What is Impaired Glucose Tolerance (IGT)?
People with IGT have blood glucose levels that are higher than normal but not yet diabetic. This condition is diagnosed using the oral glucose tolerance test (OGTT). After a fast of 8 to12 hours, a person’s blood glucose is measured before and 2 hours after drinking a glucose-containing solution.

• In normal glucose tolerance, blood glucose rises no higher than 140 mg/dl 2 hours after the drink.
• In impaired glucose tolerance (IGT), the 2-hour blood glucose is between 140 and 199 mg/dl.
• If the 2-hour blood glucose rises to 200 mg/dl or above, a person has diabetes.

DPP participants were overweight and had IGT. In addition, researchers selected volunteers with IGT whose fasting blood glucose levels were between 95 and 126 mg/dl since they were at higher risk to develop diabetes.

How does the fasting blood glucose test differ from the oral glucose tolerance test?
In the fasting blood glucose test, a person’s blood glucose is measured after a fast of 8 to 12 hours:

• A person with normal blood glucose has a blood glucose level below 110 mg/dl.
• A person with impaired fasting glucose has a blood glucose level between 110 and 126 mg/dl.
• If the fasting blood glucose level rises to126 mg/dl or above, a person has diabetes

The OGTT includes measures of blood glucose levels after a fast and after a glucose challenge. In 1997, an American Diabetes Association (ADA) expert panel recommended that doctors use the fasting blood glucose test to screen their patients for diabetes because the test is easier and less costly than the OGTT. Though the fasting glucose test detects most diabetes cases, the OGTT is more sensitive in identifying people with blood glucose problems that may first appear only after a glucose challenge.

For a person with IGT, what is the risk of developing type 2 diabetes?
As few as 1 to as many as 10 of every 100 persons with IGT will develop diabetes per year. The risk of getting diabetes rises as people become more overweight and more sedentary, have a stronger family history of diabetes, and belong to a racial or ethnic minority group. In the DPP, about 10 percent of participants in the placebo or standard group developed diabetes per year. The DPP interventions decreased the development of diabetes by 58 percent with intensive lifestyle interventions and by 31 percent with metformin.

How many people in the United States have IGT?
About 16 million people in the United States have IGT, according to the National Health and Nutritional Examination Survey III.

It is important to note that the interventions were effective in the setting of a controlled clinical trial in which volunteers randomized to lifestyle intervention received a great deal of individualized instruction. The Public Health Service and organizations such as the American Diabetes Association will review the results and consider a number of issues before making recommendations for the general population. For example, metformin is currently approved for treating, not preventing, type 2 diabetes. The Food and Drug Administration (FDA) would determine whether to make diabetes prevention an added indication for this drug. Another consideration is that, due to the risk of lactic acidosis, metformin should not be given to people with impaired kidney or liver function or to people who drink excessive amounts of alcohol. People for whom metformin might be harmful were excluded from the DPP.

How do the DPP results compare to the findings of other type 2 diabetes prevention studies?
Several studies in other cultures have examined the effects of intensive changes in diet and exercise in people at risk for type 2 diabetes. A study in Finland showed that diet and exercise resulted in a risk reduction similar to that shown in the DPP. The Finnish trial, however, did not study the effects of metformin nor did it examine the effects of lifestyle changes in specific subgroups by weight, age, or race/ethnicity. In addition, participants in the Finnish study were a fairly homogenous European population compared to DPP volunteers, who come from diverse age and ethnic groups. Cultural factors greatly influence lifestyle changes. It was important to show that type 2 diabetes can be prevented in U.S. minority populations that are at disproportionate risk.

How do diet and physical activity work to prevent diabetes?
Obesity and sedentary lifestyle are known to increase the risk of both insulin resistance and type 2 diabetes. Insulin resistance, a disorder in which target tissues--muscle, fat, and liver cells--fail to use insulin effectively, accompanies and usually precedes type 2 diabetes. With the onset of insulin resistance, the pancreas compensates by producing more insulin, but gradually its capacity to secrete insulin in response to meals falters, and the timing of insulin secretion becomes abnormal. Weight loss resulting from diet and increased physical activity may lower diabetes risk by improving the ability of muscle cells to use insulin and to handle glucose more efficiently.

What were the goals of DPP’s lifestyle intervention arm?
The goals were to:

• achieve and maintain a weight loss of 7 percent with healthy eating and increased physical activity
• maintain physical activity at least 150 minutes a week with moderate exercise, such as walking or biking.

