Pathobiology and Reversibility of Prediabetes in a Biracial Cohort

Obesity Clinical Trial

— PROP-ABC  

Official title:

Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02027571
• Other study ID #: IRB Number: 12-01970-FB
• Secondary ID: R01DK067269
• Status: Completed
• Phase: N/A
• Start date: October 2013
• Est. completion date: October 2018

Study information

• Verified date: October 2016
• Source: University of Tennessee
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 the hypothesis that the ability of intensive lifestyle intervention to reverse prediabetes and return people's metabolism back to normal is dependent on how long people have had prediabetes.

Description:

The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study is following an extant cohort of 376 initially normoglycemic African American and Caucasian offspring of parents with type 2 diabetes for an additional 5years. The subjects were enrolled between 2006 and 2009 and have been followed up to 2012, during which 10 have developed diabetes and 101 developed prediabetes, without evidence of racial disparities.

The objectives of PROP-ABC are to gain a fuller understanding of the natural history and predictors of early glucose abnormalities, determine the role of race during the second wave of glycemic progression, and to access 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. Participants with prediabetes and others who develop prediabetes during PROP-ABC will receive Intensive Lifestyle intervention (ILI).

We define duration of prediabetes as the interval from date of confirmed prediabetes to the date of initiation of ILI, stratified to 3 prediabetes intervals: a) <1 yr, b) 1 to <3 yr, c) 3-6 yr. The primary outcome measure is restoration of normal glucose regulation (fasting plasma glucose <100 mg/dl and 2-hour post-load plasma glucose < 140 mg/dl). Secondary endpoints include normalization of either fasting plasma glucose or 2-hour post-load plasma glucose , occurrence of diabetes, insulin sensitivity and secretion. Data will be analyzed according to the "intention to treat" principle. Based on power calculations, a sample size of 150 subjects (50/prediabetes interval) would allow detection of medium to large effect off ILI with ~85% power. Kaplan-Meier survival curves will be generated for the 3 prediabetes intervals, and log-rank test will be used to analyze the time to occurrence of primary outcome. The prospective PROP-ABC, designed to identify new cases of prediabetes as they occur, is uniquely placed to test the time dependency of reversibility of incident prediabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 223
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• As planned these studies will enroll interested persons from among the group of 376 subjects who participated in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study between 2006 and 2012. That group includes 267 women and 109 men; 217 are African Americans and 159 are Caucasians. At the time of initial enrollment into POP-ABC, these participants were selected for being nondiabetic offspring of parents with type 2 diabetes. Race and ethnicity was by self-report of non-Hispanic white or non-Hispanic black heritage, and their age range was 18-65 years at enrollment. No new subjects will be recruited into this established cohort. To be eligible for inclusion in the renewal study, subjects must be ambulatory, be in good general health, and must not be taking medications known to alter insulin sensitivity, insulin secretion, or body weight.

Exclusion Criteria:

• Exclusion criteria: Persons not enrolled in POP-ABC study; diagnosis of diabetes or use of any antidiabetic medication; medical conditions that preclude participation in physical activity; history of liposuction, surgical weight reduction; use of glucocorticoids, beta-blockers, thiazide diuretics (> 25 mg/day), or medication known to alter glucose metabolism. Women who are pregnant or become pregnant while participating in this study will have all testing procedures delayed until 12 months after delivery.

Related Conditions & MeSH terms

• Glucose Intolerance
• Obesity
• Prediabetes
• Prediabetic State
• Type 2 Diabetes

Intervention

Behavioral:
• Intensive Lifestyle Intervention (ILI)
ILI consists of weight loss ( > 10%); caloric reduction; physical activity (180 min/week); monthly visits for group counseling for 6 months, followed by quarterly visits; and meal replacements.

Locations

Country	Name	City	State
United States	Clinical Research Center, University of Tennessee Health Scienc Ctr	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
University of Tennessee	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (8)

Dagogo-Jack S, Edeoga C, Ebenibo S, Chapp-Jumbo E; Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Research Group. Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study: baseline characteristics of enrolled subjects. J Clin Endocrinol Metab. 2013 Jan;98(1):120-8. doi: 10.1210/jc.2012-2902. Epub 2012 Nov 1. — View Citation

Dagogo-Jack S, Edeoga C, Ebenibo S, Nyenwe E, Wan J; Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Research Group. 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. 2014 Jun;99(6):E1078-87. doi: 10.1210/jc.2014-1077. Epub 2014 Mar 14. — View Citation

Ebenibo S, Edeoga C, Ammons A, Egbuonu N, Dagogo-Jack S; Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Research Group. Recruitment strategies and yields for the Pathobiology of Prediabetes in a Biracial Cohort: a prospective natural history study of incident dysglycemia. BMC Med Res Methodol. 2013 May 10;13:64. doi: 10.1186/1471-2288-13-64. — View Citation

Edeoga C, Owei I, Siwakoti K, Umekwe N, Ceesay F, Wan J, Dagogo-Jack S. Relationships between blood pressure and blood glucose among offspring of parents with type 2 diabetes: Prediction of incident dysglycemia in a biracial cohort. J Diabetes Complications. 2017 Nov;31(11):1580-1586. doi: 10.1016/j.jdiacomp.2017.07.019. Epub 2017 Aug 2. — View Citation

Nyenwe E, Owei I, Wan J, Dagogo-Jack S. Parental History of Type 2 Diabetes Abrogates Ethnic Disparities in Key Glucoregulatory Indices. J Clin Endocrinol Metab. 2018 Feb 1;103(2):514-522. doi: 10.1210/jc.2017-01895. — View Citation

Owei I, Umekwe N, Mohamed H, Ebenibo S, Wan J, Dagogo-Jack S. Ethnic Disparities in Endothelial Function and Its Cardiometabolic Correlates: The Pathobiology of Prediabetes in A Biracial Cohort Study. Front Endocrinol (Lausanne). 2018 Mar 13;9:94. doi: 10 — View Citation

Owei I, Umekwe N, Provo C, Wan J, Dagogo-Jack S. 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. 2017 Jul 19;5(1):e000415. d — View Citation

Owei I, Umekwe N, Wan J, Dagogo-Jack S. Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms. Exp Biol Med (Maywood). 2016 Nov;241(17):1961-1967. Epub 2016 Jul 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incident prediabetes in observational cohort	Incident prediabetes, microvascular complications, endothelial function, ankle-brachial index, body composition, adiposity measures, FPG, 2hPG , A1c, adipo- and inflammatory cytokines (hsCRP, TNF-a, IL-1a, IL-6, resistin, leptin and adiponectin), metabolic syndrome and individual components (waist, BP, triglycerides, HDL cholesterol, FPG), metabolically healthy and unhealthy obese phenotypes, transaminases (surrogate for liver fat), diet (FHQ score) physical activity (MAQ and NHANES scores) and smoking history.	Up to 60 months
Primary	The primary outcome measure is restoration of normal glucose regulation	The primary outcome measure is restoration of normal glucose regulation (FPG <100 mg/dl and 2hrPG < 140 mg/dl).	Up to 60 months
Secondary	Glucose normalization	Secondary endpoints include normalization of either fasting plasma glucose or 2-hr OGTT plasma glucose levels, occurrence of diabetes, insulin sensitivity and secretion.	Up to 60 months