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

October 10, 2018 updated by: University of Tennessee

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

223

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Clinical Research Center, University of Tennessee Health Scienc Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The primary outcome measure is restoration of normal glucose regulation
Time Frame: Up to 60 months
The primary outcome measure is restoration of normal glucose regulation (FPG <100 mg/dl and 2hrPG < 140 mg/dl).
Up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose normalization
Time Frame: Up to 60 months
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incident prediabetes in observational cohort
Time Frame: Up to 60 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Tennessee

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Samuel Dagogo-Jack, MD, University of Tennessee Health Science Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2013

Primary Completion (Actual)

October 1, 2018

Study Completion (Actual)

October 1, 2018

Study Registration Dates

First Submitted

January 2, 2014

First Submitted That Met QC Criteria

January 3, 2014

First Posted (Estimate)

January 6, 2014

Study Record Updates

Last Update Posted (Actual)

October 15, 2018

Last Update Submitted That Met QC Criteria

October 10, 2018

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB Number: 12-01970-FB
  • R01DK067269 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Group data will be published after completion of study and analysis of results. Individual participant-level information will not be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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