Diabetes Prevention Program (DPP)

[Badri]

This research on Diabetes Prevention was published in the New England Journal of Medicine in 2002. It is still very relevant and worth publicizing.

The Diabetes Prevention Program (DPP) was a major multicenter clinical research study aimed at discovering whether modest weight loss through dietary changes and increased physical activity or treatment with the oral anti diabetic drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in study participants. At the beginning of the DPP, participants were all overweight and had blood sugar levels higher than normal but not high enough for a diagnosis of diabetes—termed prediabetes.

The DPP found that participants who lost a modest amount of weight through dietary changes and increased physical activity sharply reduced their chances of developing diabetes. Taking metformin also reduced the risk, although less dramatically. The DPP resolved its research questions earlier than projected and, following the recommendation of an external monitoring board, the study was halted a year early.

DPP Study Design and Goals
In the DPP, participants from 27 clinical centers around the United States were randomly divided into different treatment groups. The first group, called the lifestyle intervention group, received intensive training in diet, physical activity, and behavior modification. By eating less fat and fewer calories and exercising for a total of 150 minutes a week, they aimed to lose 7 percent of their body weight and maintain that loss.

The second group took 850 mg of metformin twice a day. The third group received placebo pills instead of metformin. The metformin and placebo groups also received information about diet and exercise but no intensive motivational counseling.

A fourth group was treated with the drug troglitazone (Rezulin), but this part of the study was discontinued after researchers discovered that troglitazone can cause serious liver damage. The participants in this group were followed but not included as one of the intervention groups.

All 3,234 study participants were overweight and had prediabetes, a well-known risk factor for the development of type 2 diabetes. In addition, 45 percent of the participants were from minority groups-African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, or Pacific Islander-at increased risk of developing diabetes.

Type 2 Diabetes and Prediabetes
Type 2 diabetes is a disorder that affects the way the body uses digested food for growth and energy. Normally, the food one eats is broken down into glucose. The glucose then passes into the bloodstream, where it is used by the cells for growth and energy. For glucose to reach the cells, however, insulin must be present.

Most people with type 2 diabetes have two problems: insulin resistance—a condition in which muscle, liver, and fat cells do not use insulin properly—and reduced insulin production by the pancreas. As a result, glucose builds up in the blood, overflows into the urine, and passes out of the body, never fulfilling its role as the body's main source of fuel.

About 23.6 million people in the United States have diabetes. Diabetes is the main cause of kidney failure, limb amputation, and new-onset blindness in American adults. People with diabetes are more likely to develop and die from cardiovascular disease. Death rates for diabetics from heart disease and stroke is about two to four times higher than in non-diabetics.
Prediabetes also called impaired glucose tolerance is a condition in which blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes. Having prediabetes puts one at higher risk for developing type 2 diabetes. People with prediabetes are also at increased risk for developing cardiovascular disease.

We now know that a large number of people in the world have prediabetes and those with prediabetes are likely to develop type 2 diabetes within 10 years, unless they take steps to prevent or delay diabetes.

Who should be tested for prediabetes and diabetes?

The Risk Factors to Prediabetes are:
• severe obesity
• being physically inactive
• family history of diabetes
• certain ethnic groups - African American, American Indian, Asian American, Hispanic/Latino, or Pacific Islander
• women giving birth to a baby weighing more than 9 pounds
• gestational diabetes-diabetes first found during pregnancy
• high blood pressure-140/90 mmHg or above-(or being treated for high blood pressure)
• HDL - below 35 mg/dL
• triglyceride level above 250 mg/dL
• women with polycystic ovary syndrome
• In acanthosis nigricans, characterized by a dark, velvety rash around the neck or armpits

Those without risk factors should be tested at age 45.

If results are normal, testing should be repeated every 3 years. Doctors may recommend more frequent testing depending on initial results and risk status.

DPP Results
The DPP's results indicate that millions of high-risk people can delay or avoid developing type 2 diabetes by losing weight through regular physical activity and a diet low in fat and calories. Weight loss and physical activity lower the risk of diabetes by improving the body's ability to use insulin and process glucose. The DPP also suggested that metformin can help delay the onset of diabetes.

Participants in the lifestyle intervention group-those receiving intensive individual counseling and motivational support on effective diet, exercise, and behavior modification-reduced their risk of developing diabetes by 58 percent. This finding was true across all participating ethnic groups and for both men and women. Lifestyle changes worked particularly well for participants aged 60 and older, reducing their risk by 71 percent. About 5 percent of the lifestyle intervention group developed diabetes each year during the study period, compared with 11 percent of those in the placebo group.

Participants taking metformin reduced their risk of developing diabetes by 31 percent. Metformin was effective for both men and women, but it was least effective in people aged 45 and older. Metformin was most effective in people 25 to 44 years old and in those with a body mass index of 35 or higher. About 7.8 percent of the metformin group developed diabetes each year during the study, compared with 11 percent of the group receiving the placebo.

Further Analyses of DPP Data
One analysis confirmed that DPP participants carrying two copies of a gene variant, or mutation, that significantly increased their risk of developing diabetes benefited from lifestyle changes as much as or more than those without the gene variant.

Changes in diet and physical activity leading to weight loss are especially effective in helping reduce risk factors associated with both diabetes and cardiovascular disease, including high blood pressure and metabolic syndrome.
high blood pressure in DPP participants decreased in the lifestyle intervention group but increased in the metformin and placebo groups over time.
- triglyceride and HDL cholesterol levels also improved in the lifestyle intervention group.
- levels of C-reactive protein and fibrinogen—risk factors for heart disease—were lower in the metformin and lifestyle intervention groups, with a larger reduction in the lifestyle group.
- Women in the lifestyle intervention group who lost 5 to 7 percent of their body weight through dietary changes and exercise had fewer problems with urinary incontinence than women in the other study groups.

Conclusion
People at risk for developing diabetes can prevent or delay the onset of diabetes by losing a modest amount of weight through diet and exercise. DPP participants in the lifestyle intervention group reduced their risk of developing diabetes by 58 percent during the study.
DPP participants who took metformin also reduced their risk of developing diabetes, but not as much as those in the lifestyle intervention group.

[DurayCharles]

Thank you for your article on Diabetes Prevention Program
I am a 80 year old male who was diagnosed as pre-diabetic from my recent HbA1c results taken over the past 8months
The results ranged from 6.75% to 7.6%.
I was prescribed Metformin 500mg daily
From your article you state that Metformin was most effective in the age group 25 to 45years
For now my Random Blood Glucose is between 6.2 and 7.8. My post prandial is always below 9 depending on my meals
What advise can you offer me
Short History
Not overweight .....weight 82 kgm
Hypertensive
Chronic Lymphocytic Leukemia
Atrial Fibrillation
Residual Peripheral Myelopathy following removal of Spinal tumour ( Neurofibroma ) T8/9
Thanking you most kindly for your input

[Badri]

Hi Chil,

Good to see you on the Forum.

To start with I must tell you I am not an expert on Diabetes. However from all that I read I can tell you, you seem reasonably well controlled. Experts are of the view that for the older age group if the kidney function is satisfactory and you are able to tolerate metformin, you should continue with it. In anyone aged 80 and over if the HbA1c is maintained below 7.5 they feel it is OK. One of the dangers of treating diabetes in the elderly is the blood sugar dropping to low levels. Hypoglycemia is very dangerous in the elderly. Hyperglycemia will not cause sudden death but Hypoglycaemia will.

Lifestyle changes certainly help keep you going and regular exercise is a must.