What dietary advice did participants receive?
Participants were asked to lower fat to less than 25 percent of caloric intake. If reducing fat did not result in weight loss, a calorie goal was added. Participants received culturally sensitive training in diet, exercise, self-monitoring, goal-setting, and problem-solving. Participants took part in a 16-session core-curriculum during the first 24 weeks, then were seen individually or in groups at least every other month, and contacted by mail or phone on the alternate months. They were also invited to attend three group classes on healthy eating, physical activity, or behavioral topics that were offered each year, and to participate in periodic motivational campaigns with clinic competitions and group walking events.

Lifestyle intervention more effectively reduced diabetes risk than metformin. Within each arm, did certain groups of DPP participants benefit more from the intervention than other groups?
Lifestyle intervention worked in all of the groups, but it worked particularly well in people aged 60 and older, reducing the development of diabetes by 71 percent. This is an important and heartening discovery because as many as 20 percent of people aged 60 and older develop diabetes. Among those taking metformin, its effect in reducing diabetes risk was most pronounced in younger, heavier people--those 25 to 40 years old with a body mass index of 36 (about 50 to 80 pounds overweight).

Did the DPP volunteers in the lifestyle group benefit more from one lifestyle change than the other, e.g., more from exercise than from diet or vice versa?
The study wasn’t designed to examine the effect of exercise versus diet, so researchers can’t answer that question easily. However, they will perform secondary analyses that may provide some insight into this issue.

Lifestyle changes with diet and exercise reduced diabetes risk, as did treatment with metformin. By combining these interventions, could diabetes risk be reduced even further?
DPP researchers did not study the combination of lifestyle changes and metformin, so the joint effects of the two interventions are unknown.

Would the new formulation of metformin, Glucophage XR, be helpful to people with IGT?
The DPP researchers did not use Glucophage XR and therefore do not have any information about its potential value in preventing diabetes.

Do the DPP interventions affect the risk of cardiovascular disease, an important cause of mortality in people with type 2 diabetes?
DPP researchers are still analyzing the data and performing more studies to determine whether the interventions affected the development of atherosclerosis, which causes cardiovascular disease, or cardiovascular disease itself. These were important secondary outcomes in the study.

Are there any plans to get information about the DPP to the public and health care professionals?
The American Diabetes Association and NIDDK have a joint committee developing clinical recommendations for health care providers that will provide guidance on how the results of DPP can be applied to individual patients. The results of this work will be published in the next few months.

The National Diabetes Education Program (NDEP), a jointly sponsored initiative of the National Institutes of Health, the Centers for Disease Control and Prevention, and over 200 public and private organizations, has begun an effort to translate and disseminate messages and intervention strategies that derive from the DPP. The NDEP will be developing health messages and promoting diabetes treatment and prevention strategies for health professionals, people with diabetes and those at risk for the disease. This work is initially focused two areas: (1) developing and disseminating information and tools to help health care providers and people at risk for the disease to assess risk on an individual basis and (2) developing tools that health care providers and people at risk can use to attain and maintain the modest lifestyle changes that have been proven successful in preventing the onset of diabetes.

What is the estimated cost of the DPP interventions?
The DPP study group and PHS have been analyzing the cost effectiveness of the metformin and lifestyle interventions. Because the study ended early, these analyses are incomplete. The researchers hope to have an accurate estimate of the cost effectiveness or the cost benefit ratio for the interventions in the next six months.

Were there any deaths or serious injuries in the study resulting from metformin treatment or the lifestyle changes?
A total of 14 DPP participants died during the study. The rate of deaths was lower than the expected rate based on the overall U.S. population. Moreover, there were no significant differences between the number of deaths in the placebo, lifestyle, or metformin groups. None of the deaths was attributed to lifestyle changes or metformin.

Were there adverse effects associated with the interventions?
The only adverse effects linked to the interventions were diarrhea, which was reported more often by participants taking metformin, and musculoskeletal complaints associated with the lifestyle interventions.

What will happen to the volunteers who took part in the DPP?
The DPP researchers plan to continue following the DPP participants to learn more about the effects of these interventions on the development of diabetes.

What happened to the DPP volunteers who developed diabetes?
Those whose diabetes was well controlled with a fasting glucose of less than 140 mg/dl continued participating in the DPP and received advice on managing diabetes with their assigned intervention. If they needed other treatment, they were referred to their own physicians for further care.

Are diet and exercise beneficial even after diabetes develops?
Research has clearly shown that diet and exercise help people with type 2 diabetes control their blood glucose, blood pressure, and blood lipids in the short term. Although diet and exercise should lower the risk of developing cardiovascular disease and the other complications of diabetes, no long-term clinical trials have addressed this question. A recently launched trial, the Look AHEAD (Action for Health in Diabetes) study, will examine how diet and exercise affect heart attack, stroke, and cardiovascular-related death in people with type 2 diabetes.