This proposal is in response to ProgramAnnouncement Number PA-04-074, """"""""Health Disparities inNIDDK Disease."""""""" In contrast to the widely reported ethnic differences in prevalence, the incidence of type 2 diabetes was surprisingly similar (~11%) among individuals from the different U.S. ethnic groups inthe Diabetes Prevention Program(DPP). Because DPP participants had impaired glucose tolerance (IGT) at baseline, the finding of similar incident diabetes rates led us to hypothesizethat ethnic disparities are initiated much earlier during the pathogenesis of type 2 diabetes than is commonly realized. We,therefore, propose to study ethnic disparities proximal to the stage of prediabetes (IGT and impaired fastingglucose {IFG}). We will compare the rates of progression from normal glucosetolerance (NGT) to prediabetes in 200 African-American and 200 Caucasian offspring of parents with type 2 diabetes. Compared with NGT subjects, persons with prediabetes (e.g., IGT) have a two-fold increased risk of fatal cardiovasculardisease (CVD). Yet, few prospective studies exist on the natural history, predictors, mechanisms, and mediatorsof progression from NGT to prediabetes in any population, and none in African-Americans. We arguethat focusing on this early period is of public health significance, because the IGT stage may already betoo late for complete reversal of metabolic and cardiovascular sequelae. In our proposed study, initially NGTsubjects at high risk for type 2 diabetes will undergo repeated metabolic assessments, including glucosetolerance, insulin sensitivity, beta cell function, adipocytokines, CVD risk markers,and socioeconomic and other pertinent endpoints for 5 years. DNAspecimens will be stored for future genetic analysis. The primary endpoint is progression from NGTto prediabetes. Secondaryendpoints include changes in caloricintake, physical activity, body composition, insulin sensitivity, insulin secretion, lipoproteins, adipocytokines, proinflammatory markers and other known or putative predictors of glycemic dysregulation. Bycomparing these endpoints between Progressorsand Nonprogressors and African-Americans vs. Caucasianswe hope to provide novel data on the natural history of prediabetes, and determine whether ethnic disparities are programmed during the transition from NGT to prediabetes. Increased understanding of the variousfactors that trigger the changefrom normal glucose to prediabetes would enable the discovery of early preventive interventions beforefull blown diabetes and its related complications become established. Furthermore, understanding howthese factors differ acrossethnic groups will improve our ability to better target preventive measuresin different communities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK067269-05
Application #
7794844
Study Section
Special Emphasis Panel (ZRG1-KNOD-N (01))
Program Officer
Staten, Myrlene A
Project Start
2006-04-01
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2010
Total Cost
$697,996
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Nyenwe, Ebenezer; Owei, Ibiye; Wan, Jim et al. (2018) Parental History of Type 2 Diabetes Abrogates Ethnic Disparities in Key Glucoregulatory Indices. J Clin Endocrinol Metab 103:514-522
Owei, Ibiye; Jain, Nidhi; Jones, David et al. (2018) Physiology of Glycemic Recovery and Stabilization After Hyperinsulinemic Euglycemic Clamp in Healthy Subjects. J Clin Endocrinol Metab 103:4155-4162
Brannick, Ben; Dagogo-Jack, Sam (2018) Prediabetes and Cardiovascular Disease: Pathophysiology and Interventions for Prevention and Risk Reduction. Endocrinol Metab Clin North Am 47:33-50
Nyenwe, Ebenezer A; Ogwo, Cherechi C; Owei, Ibiye et al. (2018) Parental history of type 2 diabetes is associated with lower resting energy expenditure in normoglycemic subjects. BMJ Open Diabetes Res Care 6:e000511
Ebenibo, Sotonte; Edeoga, Chimaroke; Owei, Ibiye et al. (2018) Basal and Dynamic Leptin Secretion: Association with Cardiometabolic Risk and Body Weight Trajectories in African-Americans and European-Americans. Front Endocrinol (Lausanne) 9:12
Owei, Ibiye; Umekwe, Nkiru; Provo, Casey et al. (2017) Insulin-sensitive and insulin-resistant obese and non-obese phenotypes: role in prediction of incident pre-diabetes in a longitudinal biracial cohort. BMJ Open Diabetes Res Care 5:e000415
Jiang, Yunna; Owei, Ibiye; Wan, Jim et al. (2016) Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) study. BMJ Open Diabetes Res Care 4:e000194
Brannick, Ben; Wynn, Anne; Dagogo-Jack, Samuel (2016) Prediabetes as a toxic environment for the initiation of microvascular and macrovascular complications. Exp Biol Med (Maywood) 241:1323-31
Owei, Ibiye; Umekwe, Nkiru; Wan, Jim et al. (2016) Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms. Exp Biol Med (Maywood) 241:1961-1967
Boucher, Andrew B; Adesanya, E A Omoluyi; Owei, Ibiye et al. (2015) Dietary habits and leisure-time physical activity in relation to adiposity, dyslipidemia, and incident dysglycemia in the pathobiology of prediabetes in a biracial cohort study. Metabolism 64:1060-7

Showing the most recent 10 out of 35 publications