Obesity, diabetes and heart disease are characterized by resistance to insulin as a glucoregulatory hormone. African Americans, particularly African American women suffer disproportionately from these three conditions. We believe that sex differences in sensitivity to insulin?s ability to suppress lipolysis contribute to the accelerated development of obesity, diabetes and heart disease in African American women. The hypothesis of this research is that African American men are resistant to insulin as a glucoregulatory hormone and resistant to insulin as a fat regulatory hormone. In contrast, African American women are resistant to insulin as a glucoregulatory hormone but sensitive to insulin as a fat regulatory hormone. The frequently sampled intravenous glucose tolerance test is used to measure insulin?s action as a glucoregulatory hormone. Unfortunately there is no index of insulin?s action as a fat regulatory hormone. Hence we are working on the development of this index by obtaining free fatty acids during the frequently sampled glucose tolerance test. Our goal is be able to do one test to obtain information about both actions of insulin. However, the development of an index of free fatty acid sensitivity to insulin during the frequently sampled intravenous glucose tolerance test involves sophisticated mathematical modeling and will need to be validated. As we work towards developing this index, we have studied sex differences in body fat content and distribution in African Americans. The distribution of body fat has a major impact on the interaction between insulin and body fat. We determined using serial slice computerized tomographic scans and dual X-ray absorptiometry (DXA) that there are sex differences in central body fat distribution in African Americans. These findings will be published in the American Journal of Clinical Nutrition in November 2002. In addition, we have found that beta cell secretion of insulin is impaired in obese glucose intolerant African American women and this work was published in Diabetes Care in 2001. Now we are concentrating on sex differences in the free fatty acid profile during the frequently sampled intravenous glucose tolerance test. It is the intent that this free fatty acid work through the complicated process of modeling will lead to the development of an index of free fatty acid sensitivity to insulin. The development of this index is required so the research hypotheses can be fully tested.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK047023-01
Application #
6673625
Study Section
(RHA)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Jo, Junghyo; Gavrilova, Oksana; Pack, Stephanie et al. (2009) Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth. PLoS Comput Biol 5:e1000324
Sumner, Anne E; Luercio, Marcella F; Frempong, Barbara A et al. (2009) Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach. Metabolism 58:220-5
Imoisili, Omoye E; Sumner, Anne E (2009) Preventing Diabetes and Atherosclerosis in Sub-Saharan Africa: Should the Metabolic Syndrome Have a Role? Curr Cardiovasc Risk Rep 3:161-167
Clarenbach, Jacob J; Vega, Gloria Lena; Adams-Huet, Beverley et al. (2007) Variability in postheparin hepatic lipase activity is associated with plasma adiponectin levels in African Americans. J Investig Med 55:187-94
Williams, Richard Allen; Gavin 3rd, James R; Phillips, Robert A et al. (2006) High-risk African Americans with multiple risk factors for cardiovascular disease: challenges in prevention, diagnosis, and treatment. Ethn Dis 16:633-9
Sumner, Anne E; Finley, Karl B; Genovese, David J et al. (2005) Fasting triglyceride and the triglyceride-HDL cholesterol ratio are not markers of insulin resistance in African Americans. Arch Intern Med 165:1395-400
Boston, Raymond C; Moate, Peter J; Stefanovski, Darko et al. (2005) AKA-Glucose: a program for kinetic and epidemiological analysis of frequently sampled intravenous glucose tolerance test data using database technology. Diabetes Technol Ther 7:298-307
Sumner, Anne E; Vega, Gloria L; Genovese, David J et al. (2005) Normal triglyceride levels despite insulin resistance in African Americans: role of lipoprotein lipase. Metabolism 54:902-9
Sumner, A E; Bergman, R N; Vega, G L et al. (2004) The multiphasic profile of free fatty acids during the intravenous glucose tolerance test is unresponsive to exogenous insulin. Metabolism 53:1202-7
Tulloch-Reid, Marshall K; Hanson, Robert L; Sebring, Nancy G et al. (2004) Both subcutaneous and visceral adipose tissue correlate highly with insulin resistance in african americans. Obes Res 12:1352-9

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