Pathobiology and Reversibility of Prediabetes in a Biracial Cohort
| Status: | Completed |
|---|---|
| Conditions: | Obesity Weight Loss, Endocrine, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 10/17/2018 |
| Start Date: | October 2013 |
| End Date: | October 2018 |
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.
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.
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.
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.
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.
We found this trial at
1
site
Click here to add this to my saved trials
