Common Variation in Candidate Genes in the Diabetes Prevention Program

The Diabetes Prevention Program (DPP) was a multicenter controlled clinical trial examining the efficacy of an intensive lifestyle intervention or metformin to prevent or delay the development of diabetes in a population selected to be at high risk due to the presence of impaired glucose tolerance (IGT) and obesity. Development of diabetes, defined by 1997 American Diabetes Association (ADA) criteria, was the primary outcome while cardiovascular disease and its risk factors were important secondary outcomes. The pharmacological intervention was double blinded and placebo controlled. After randomization, participants had quarterly clinical evaluations and had, in addition, a fasting plasma glucose at semi-annual visits and a 75 gram oral glucose tolerance test at annual visits. Volunteers were recruited from populations known to be at particularly high risk for impaired glucose tolerance and type 2 diabetes including the following: persons with a family history of NIDDM, the elderly, overweight individuals, women with a history of diabetes during pregnancy ("gestational diabetes"), and minority populations including African Americans, Hispanic Americans, Asian and Pacific Island Americans, and Native Americans.

The primary focus of the genetic investigations have been on candidate genes, including candidates derived from GWAS of diabetes, lipid and glycemia-related phenotypes.

Please note more phenotype data for the DPPG cohort is available through the NIDDK Data Repository. Information on obtaining this phenotype data can be found by going to https://www.niddkrepository.org/studies/dppos/?query=DPP and https://www.niddkrepository.org/studies/dpp/?query=DPP. Data will need to be requested from both data sets. A linking file will be available to the NIDDK Data Repository.

• Study Weblinks:
  • Diabetes Prevention Program
• Study Design:
  • Clinical Trial
• Study Type:
  • Clinical Trial
  • Randomized
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 2535
• Subject Sample Telemetry Report (SSTR)

• BioSample
• Clinical Trials
  • NCT00004992
  • NCT00038727

In order to be eligible, persons who were older than 25 years with a body mass index ≥24 kg/m2 (≥22 kg/m2 in Asian-Americans) had demonstrated impaired glucose tolerance with plasma glucose levels 95-125 mg/dL (5.3-6.9 mmol/L) fasting and 140- 199 mg/dL (7.8 - 11.0 mmol/L) two hours after a 75 gram oral glucose tolerance test. Individuals with conditions or treatments that would interfere with participation in or completion of the protocol, or that have a confounding effect on the measurement of the primary outcomes of the study were excluded. A detailed list of inclusion and exclusion criteria can be found in http://www.bsc.gwu.edu/dpp/protocol.htmlvdoc.

The DPP began recruitment in mid-1996 and completed recruitment approximately three years later with a study cohort composed of 68% women, 45% minorities, and 20% ≥age 60. All 3,234 volunteers received standard lifestyle recommendations and were randomly assigned to one of three interventions: intensive lifestyle with the aim of losing and maintaining 7% weight loss and achieving > 150 minutes per week of moderate intensity physical activity, metformin therapy with 850 mg twice per day, or placebo. The troglitazone intervention in a fourth treatment arm (n=585) was discontinued in June 1998 because of the potential risk for severe liver toxicity that became apparent after the DPP was initiated. On the basis of a statistically significant and clinically compelling decrease in the development of diabetes in the lifestyle intervention and metformin-treated groups (58% and 31% reduction in hazards, respectively) compared with the placebo treated group, the DPP Data Monitoring Board and NIDDK ended the masked treatment phase of the study in August, 2001, one year earlier than originally planned.

• Primary Phenotype: Diabetes Mellitus, Type 2

• Principal Investigator
  • Jose Florez. Massachusetts General Hospital, Boston, MA, USA.
• Funding Source
  • RO1 -DK072041. NIDDK, National Institute of Health, Bethesda, MD, USA.