Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children.
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.
Mauras
Nelly
N
Nemours Children's Clinic, 807 Children's Way, Jacksonville, Florida 32207, USA. nmauras@nemours.org
Delgiorno
Charles
C
Kollman
Craig
C
Bird
Keisha
K
Morgan
Melissa
M
Sweeten
Shawn
S
Balagopal
Prabhakaran
P
Damaso
Ligeia
L
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
D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D002097:C-Reactive Protein