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. Hypothesis Adolescents with diabetes do not acquire appropriate peak bone mass because of inadequate calcium intake and poor metabolic control which leads to derangement of the IGF system Based on our hypothesis, we have formulated the following Specific Aims: ? Specific Aim 1 To evaluate the role of calcium intake and metabolic control in the acquisition of peak bone mass in adolescents with type 1 and type 2 diabetes In Specific Aim 1, we determine calcium intake and peak bone mass density (BMD) in adolescent patients with: type 1 diabetes, type 2 diabetes and obese patients. Because the most rapid bone mass acquisition is in the mid-adolescence we plan to recruit patients between 13 and 18 years of age. We select patients who had diabetes for at least 3-year. We will stratify them based on their chronic metabolic control defined as a two-year stable HbA1c. Outcome measures are: dual x-ray absoptiometry (DEXA), calcium intake, biomarkers of bone metabolism and, physical activity. We will determine if patients' calcium intake and metabolic control correlate with the acquisition of peak bone mass attained per DEXA. We will define differences in bone density and calcium intake in patients with type 1 versus type 2 and how obesity and exercise can contribute to these differences. We expect that adolescents with diabetes fail to attain the appropriate acquisition of BMD as a result of the underlying chronic disease and poor calcium intake. ? Specific Aim 2 To determine if a derangement of the IGF system in adolescents with diabetes determines a failure to attain peak bone mass In Specific Aim 2, we will determine the circulating components of the IGF system in adolescents with type 1 and type 2 diabetes and in obese patients. Outcome measures are: IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6. We will determine how the derangement of the IGF system in patients with poorly controlled diabetes correlates with the acquisition of peak bone mass density. We expect that in patients with diabetes low circulating levels of free bioavailable IGF-I levels will correlate with metabolic control and failure to attain the appropriate BMD.
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