Pathobiology and Reversibility of Prediabetes in a Biracial Cohort
Condition: Prediabetes; Type 2 Diabetes; Obesity
MeSH terms: Prediabetic State; Glucose Intolerance
Study type: Interventional

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.
    

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.
    

Intervention name(s): Intensive Lifestyle Intervention (ILI)
Intervention type(s): Behavioral
Intervention description(s): 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Diabetes; Race/Ethnicity; Offspring Cohort; African Americans; Prediabetes Reversal; Lifestyle Intervention; Insulin Sensitivity; Beta-cell Function; Diabetes Prevention