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. There is a fundamental gap in understanding why the prevalence of type 2 diabetes is 2-3 times higher in American-Indians than in Caucasians. The objective of this application is to obtain data pertinent to insulin sensitivity, fat mass, and cardiovascular fitness among American-Indian children. The pattern of change in these variables over two-years will be examined in a group of obese American-Indian and Caucasian children with at least one first-degree relative with confirmed type 2 diabetes. The three specific aims are: 1) Compare the rate of change in insulin sensitivity over a two-year period in a cohort of obese American Indian children and a similar cohort of Caucasian children. 2) Compare the rate of change in the mass and distribution of fat over a two-year period in a cohort of obese American-Indian children and a similar cohort of Caucasian children. 3) Compare the rate of change in cardiovascular fitness over a two-year period in a cohort of obese American-Indian children and a similar cohort of Caucasian children. The approach is innovative because the concept that temporal differences in metabolic and physiologic mechanisms contributing to the greater incidence of type 2 diabetes in American-Indians has yet to be fully understood. The proposed research is significant because the results of this study are expected to lead to mechanistically based research that focuses on the most likely temporal candidates. The sharper focus is expected to accelerate the pace at which causal relationships are established and, therefore, the speed with which new interventions and strategies can be developed and implemented to reduce the risk of type 2 diabetes to the American-Indian community.
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