Participants are being randomized for DPP
Study of patients with impaired tolerance starts
The recruitment has ended and the randomizing is under way for the largest clinical trial for the prevention of Type 2 diabetes in those at high risk for developing the disease.
The Diabetes Prevention Program (DPP) has an ambitious goal of using lifestyle changes and drug therapy to reduce by one-third the number of glucose-impaired patients who go on to develop Type 2 diabetes.
DPP researchers have targeted people at the highest risk of developing diabetes by recruiting those in impaired glucose tolerance, with at least 50% of the participants members of minority groups (African-Americans, Hispanics, Native Americans, Asian-Americans, and Pacific Islanders), 50% women, and 20% over age 65.
All participants in the DPP have been diagnosed with impaired glucose tolerance (IGT), defined as fasting plasma glucose of 95 to 125 mg/dl or a two-hour plasma glucose at 140 to 199 mg/dl.
"This is a very important group of individuals who have never been studied and many of whom we think we can prevent from converting to Type 2 diabetes," says Sanford Garfield, PhD. Garfield is project director for the DPP at the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK) of the National Institutes of Health in Bethesda, MD.
Garfield says recruiters at the 27 clinical settings across the United States have probably exceeded the target population of 3,000 patients and have at least met the goals for minority and gender. But because there was some difficulty recruiting elderly participants, The study may not get enough participants over 65 to represent 20% of the cohort.
The primary purpose of the study is to determine the effects of three separate intervention plans in preventing conversion to diabetes:
1. The first intervention is an intensive lifestyle intervention with a projected weight loss of at least 7% of body weight through a program of diet, exercise (at least 150 minutes per week) and behavioral modification counseling (psychotherapy).
2. The second intervention is to use standard lifestyle recommendations plus a placebo.
3.The third intervention type is standard lifestyle recommendations combined with metformin, beginning with 850 mg daily and increased to 850 mg twice daily.
A planned fourth intervention using standard lifestyle recommendations plus troglitazone was dropped last summer after a small percentage of patients using Rezulin began experiencing acute liver failure.
Secondarily, Garfield expects the DPP to produce data on cardiovascular disease and its risk factors, changes in glycemia, beta-cell function, insulin sensitivity, obesity, diet, physical activity, and health-related quality of life.
Do DCCT and UKPDS findings apply?
Garfield says the DPP is intended to translate earlier findings in favor of tight glucose control to the prevention of the disease in those at risk. The DCCT and the UKPDS showed tight glucose control prevents complications. Researchers say they expect the DPP will show that tight glucose control among those who are glucose impaired will delay or even prevent the onset of Type 2 diabetes.
The Diabetes Control and Complications Trial (DCCT), which ended in 1993, produced results on Type 1 diabetes that showed unequivocally that tight glucose control can prevent complications of the disease and the United Kingdom Prospective Diabetes Study (UKPDS) of 1998 showed the same results for Type 2 diabetes.
Ischemic heart disease, uncontrolled hypertension, and aortic stenosis were excluded from the study because of the requirement for increased physical activity. In addition, the DPP excludes patients with renal insufficiency or congestive heart failure because of their increased risk of lactic acidosis with metformin.
Pregnant and nursing women and those who intend to become pregnant during the program were also excluded because metformin has not been shown to be safe during pregnancy or nursing.
Most of the recruitment was aimed at participants 35 and older, Garfield says, although the lower age limit is 25 to include high-risk groups at a younger age, particularly Native Americans.
Prospective participants were recruited with series of interviews and examinations, including:
• prescreening telephone assessment interview;
• single glucose measurement;
• interview in which a medical history is taken;
• measurement of body mass index (BMI) and blood pressure;
• measurement of fasting plasma glucose;
• two-hour plasma glucose test;
• other laboratory tests including liver function, electrolytes, serum creatinine, plasma triglycerides, complete blood count, thyroid-stimulating hormone and urinalysis;
• run-in/behavioral trial to test compliance with pill taking and record keeping;
• clinical evaluation including history and physical examination;
• electrocardiogram to detect exclusion factors;
• pregnancy test and review of eligibility and, if eligible, referral for randomization.
Garfield says in those assigned to the standard lifestyle category, the time to developing diabetes is expected to be 6.5 per 100 person years, and in those in the intensive lifestyle and metformin interventions, the rate of developing diabetes is expected to be reduced by one-third to 4.33 per 100 person years.
[Sanford Garfield can be reached at (301) 480-3503.]
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