title: Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children.
abstract: BACKGROUND
  Metabolic syndrome (MS)-related comorbidities in obesity, such as hypertension, dyslipidemia, and glucose intolerance, are increasingly recognized in children, predisposing them to early cardiovascular disease.
  
  
  OBJECTIVE
  The objective of the study was to investigate whether markers of inflammation and prothrombosis are abnormal in obese children without established MS comorbidities across puberty, as compared with lean, age-matched controls.
  
  
  METHODS
  Obese children (body mass index >95%) with normal fasting glucose, blood pressure, cholesterol and triglycerides were recruited; lean controls (body mass index 10-75%) had no first-degree relatives with MS. High-sensitivity C-reactive protein (hsCRP), IL-6, plasminogen activator inhibitor 1, and fibrinogen concentrations were measured. Body composition was assessed by waist circumference and dual-energy x-ray absorptiometry.
  
  
  RESULTS
  Of 623 children screened, 203 enrolled (106 males, 97 females), aged 7-18 yr, 115 obese, 88 lean (balanced for age and gender), 99 prepubertal, and 104 pubertal. Many screen failures were due to silent comorbidities. Obese subjects with insulin resistance but without MS comorbidities had about 10 times higher hsCRP concentrations than controls and higher fibrinogen, IL-6, and plasminogen activator inhibitor-1 (P < 0.01 all). Differences were significant, even in the prepubertal cohort. hsCRP and fibrinogen correlated with waist circumference (r = 0.73 and 0.40, respectively) and percent fat mass (r = 0.76 and 0.47) (P < 0.0001).
  
  
  CONCLUSIONS
  Childhood obesity per se is associated with a proinflammatory and prothrombotic state before other comorbidities of the MS are present and even before the onset of puberty. Whether biomarkers like hsCRP and fibrinogen are useful in assessing cardiovascular risk and whether these abnormalities are reversible with earlier therapeutic interventions in very young obese children requires further study.
authors.affiliation: Nemours Children's Clinic, 807 Children's Way, Jacksonville, Florida 32207, USA. nmauras@nemours.org
authors.forename: Nelly
authors.initials: N
authors.lastname: Mauras
authors.forename: Charles
authors.initials: C
authors.lastname: Delgiorno
authors.forename: Craig
authors.initials: C
authors.lastname: Kollman
authors.forename: Keisha
authors.initials: K
authors.lastname: Bird
authors.forename: Melissa
authors.initials: M
authors.lastname: Morgan
authors.forename: Shawn
authors.initials: S
authors.lastname: Sweeten
authors.forename: Prabhakaran
authors.initials: P
authors.lastname: Balagopal
authors.forename: Ligeia
authors.initials: L
authors.lastname: Damaso
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000704:Analysis of Variance; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000502:physiology; D002648:Child; D050171:Dyslipidemias / Q000150:complications* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D018149:Glucose Intolerance / Q000150:complications* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011627:Puberty / Q000378:metabolism*; D012307:Risk Factors; D012737:Sex Factors; D055105:Waist Circumference / Q000502:physiology
chemical_list: D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D002097:C-Reactive Protein