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Preventing the disease before it is too late

Not only do changes in diet and physical activity prevent or delay the development of diabetes, they actually help restore normal glucose levels in many people with impaired glucose tolerance.


Walking an average of 30 minutes a day five days a week, and a lower intake of fat and calories help to reduce diabetes incidence.

MILLIONS OF people at high risk for type 2 diabetes can delay and possibly prevent the disease with moderate diet and exercise, a major clinical trial has found. The same study found that the oral diabetes drug metformin (Glucophage) also reduces type 2 diabetes risk, although not as effectively as lifestyle changes. Researchers announced results of the trial, called the Diabetes Prevention Program (DPP), last August after ending the study a year early. The study results are reported in the New England Journal of Medicine.

"This research conveys a powerful message of hope to individuals at risk for type 2 diabetes, a painful, life-threatening disease that has been increasing along with obesity," said HHS Secretary Tommy G. Thompson. "By adopting a moderate, consistent diet and exercise program, many people with one or more of the risk factors for type 2 diabetes can stop the disease before it becomes irreversible."

The DPP compared three approaches — lifestyle modification, treatment with metformin, and standard medical advice — in 3,234 overweight people with impaired glucose tolerance (IGT), a condition in which blood glucose levels are higher than normal but not yet diabetic.

About 20 million people in the United States have IGT, which raises the risk of developing type 2 diabetes and cardiovascular disease. Once a person has type 2 diabetes, the risk of heart and blood vessel disease is even greater — 2 to 4 times that of people without diabetes.

Diet and exercise that achieved a 5 to 7 per cent weight loss reduced diabetes incidence by 58 per cent in participants randomised to the study's lifestyle intervention group. Participants in this group exercised at moderate intensity, usually by walking an average of 30 minutes a day five days a week, and lowered their intake of fat and calories.

Volunteers randomly assigned to treatment with metformin had a 31 per cent lower incidence of type 2 diabetes. Metformin lowers blood glucose mainly by decreasing the liver's production of glucose.

"Lifestyle intervention worked equally well in men and women and in all the ethnic groups. It was most effective in people aged 60 and older, who lowered the risk of developing diabetes by 71 per cent. Metformin was also effective in both sexes and in all the ethnic groups, but it was relatively ineffective in older volunteers and in those who were less overweight," said study chair Dr. David Nathan of Massachusetts General Hospital, Boston.

Both interventions lowered fasting blood glucose levels, but lifestyle changes more effectively lowered blood glucose levels 2 hours after a glucose drink. Also, about twice as many people in the lifestyle group compared to placebo regained normal glucose tolerance, showing that diet and exercise can reverse IGT.

"Not only did changes in diet and physical activity prevent or delay the development of diabetes, they actually restored normal glucose levels in many people who had impaired glucose tolerance," said Dr. Allen Spiegel, director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the part of the National Institutes of Health (NIH) that sponsored the study. "These findings bring us closer to the goal of containing and ultimately reversing the epidemic of type 2 diabetes in this country."

DPP volunteers were randomly assigned to one of the following groups:

* lifestyle modification with the aim of reducing weight by 7 per cent through a low-fat diet and exercising for 150 minutes a week.

* treatment with the drug metformin (850 mg twice a day), approved in 1995 to treat type 2 diabetes.

* a standard group taking placebo pills in place of metformin.

The latter two groups also received information on diet and exercise. A fourth arm of the study, treatment with the drug troglitazone (Rezulin) combined with standard diet and exercise recommendations, was discontinued in June 1998 due to the potential for liver toxicity.

DPP participants ranged from age 25-85, with an average age of 51. Upon entering the study, all had impaired glucose tolerance as measured by an oral glucose tolerance test, and all were overweight, with an average body mass index (BMI) of 34. About 29 per cent of the DPP standard group developed diabetes during the average follow-up period of 3 years. In contrast, 14 per cent of the diet and exercise arm and 22 per cent of the metformin group developed diabetes.

Volunteers in the diet and exercise arm met the study goal, on average a 7 per cent — or 15-pound — weight loss, in the first year and generally sustained a 5 per cent total loss for the study's duration. Participants in the lifestyle intervention arm received training in diet, exercise (most chose walking), and behaviour modification skills.

Forty-five per cent of DPP participants were from minority groups that suffer disproportionately from type 2 diabetes: African Americans, Hispanic Americans, Asian Americans, Pacific Islanders, and American Indians.

The trial also recruited other groups at higher risk for type 2 diabetes, including individuals aged 60 and older, women with a history of gestational diabetes, and people with a first-degree relative with type 2 diabetes.

Can the interventions prevent diabetes completely? "We simply don't know how long, beyond the 3-year period studied, diabetes can be delayed," says Dr. Nathan. "We hope to follow the DPP volunteers to learn how long the interventions are effective." The researchers will analyse the data to determine whether the interventions reduced cardiovascular disease and atherosclerosis, major causes of death in people with type 2 diabetes.

Other studies have shown that diet and exercise delay type 2 diabetes in at-risk people. However, the DPP, conducted at 27 centres nationwide, is the first major trial to show that lifestyle changes can effectively delay diabetes in a diverse population of overweight American adults with impaired glucose tolerance.

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