cardiometabólicos como la resistencia a la insulina, el colesterol alto y la hipertensión, los cuales a su vez aumentan el riesgo de diabetes tipo 2 y enfermedad cardiovascular. Curiosamente, algunas personas obesas son resistentes a las complicaciones cardiometabólicas, mientras que otras personas de peso normal padecen comorbilidades habitualmente asociadas a la obesidad. Estudios recientes del genoma han identificado múltiples loci genéticos asociados con un aumento de la deposición de grasa a nivel subcutáneo y global, apero con unos menores riesgos cardiometabólicos. El objetivo principal del proyecto financiado con fondos europeos GeneLifeCard es examinar si los factores genéticos y del estilo de vida eliminan el impacto del aumento de peso a largo plazo sobre el riesgo cardiometabólico. El estudio se llevará a cabo a través de metanálisis (análisis estadístico que combina los resultados de múltiples estudios) de cinco cohortes diferentes con múltiples mediciones del peso corporal y los rasgos cardiometabólicos.
Objetivo
The current obesity pandemic is a major threat to public health systems worldwide. The majority of obesity-related health care costs are due to cardiometabolic impairments such as insulin resistance, dyslipidemia, and hypertension, which increase the risk of type 2 diabetes and cardiovascular disease. However, many obese individuals seem resistant to cardiometabolic complications, the “metabolically healthy obese (MHO)”, while some normal weight individuals suffer from comorbidities similar to the obese. Genetic mechanisms may partly explain this paradox. Recent genome-wide studies have identified multiple genetic loci associated with increased overall body fat and subcutaneous fat deposition but lower cardiometabolic risk. Vice versa, the fat-decreasing alleles at these loci are associated with higher cardiometabolic risk. Some lifestyle factors, such as higher physical activity and smoking, are associated with lower body fat but show directionally opposite effects on cardiometabolic risk. At present, it remains unclear whether genetic predisposition to higher subcutaneous fat storage or healthy lifestyle behaviors may uncouple long-term weight gain from cardiometabolic risk during adulthood. Thus, the primary aim of the present project is to examine whether genetic and lifestyle factors abolish the impact of long-term weight gain on cardiometabolic risk by meta-analyses of five prospective cohorts with repeated measures of body weight and cardiometabolic traits. I will also examine whether these factors predict a MHO status in middle-age and the maintenance of such status over time. My results will provide new biological insights and may enable targeted lifestyle interventions against obesity-related cardiometabolic impairments. Moreover, the project will greatly advance my career by allowing me to learn highly valuable research skills in the area of genetic epidemiology, complementing my previous expertise in the field of cardiovascular epidemiology.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
1165 Kobenhavn
Dinamarca