African Americans (AA) have higher prevalence of type 2 diabetes and its associated complications when compared to whites. The reason for the racial discrepancy in the two American populations remains uncertain. Although obesity is more common in the AA, recent evidence indicates that this can not explain the racial disparity in the two groups. Several recent metabolic studies including those from our lab have demonstrated that nondiabetic blacks have greater insulin resistance and hyperinsulinemia. Because hyperinsulinemia has been associated with hypertension and cardiovascular diseases, which are also more common in the AA, we have postulated that AA could have accelerated disease. Secondly, it is possible that AA are more constitutively susceptible to adverse effects of diabetes and the associated hypertension, when compared to whites. Therefore, intervention and prevention approaches for type 2 diabetes are urgently needed. Thus, the aims of the present proposal are to: 1) reduce the insulin resistance and hyperinsulinemia, 2) improve glucose-dependent glucose disposal, 3) maintain or preserve beta cell insulin secretion and 4) determine the effect of reduction of hyperinsulinemia on lipids and lipoproteins and blood pressure in the AA at greater risk for type 2 diabetes. The study population will consist of Group 1 (n=40) healthy control subjects and Group 2 (n= 160) AA who are either first-degree relatives of patients with type 2 diabetes, patients with impaired glucose tolerance test, former gestational diabetic patients, and former diabetic patients in remission. Serial anthropometric, blood pressure and metabolic studies will be performed at yearly intervals for 5 years. The metabolic studies will include standard glucose tolerance test (OGTT), insulin sensitivity (S1) and glucose- dependent glucose disposal (S-G) by the minimal model method by Bergman et al. and basal hepatic glucose production (HGP). The AA subjects in Group 2 will be randomized to receive a) diet + placebo, b) diet + metformin, c) diet + troglitazone and d) diet + glipizide. The 3 antidiabetic medications will be administered in very low doses at breakfast daily. The endpoint of the study is to determine which therapeutic approach will be most efficacious, well tolerated and accepted with respect to preventing deterioration in the glucose control with subsequent development of IGT and diabetes in the AA population at greater risk for type 2 diabetes. The significance of the present study is to: 1) provide the first placebo- controlled, randomized pharmacologic study to delay and/or prevent type 2 diabetes and to determine which metabolic parameter is critically important in preventing or delaying the onset of the disease in the AA population at greater risk for type 2 diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK048127-02
Application #
2148226
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1994-07-01
Project End
1999-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Stakos, Dimitrios A; Boudoulas, Konstantinos D; Gaillard, Trudy R et al. (2013) Regional and overall aortic function in nondiabetic individuals with insulin resistance and normal glucose tolerance. J Clin Endocrinol Metab 98:4457-63
Gaillard, Trudy R; Schuster, Dara; Osei, Kwame (2012) Characterization of metabolically unhealthy overweight/obese African American women: significance of insulin-sensitive and insulin-resistant phenotypes. J Natl Med Assoc 104:164-71
Stakos, Dimitrios A; Schuster, Dara P; Sparks, Elizabeth A et al. (2007) Association between glycosylated hemoglobin, left ventricular mass and aortic function in nondiabetic individuals with insulin resistance. Eur J Endocrinol 157:63-8
Osei, Kwame; Gaillard, Trudy; Schuster, Dara (2007) Thiazolidinediones increase hepatic insulin extraction in African Americans with impaired glucose tolerance and type 2 diabetes mellitus. A pilot study of rosiglitazone. Metabolism 56:24-9
Osei, Kwame; Gaillard, Trudy; Cook, Charles et al. (2005) Discrepancies in the regulation of plasma adiponectin and TNF-alpha levels and adipose tissue gene expression in obese African Americans with glucose intolerance: a pilot study using rosiglitazone. Ethn Dis 15:641-8
Osei, Kwame; Gaillard, Trudy; Schuster, Dara (2005) Plasma adiponectin levels in high risk African-Americans with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. Obes Res 13:179-85
Stakos, D A; Schuster, D P; Sparks, E A et al. (2005) Long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance: double blind, prospective, randomised study. Heart 91:589-94
Osei, Kwame; Gaillard, Trudy; Kaplow, June et al. (2004) Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin secretion in high-risk African Americans with impaired glucose tolerance test and type 2 diabetes. Metabolism 53:1552-7
Osei, Kwame; Rhinesmith, Scott; Gaillard, Trudy et al. (2004) Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. Diabetes Care 27:1439-46
Stakos, Dimitrios A; Schuster, Dara P; Sparks, Elizabeth A et al. (2003) Long-term cardiovascular effects of insulin sensitizer troglitazone on non-diabetic individuals with insulin resistance: double blind, prospective randomized study. J Cardiol 41:183-90

Showing the most recent 10 out of 17 publications