ESTABLISHING THE PRECURSORS OF THE METABOLIC SYNDROME IN CHILDREN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Metabolic Syndrome (MSX) as defined in adults consists of abdominal obesity, dyslipidemia, hypertenions, insulin resistance, and a proinflammatory and prothrombotic state resulting in increased risk of cardiovascular disease. Obesity is an ever-increasing problem in children and is associated with development of type 2 diabetes, hypertension, pipid abnormalities and sleep apnea. Although these features appear similar to the MSX described in adults, the problem has not been well studied in the pediatric population. It is likely that the definition and pathogenesis of MSX may change with age. Description of the evolving pathogenesis in children could lead to development of age-specific definitions, and targeting age-specific pathology could greatly impact clinical care. It is hypothesized that the MSX in children is associated with early presentation of perpheral and hepatic insulin resistance, but normal insulin secretion, and that progressive worsening of insulin resistance leads to defects of insulin secretion secondary to glucose toxicity. It is further hypothesized that fatty acid metabolism is abnormal leading to lipotoxic damage and further insulin resistance. Investigators propose cross-sectional metabolic studies to characterize the metabolic changes associated with MSX in defined age groups (infants, toddlers, prepubertal children and adolescents).