DPPT (Diabetes Prevention
Program Trials) The Results are in, For Real.
Diet and Exercise Dramatically Delay
Type 2 Diabetes:
Today, we can say
conclusively, that, yes, there is something we can do for prevention.
Individual Americans may not need to succumb to this modern epidemic. Type
2 diabetes is not inevitable, and the solution may be as simple as getting
up off the couch, and eating a healthier diet.
Just like the DCCT and the
UKPDS trials, the DPPT made the front page for one day.
Within a week, most will have forgotten what the study showed and
will still not exercise and change their diets.
As educators we need to have this information at the top of our
education programs and constantly remind them.
Again and again we are reminded by these studies that Diet and
Exercise can not only prevent the complications, but also prevent or delay
from getting diabetes, in the first place.
The American Diabetes
Association feels that there are 4 important elements that can be derived
from the results so far.
First is the central message,
that, once and for all, diabetes can be prevented. Both the lifestyle
intervention, and use of the diabetes medication metformin, worked; and
the lifestyle changes were even more effective than medication.
This gives health care
professionals additional reason, based on solid evidence, to help their
patients improve diet and increase their levels of physical activity.
Second, the interventions
worked equally well across the broad spectrum of racial and ethnic
diversity that is the face of America, and is the face of type 2 diabetes
in America. The Diabetes Prevention Program provides very solid proof that
we, with all our varied diets and lifestyles, can successfully prevent
type 2 diabetes.
Third, the DPP demonstrates
the value of the health care team approach to treating people who are at
high risk of developing diabetes. Just as it takes a team approach to
treat diabetes itself, so the DPP has shown us that it takes dietitians,
health educators, doctors and others, working together, to prevent
diabetes.
Fourth and finally, the DPP
offers hope to people at risk for diabetes, because the lifestyle changes
required are relatively modest. A 10-15 pound weight loss, and a half hour
a day of brisk walking, were remarkably effective in preventing diabetes.
At least 10 million Americans
at high risk for type 2 diabetes can sharply lower their chances of
getting the disease with diet and exercise, according to the findings of a
major clinical trial announced by HHS Secretary Tommy G. Thompson today at
the National Institutes of Health (NIH).
"In view of the rapidly
rising rates of obesity and diabetes in America, this good news couldn’t
come at a better time," said Secretary Thompson. "So many of our
health problems can be avoided through diet, exercise and making sure we
take care of ourselves. By promoting healthy lifestyles, we can improve
the quality of life for all Americans, and reduce health care costs
dramatically."
The same study found that
treatment with the oral diabetes drug metformin (Glucophage®) also
reduces diabetes risk, though less dramatically, in people at high risk
for type 2 diabetes.
Participants randomly assigned
to intensive lifestyle intervention reduced their risk of getting type 2
diabetes by 58 percent. On average, this group maintained their physical
activity at 30 minutes per day, usually with walking or other moderate
intensity exercise, and lost 5-7 percent of their body weight.
Participants randomized to treatment with metformin reduced their risk of
getting type 2 diabetes by 31 percent.
The findings came from the
Diabetes Prevention Program (DPP), a major clinical trial comparing diet
and exercise to treatment with metformin in 3,234 people with impaired
glucose tolerance, a condition that often precedes diabetes. On the advice
of the DPP’s external data monitoring board, the trial ended a year
early because the data had clearly answered the main research questions.
Smaller studies in China and
Finland have shown that diet and exercise can delay type 2 diabetes in
at-risk people, but the DPP, conducted at 27 centers nationwide, is the
first major trial to show that diet and exercise can effectively delay
diabetes in a diverse American population of overweight people with
impaired glucose tolerance (IGT). IGT is a condition in which blood
glucose levels are higher than normal but not yet diabetic. (See also Diabetes
Prevention Program: Questions & Answers.)
Of the 3,234 participants
enrolled in the DPP, 45 percent are from minority groups that suffer
disproportionately from type 2 diabetes: African Americans, Hispanic
Americans, Asian Americans and Pacific Islanders, and American Indians.
The trial also recruited other groups known to be at higher risk for type
2 diabetes, including individuals age 60 and older, women with a history
of gestational diabetes, and people with a first-degree relative with type
2 diabetes.
"Lifestyle intervention
worked as well in men and women and in all the ethnic groups. It also
worked well in people age 60 and older, who have a nearly 20 percent
prevalence of diabetes, reducing the development of diabetes by 71
percent. Metformin was also effective in men and women and in all the
ethnic groups, but was relatively ineffective in the older volunteers and
in those who were less overweight," said DPP study chair Dr. David
Nathan of Massachusetts General Hospital, Boston.
