This revised grant application is a competing continuation of the project R01HD38356 Sexual Maturity in US Children which is a cross-sectional study of sexual maturation and body weight, height, and BMI. The competing renewal proposes to analyze long-term serial data collected from birth to 20 years of age in 287 boys and 269 girls in the Fels Longitudinal Study. In girls breast development (thelarche) usually precedes the appearance of pubic hair (adrenarche), and in boys genital development (gonadarche) usually precedes adrenarche. In each sex there is an alternate pathway in which adrenarche precedes thelarche in girls or gonadarche in boys.
The specific aims are to examine, longitudinally, (i) the impact of birth weight and body composition on the two pubertal pathways and (ii) the effects of rate of maturation in boys and girls on contemporaneous and subsequent body fat, fat distribution, lean body mass, blood pressure, bone mass, lipid profiles, and insulin resistance. These parameters are important in view of their relationship to cardiovascular disease, type 2 diabetes, and osteoporosis later in life. This application rests on the idea that body composition is related to the events of puberty and adolescent growth by closely intertwined interactions between the gonadotropic axis, the somatotropic axis, adrenal androgens, leptin, and insulin. Longitudinal modeling of these factors in the Fels data set will yield mechanistic insights into the pubertal process and will also aid in predicting those children who are most at risk for components of the metabolic syndrome later in life. In the Fels Longitudinal Study we have collected long-term serial data for indicators of maturation and body composition, and leptin, insulin, IGF-1, DHEAS, and gonadal steroids as well as risk factors for cardiovascular disease, type 2 diabetes, and osteoporosis. These data provide a unique opportunity to study the relationships between body composition and sexual maturation in boys and girls. The Fels participants are enrolled into the study at birth and are not selected in regard to factors associated with any particular body composition or clinical condition. The relationships revealed and the inferences drawn from the proposed study should reflect the impact of birth weight and body composition on the natural history of sexual maturation and the development of fat and fat distribution, lean body mass, bone mineral content and related risk factors for disease later in life.
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