title: Sex-Specific Mediating Role of Insulin Resistance and Inflammation in the Effect of Adiposity on Blood Pressure of Prepubertal Children.
abstract: OBJECTIVE
  To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR).
  
  
  METHODS
  We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP).
  
  
  RESULTS
  SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls.
  
  
  CONCLUSIONS
  The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation.
authors.affiliation: EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Liane
authors.initials: L
authors.lastname: Correia-Costa
authors.affiliation: EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Santos
authors.affiliation: EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.
authors.forename: Milton
authors.initials: M
authors.lastname: Severo
authors.affiliation: Division of Pediatric Nutrition, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Guerra
authors.affiliation: Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
authors.affiliation: EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Division of Pediatric Nephrology, Integrated Pediatric Hospital, Centro Hospitalar São João, Porto, Portugal.
authors.forename: Alberto
authors.initials: A
authors.lastname: Caldas Afonso
authors.affiliation: EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Barros
authors.affiliation: EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal; Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Azevedo
mesh_terms: D050154:Adiposity / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D001835:Body Weight / Q000502:physiology*; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009765:Obesity / Q000473:pathology*; D012737:Sex Factors