Understanding the Effects of Therapeutic Intervention on Cardiovascular Risk Markers, Insulin Resistance & Intra-Hepatic Fat Contents in Obese Children at Risk for Metabolic Syndrome

Nelly Mauras Principal Investigator

Funding: Thrasher Research Fund

Obesity, dyslipidemia, hypertension, and impaired glucose tolerance are increasingly recognized morbidities in children, predisposing youth to the hazards of early cardiovascular disease as adults. The term metabolic syndrome (syndrome X) has been coined to identify individuals where several of the named morbidities co-exist. We chose to narrowly focus this initiative on characterizing the role of inflammation and thrombosis in children and adolescents at risk for the metabolic syndrome and on the role of free fatty acid excess, as well as puberty in its development. Obese subjects (ages 8-18 years, n=80)) will be studied and their data compared with those of lean, age-and sex matched controls (n=80) using a battery of pro-inflammatory cytokines, hormones and growth factors in prepuberty and late puberty stages. A subgroup of pubertal subjects (n=30) identified with elevated inflammatory/thrombotic markers will be treated in a cross over design with life style changes only for 6 months or with the addition of medication for another 6 months (treatment order randomized). Metabolic tests are repeated at 3, 6 and 12 months. These studies will provide novel insights into the role of inflammation and thrombosis as co-morbidities in the metabolic syndrome in children and adolescents and further explore the interactions of pro-inflammatory markers with markers of insulin sensitivity and pubertal hormones.