The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study proposes to study an extant cohort, comprising ~400 normoglycemic African American and Caucasian offspring of parents with type 2 diabetes for an additional 5-year. The subjects were enrolled between 2006 and 2009 and have been followed up to 2012, during which 11 have developed diabetes and 100 developed prediabetes, without evidence of racial disparities. The objective of the present proposal is to gain a fuller understanding of the natural history and metabolic predictors of early glucose abnormalities, by assessing the role of race during the second wave of glycemic progression, and the time dependency of reversibility of prediabetes. The study tests 4 hypotheses: 1) Among offspring of parents with type 2 diabetes, early progression from normal to impaired glucose regulation (within 5 yr) occurs in the highest-risk subjects independently of race, whereas late progression (5-10 yr) displays racial disparities, and is predicted by physiological, biochemical and behavioral markers;2) Early microvascular complications, peripheral vascular disease (PVD), and endothelial dysfunction manifest during transition from normal to impaired glucose regulation, display racial disparities, and are predicted by glycemic and nonglycemic factors;3) The "metabolically healthy" insulin-sensitive obese (ISO) phenotype displays racial disparities in its association with cardiometabolic risk factors and incident dysglycemia among African-Americans and Caucasians offspring of parents with type 2 diabetes;and 4) Duration of the prediabetic state is a major determinant of, and is inversely related to, the efficacy of lifestyle intervention to induce regression of the prediabetic phenotype and restoration of normal glucose regulation. The 100 participants with prediabetes will receive Intensive Lifestyle intervention (ILI), to reverse prediabetes and restore normoglycemia. The ~260 participants who have maintained normal glucose status will continue follow-up for 5 years;persons who develop prediabetes will immediately receive ILI. Understanding the predictors of the escape from normoglycemia, the role of race, and the reversibility of new-onset prediabetes is of utmost importance, because the discovery of interventions for reversal of prediabetes will also help eliminate ethnic disparities in downstream diabetes events. The additional 5 years of follow-up will provide data on 10-yr rates and predictors of incident prediabetes, racial patterns during the second wave of progression, and, time-dependent reversibility of prediabetes. Focusing on prediabetes is of immense public health significance, as its successful reversal prevents diabetes and associated complications.

Public Health Relevance

The reasons for the epidemics of diabetes and prediabetes, and why individuals from certain populations suffer at higher rates are not well known. In the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study, nearly 400 African Americans and Caucasians whose parents have type 2 diabetes will undergo repeated testing to determine what factors lead to the occurrence of prediabetes, and whether race still plays a major role in a setting where everyone being studied has one or both parents with diabetes. The PROP-ABC Study also will test whether proper nutrition, increased physical activity, and maintaining healthy weight soon after the occurrence of prediabetes will return people's metabolism back to normal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK067269-06A1
Application #
8580480
Study Section
Special Emphasis Panel (ZRG1-EMNR-T (02))
Program Officer
Bremer, Andrew
Project Start
2004-04-01
Project End
2018-05-31
Budget Start
2013-09-18
Budget End
2014-05-31
Support Year
6
Fiscal Year
2013
Total Cost
$652,004
Indirect Cost
$217,335
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
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
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
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
Dagogo-Jack, Samuel (2015) Philip E. Cryer, MD: Seminal Contributions to the Understanding of Hypoglycemia and Glucose Counterregulation and the Discovery of HAAF (Cryer Syndrome). Diabetes Care 38:2193-9
Ebenibo, Sotonte; Edeoga, Chimaroke; Wan, Jim et al. (2014) Glucoregulatory function among African Americans and European Americans with normal or pre-diabetic hemoglobin A1c levels. Metabolism 63:767-72
Dagogo-Jack, Samuel; Edeoga, Chimaroke; Ebenibo, Sotonte et al. (2014) Lack of racial disparity in incident prediabetes and glycemic progression among black and white offspring of parents with type 2 diabetes: the pathobiology of prediabetes in a biracial cohort (POP-ABC) study. J Clin Endocrinol Metab 99:E1078-87
Ebenibo, Sotonte; Edeoga, Chimaroke; Ammons, Ann et al. (2013) Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC): retention strategies. Diabetes Care 36:e50-1
Awoniyi, Omodele; Rehman, Rabia; Dagogo-Jack, Samuel (2013) Hypoglycemia in patients with type 1 diabetes: epidemiology, pathogenesis, and prevention. Curr Diab Rep 13:669-78
Garber, Alan J; Blonde, Lawrence; Bloomgarden, Zachary T et al. (2013) The role of bromocriptine-QR in the management of type 2 diabetes expert panel recommendations. Endocr Pract 19:100-6

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