DPP volunteers were randomly
assigned to one of the following groups:
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intensive lifestyle
changes with the aim of reducing weight by 7 percent through a low-fat
diet and exercising for 150 minutes a week.
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treatment with the drug
metformin (850 mg twice a day), approved in 1995 to treat type 2
diabetes.
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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 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 to 85, with an average age of 51. Upon entry to 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 percent of the DPP standard group developed diabetes during the
average follow-up period of 3 years. In contrast, 14 percent of the diet
and exercise arm and 22 percent of the metformin arm developed diabetes.
Volunteers in the diet and exercise arm achieved the study goal, on
average a 7 percent--or 15-pound-- weight loss, in the first year and
generally sustained a 5 percent total loss for the study’s duration.
Participants in the lifestyle intervention arm received training in diet,
exercise (most chose walking), and behavior modification skills.
Can the interventions prevent
diabetes altogether? "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 population to learn how long the
interventions are effective." The researchers will analyze the data
to determine whether the interventions reduced cardiovascular disease and
atherosclerosis, major causes of death in people with type 2 diabetes.
"Every year a person can
live free of diabetes means an added year of life free of the pain,
disability, and medical costs incurred by this disease," said Dr.
Allen Spiegel, director of the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), which sponsored the DPP. "The
DPP findings represent a major step toward the goal of containing and
ultimately reversing the epidemic of type 2 diabetes in this
country."
Diabetes afflicts more than 16
million people in the United States. It is the main cause of kidney
failure, limb amputations, and new onset blindness in adults and a major
cause of heart disease and stroke. Type 2 diabetes accounts for up to 95
percent of all diabetes cases. Most common in adults over age 40, type 2
diabetes affects 8 percent of the U.S. population age 20 and older. It is
strongly associated with obesity (more than 80 percent of people with type
2 diabetes are overweight), inactivity, family history of diabetes, and
racial or ethnic background. Compared to whites, black adults have a 60
percent higher rate of type 2 diabetes and Hispanic adults have a 90
percent higher rate.
The prevalence of type 2
diabetes has tripled in the last 30 years, and much of the increase is due
to the dramatic upsurge in obesity. People with a BMI of 30 or greater
have a five-fold greater risk of diabetes than people with a normal BMI of
25 or less.
To date, the cost of the DPP
is $174.3 million. The DPP is funded by the National Institute of Diabetes
and Digestive and Kidney Diseases, the National Institute of Child Health
and Human Development, the National Institute on Aging, the National
Center on Minority Health and Health Disparities, the National Center for
Research Resources, the Office of Research on Women's Health, and the
Office of Behavioral and Social Science Research within the NIH.
Additional funding and support was provided by the Centers for Disease
Control and Prevention, the Indian Health Service, and the American
Diabetes Association. The study also is funded in part through a
Cooperative Research Development Agreement (CRADA) with Bristol Myers
Squibb. Other sources of corporate support include Merck and Company,
Merck Medco, Hoechst Marion Roussell, Lifescan, Slimfast, Nike, and
Health-O-Meter.
Diabetes Prevention Program
Questions
& Answers
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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.
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In normal glucose
tolerance, blood glucose rises no higher than 140 mg/dl 2 hours
after the drink.
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In impaired glucose
tolerance (IGT), the 2-hour blood glucose is between 140 and 199
mg/dl.
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If
the 2-hour blood glucose rises to 200 mg/dl or above, a person
has diabetes.
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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.
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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:
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A person with normal
blood glucose has a blood glucose level below 110 mg/dl.
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A person with
impaired fasting glucose has a blood glucose level between 110
and 126 mg/dl.
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If
the fasting blood glucose level rises to126 mg/dl or above, a
person has diabetes.
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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 U.S. have IGT? Would the DPP interventions benefit all of them?
About 20 million people in the U.S. have IGT, according to the
National Health and Nutritional Examination Survey III. However,
since DPP researchers studied the interventions only in people with
glucose levels in the upper half of the impaired glucose tolerance
range, the findings can only be strictly applied to the 10 million
people with similar glucose levels after an OGTT. However, many
researchers think it is reasonable to assume that millions more
people with IGT would also benefit from the DPP interventions.
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 recently published 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 might 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.
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What were the goals of DPP’s lifestyle intervention arm?
The goals were to:
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achieve and maintain
a weight loss of 7 percent with healthy eating and increased
physical activity
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maintain physical
activity at least 150 minutes a week with moderate exercise,
such as walking or biking.
Participants
received training in diet, exercise, and behavior modification from
case managers who met with each participant for at least 16 sessions
in the first 24 weeks and then monthly.
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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 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, will 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, and the general public.
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.
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