This is an application in response to a program announcement for studies to examine racial/ethnic differences in the etiology of type 2 diabetes. The PI proposed a cross-sectional design to examine the time course of change in insulin and insulin resistance that lead to diabetes. The proposed project will: 1) characterize insulin sensitivity, secretion and clearance in African-Americans (AA) and Caucasian-Americans, and 2) determine whether depressed insulin sensitivity (greater insulin resistance) or hyperinsulinemia is likely to be the primary defect. All information regarding differences in insulin sensitivity, secretion and clearance will be obtained from a single frequently sampled intravenous tolerance test and subsequent minimal modeling. A stable isotope of glucose will be used to differentiate glucose uptake from glucose production. Measurement of C-peptide will be performed to differentiate insulin secretion from insulin clearance. Both obese and non-obese AA and C individuals will be studied to examine obesity-ethnic interactions. Free fatty acid concentrations will be measured throughout the glucose tolerance test to begin to address the potential physiological ramifications of chronic hyperinsulinemia among AA subject. The PI believes that the primary defect in conferring lower insulin sensitivity in AA vs C subjects is a defect in hepatic insulin extraction (clearance). The chronic hyperinsulinemia that results from this defect will ultimately result in peripheral (skeletal muscle) insulin resistance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK058278-04
Application #
6655709
Study Section
Nutrition Study Section (NTN)
Program Officer
Linder, Barbara
Project Start
2000-09-30
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$207,942
Indirect Cost
Name
University of Alabama Birmingham
Department
Nutrition
Type
Schools of Allied Health Profes
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Piccinini, Francesca; Polidori, David C; Gower, Barbara A et al. (2017) Hepatic but Not Extrahepatic Insulin Clearance Is Lower in African American Than in European American Women. Diabetes 66:2564-2570
Fisher, Gordon; Alvarez, Jessica A; Ellis, Amy C et al. (2012) Race differences in the association of oxidative stress with insulin sensitivity in African- and European-American women. Obesity (Silver Spring) 20:972-7
Ellis, Amy C; Alvarez, Jessica A; Granger, Wesley M et al. (2012) Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women. Metabolism 61:634-40
Chandler-Laney, Paula C; Phadke, Radhika P; Granger, Wesley M et al. (2011) Age-related changes in insulin sensitivity and *-cell function among European-American and African-American women. Obesity (Silver Spring) 19:528-35
Chandler-Laney, Paula C; Phadke, Radhika P; Granger, Wesley M et al. (2010) Adiposity and *-cell function: relationships differ with ethnicity and age. Obesity (Silver Spring) 18:2086-92
Alvarez, Jessica A; Ashraf, Ambika P; Hunter, Gary R et al. (2010) Serum 25-hydroxyvitamin D and parathyroid hormone are independent determinants of whole-body insulin sensitivity in women and may contribute to lower insulin sensitivity in African Americans. Am J Clin Nutr 92:1344-9
Goree, Laura Lee T; Darnell, Betty E; Oster, Robert A et al. (2010) Associations of free fatty acids with insulin secretion and action among African-American and European-American girls and women. Obesity (Silver Spring) 18:247-53
Casazza, Krista; Phadke, Radhika P; Fernandez, Jose R et al. (2009) Obesity attenuates the contribution of African admixture to the insulin secretory profile in peripubertal children: a longitudinal analysis. Obesity (Silver Spring) 17:1318-25
Munoz, Julian; Lok, Kerry H; Gower, Barbara A et al. (2006) Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with reduced insulin secretion in nondiabetic women. Diabetes 55:3630-4
Hunter, Gary R; Byrne, Nuala M; Gower, Barbara A et al. (2006) Increased resting energy expenditure after 40 minutes of aerobic but not resistance exercise. Obesity (Silver Spring) 14:2018-25

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