"Our goal was to discover if we could effectively prevent or delay the onset of Type II diabetes for those at highest risk, and, if so, what was the best way to do that," says Dr. William Knowler, a coordinating investigator of the large, multi-center national trial headed by the National Institutes of Health (NIH).
That goal was met through the largest study ever of its kind -- one that took place at 27 sites around the United States.Conducted under the auspices of the Diabetes Prevention Program Research Group, researchers examined the effectiveness of two important diabetes treatments. The first is lifestyle modifications, primarily dietary changes and exercise, with weight loss being the goal. The second treatment is the medication metformin, a drug commonly used to treat Type II diabetes. The idea was to see if either one could work to prevent diabetes in high-risk patients, and if so, which might work best.
"We were pleased and happy to see that both interventions proved successful, although the lifestyle modification did yield better results," says Knowler.
According to diabetes expert Dr. Loren Wissner-Greene, this is a powerful study with far-reaching effects.
"It showed us that a major disease -- a major killer disease -- can be prevented, and the strategies are something that are available to almost everyone. Everyone can take steps to protect themselves from developing Type II diabetes, even those already showing signs of impending disease. It's just wonderful news," says Wissner-Greene, a professor of endocrinology at New York University Medical Center.
The study, published in tomorrow's New England Journal of Medicine, included 3,234 non-diabetics whose average age was 51. Sixty-eight percent of the participants were women; 45 percent were from minority groups.
Each was considered at high risk for diabetes, with a body mass index of at least 24 -- an indication of being overweight. And all had significantly elevated blood sugar levels both after fasting and two hours following ingestion of a high sugar solution. Elevated blood sugar levels is a well-regarded precursor for diabetes.
The people were randomly assigned to one of three groups. The first group was given a "lifestyle modification program" centered around weight loss. The second group took the medication and was advised to live a healthier lifestyle. The third group was given a placebo drug and also told to live a more healthy lifestyle.
The lifestyle modification program included a weight loss goal of at least 7 percent of total body weight, along with 150 minutes of exercise a week, consisting mostly of fast walking. The program was implemented with a 16-lesson curriculum taught one-on-one during the first 24 weeks of the study. During that time, most of the participants reached their weight goal -- an average loss of 15 pounds.
The medication arm of the trial included a twice-daily dose of 850 milligrams of metformin, whose brand name is Glucophage, a medication that helps the body better utilize insulin and is a standard treatment for Type II diabetes.
The progress of the participants was followed for an average of 2.8 years.
The final result: Both the lifestyle modification program and the medication worked to delay the onset of diabetes, although the lifestyle program was almost twice as effective.
When compared to the placebo group, 58 percent of those assigned to the diet-and-weight-loss group avoided developing diabetes, compared to 31 percent in the group taking the medication.
However, in at least two areas of the study -- the fasting blood sugar level and the hemoglobin level (a kind of "marker" that indicates potential damage to blood vessels) -- results were similar in both the lifestyle intervention and medication groups, Wissner-Greene points out.
Earlier studies in both China and Finland had found that both lifestyle modification and medication could reduce the risk of diabetes. But this is the first major trial to show that diet and exercise can delay diabetes in a diverse American population that's becoming increasingly overweight and running a higher risk of diabetes.
In sharp contrast, studies released last year found that taking insulin as a way of preventing the onset of Type I diabetes was not effective.
Type II diabetes -- also known as adult onset diabetes -- occurs when the body is unable to adequately use its own insulin supply to properly utilize sugars and carbohydrates. Although it differs from Type I diabetes, which affects the body's ability to manufacture any insulin, both forms of the disease result in similar complications. These include dramatically increased risks of heart disease, high blood pressure, kidney failure, blindness and limb amputation. According to the National Institutes of Health, up to 10 million adults have Type II diabetes.
Knowler notes that the study initially included a second medication known as troglitazone (brand name, Rezulin). But a link to liver toxicity forced this drug off the market shortly after the start of the trial. Although other, similar medications were still available, it was too late to include them in the trial.
In addition to not knowing whether the results would have changed with the addition of this second medication, Wissner-Greene also points out that it is also not known whether the results could have been any more powerful had there been a third group utilizing the combination of lifestyle modifications and medication.
Still, she says, the take-home message is clear: "Type II diabetes can be prevented, and the tools are available to everyone."
And she adds, "There are few killer diseases about which you can say that."