Obesity without Established Comorbidities of the Metabolic Syndrome Is Associated with a Proinflammatory and Prothrombotic State, Even before the Onset of Puberty in Children

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 3; pp. 1060 - 1068
• Main Authors: Mauras, Nelly, DelGiorno, Charles, Kollman, Craig, Bird, Keisha, Morgan, Melissa, Sweeten, Shawn, Balagopal, Prabhakaran, Damaso, Ligeia
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.03.2010; Copyright by The Endocrine Society
• Subjects: Absorptiometry, Photon; Adolescent; Analysis of Variance; Biological and medical sciences; Body Composition - physiology; Body Mass Index; C-Reactive Protein - metabolism; Carbohydrate Metabolism - physiology; Child; Dyslipidemias - complications; Dyslipidemias - metabolism; Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Feeding. Feeding behavior; Female; Fibrinogen - metabolism; Fundamental and applied biological sciences. Psychology; Glucose Intolerance - complications; Glucose Intolerance - metabolism; Humans; Hypertension - complications; Hypertension - metabolism; Inflammation - complications; Inflammation - metabolism; Interleukin-6 - blood; Male; Medical sciences; Metabolic Syndrome - complications; Metabolic Syndrome - metabolism; Obesity - complications; Obesity - metabolism; Plasminogen Activator Inhibitor 1 - blood; Puberty - metabolism; Risk Factors; Sex Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Waist Circumference - physiology; Endocrinopathy; Human; Obesity; Puberty; Nutrition; Nutrition disorder; Cardiovascular disease; Metabolic diseases; Inflammation; Metabolic syndrome; prothrombotic state; Concomitant disease; Age of onset; Polypathology; Child; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-1887

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. Subjects and 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). Conclusion: 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. Childhood obesity is associated with a proinflammatory, prothrombotic state before other comorbidities of the metabolic syndrome are present, and even before the onset of puberty.