This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The incidence of type 2 diabetes among African-Americans is greater than among Caucasian-Americans. Data from the principal investigator and other groups has suggested that insulin sensitivity is lower, and glucose-stimulated insulin concentration is higher, among African-Americans vs Caucasian Americans. These differences may contribute to observed ethnic differences in disease occurrence. However, the nature of potential ethnic differences in insulin sensitivity, secretion, and clearance has not been thoroughly determined. The proposed project will: 1) characterize insulin sensitivity, secretion, and clearance in African-Americans and Caucasian-Americans, and 2) determine whether depressed insulin sensitivity (greater insulin resistance) or hyperinsulinemia is likely to be the primary physiological difference conferring greater disease risk to African-Americans. All subjects will be female because type 2 diabetes disproportionately affects adolescent African-American girls and adult African-American women. Six groups will be formed based on ethnicity (Caucasian-American, African-American), age (prepubertal, young adult, postmenopausal), and obesity status (non-obese, obese). A total of 180 subjects will be tested as inpatients in the GCRC. Testing will consist of a frequently-sampled, intravenous, glucose tolerance test (FSIGT) incorporating stable-isotopically-labeled glucose, C-peptide determination, and minimal modeling. Body composition and fat distribution will be determined by dual-energy X-ray absorptiometry and computed tomography, respectively.The specific hypothesis to be tested is: Lower insulin sensitivity in African-Americans vs Caucasian-Americans is due to lower hepatic insulin extraction (clearance); the resultant chronic hyperinsulinemia ultimately results in peripheral (skeletal muscle) insulin resistance. The GCRC will provide dietary control prior to testing (Bionutrition); perform the FSIGT (Nursing); process the blood samples (Processing Laboratory); and analyze samples for hormones and substrates (Physiology and Metabolism Core Laboratory).
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