ANCESTRAL ADMIXTURE AND INSULIN

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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. The prevalence of diabetes is higher among African-Americans (AA) and Mexican Americans (MA) vs European Americans (EA). These differences are not completely explained by demographic and/or health-related variables, suggesting that genetic factors are involved. With limited exceptions, the majority of observations regarding population differences in diabetes-related traits refer to EA and AA adults. However, several studies have demonstrated that racial differences in insulin-related phenotypes have their origin in childhood, making the prepubertal population an appropriate target for study. Hence, this study has been designed to investigate children of different racial groups. Studying prepubertal children is extremely important for a variety of reasons. First, by studying this sample we will be looking at the early pathophysiological factors, before many environmental and behavioral factors exert an influence in disease risk. In addition, understanding the etiology of diabetes-related traits in children will allow the development of intervention strategies at early stages of life that will increase disease prevention. The main objective of this study is to investigate the effect of genetic and environmental parameters on racial/ethnic differences in aspects of insulin secretion and action. The specific hypotheses to be tested are that, 1) Lower levels of European admixture (ADM) are associated with higher fasting insulin, lower insulin sensitivity (Si), and higher acute insulin response to glucose (AIRg); 2) In children with lower levels of European ADM, lower levels of physical activity will explain, in part, lower levels of Si and higher levels of fasting insulin and AIRg; in children with lower levels of European ADM, neither food intake nor socioeconomic status (SES) will have an effect on measures of fasting insulin, Si and AIRg; 3) Sequences of DNA across the genome represented by ancestry informative markers will be significantly associated with fasting insulin, Si, and AIRg. Testing will be conducted during two overnight GCRC visits, which will include collection of blood for genetic admixture analysis; a frequently sampled intravenous glucose tolerance test for determination of insulin sensitivity and secretion; and a meal tolerance test for examination of GI-derived insulinotropic hormones. Body composition, fat distribution, SES, dietary intake, and physical fitness also will be assessed.