The fundamental purpose of these studies is to determine the utility of serum IGF-I and IGF binding protein concentrations in predicting improvement in growth rates or entry into an anabolic state in response to nutritional support. Four studies are to be undertaken in the proposal. Children who are growing at normal states will be fed either energy or protein restricted diets and the response of total serum IGF-I and II concentrations as well as each of the three IGF binding proteins will be measured. They will then be fed a control diet and the responses of each of the parameters will be correlated with changes in nitrogen balance to determine if they predict improvement. Three studies will be conducted in children who are growing suboptimally to determine if short term changes in these serum proteins predict improvement in the long term growth response in response to improved dietary intake. Children with syndromes associated with impaired nutrient absorption will be studied while receiving hyperalimentation therapy. The goal will be to determine if changes in the plasma binding proteins and IGF-I correlate with changes in weight gain and growth rates during nutritional supplementation and whether they can predict the rate of improvement in these indices. A third study will utilize hypopituitary subjects that are receiving growth hormone but who are growing at either accelerated or sub-optimal rates. Subjects will be divided into two groups based on their growth rate and studied for one year. During this interval the subjects will be hospitalized 3 times and fed an optimal diet. Improvement in nitrogen balance, serum IGF-I, IGFBPs and weight gain will be assessed during these periods. It is anticipated that those subjects who are not growing at a maximal rate will be ingesting suboptimal diet and will show improvement on the optimal diet. A final study will assess growth and changes in IGF-I and IGF binding proteins in premature newborns. We will correlate growth rates with changes in plasma IGF-I and IGF binding proteins and determine whether this profile of tests predicts those subjects who are growing at a rapid rate versus those who are having continuing feeding problems and continuing to grow at a slow rate. The results of these studies should enable us to determine whether measurements of IGF-I and IGF binding proteins predict is a child's diet is optimal for a normal growth rate and whether these tests will have potential clinical utility outside of a research setting.
