This grant application is a longitudinal cohort study submitted in response to the NIH Request for Applications, RFA-HD-03-033, """"""""Establishing the Precursors of the Metabolic Syndrome in Children """""""". Our overall goal is to link the metabolic syndrome in adults [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) to their childhood risk factors using long-term serial data collected from birth in 350 adult males and 348 adult females in the Fels Longitudinal Study. The ATP llI defines the metabolic syndrome in adults as having a cluster of three, four, or five risk factors that exceed criterion values, namely, waist circumference >102 cm for men and >88 cm for women;blood pressure >130/>85 mm Hg;plasma triglyceride level >150 mg/dL;plasma HDL-cholesterol level <40 mg/dL for men and <50mg/dL for women;and fasting plasma glucose >110 mg/dL. We propose (1) to determine if the onset of pathological values for any of the components of the metabolic syndrome begins in childhood;and, if so, to establish childhood criterion values for these biomarkers;(2) to examine in these 698 Fels adults changes and sexual dimorphism in values collected during their pubertal years for body fat, fat distribution, fat-free mass, lipid profiles, insulin resistance, blood pressure, leptin, adiponectin and C-reactive protein (CRP) in relation to the presence or absence of the metabolic syndrome in adulthood;and, (3) to relate adulthood changes in cardiac structure and hemodynamic parameters to contemporaneous changes in body fat, fat distribution, and fat-free mass and to metabolic syndrome over a three-year interval. We will conduct the proposed study using both the NCEP ATP III criterion of 110 mg/dL and the American Diabetes Association's (ADA) newly recommended criterion of 100 mg/dL for impaired fasting plasma glucose in order to elucidate the diagnostic implications of the lower threshold. Elucidating adverse relationships by linking childhood data to adult pathology may lead to the ability to detect children at elevated risk for the metabolic syndrome and, by implication, for type 2 diabetes mellitus and cardiovascular disease. The Fels long-term serial records provide a unique opportunity to accomplish our aims in an economical and efficient manner. Participants in the Fels Longitudinal Study are enrolled at birth and are not selected in regard to factors associated with any clinical condition. Consequently, the relationships revealed and the inferences drawn from the proposed study should reflect the natural history of the development of obesity, hypertension, dyslipidemia, and impaired glucose tolerance, and thus, should lead to the early identification of children at risk for the metabolic syndrome.
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