Intense
Diabetes Therapy Cuts Heart, Kidney Problems
Study Finds Careful
Management A Plus
Diabetes researchers
have found more evidence that aggressive treatment can prevent
- and sometimes reverse - problems that result from the disease.
Two new studies, one
adding to previous research and the other contributing
new knowledge, appear in the New England Journal of
Medicine (NEJM).
Some 17 million Americans
suffer from diabetes (90 percent have type 2 diabetes, 10 percent
have type 1) - 11.1 million have been diagnosed, but 5.9 million
are unaware they have the disease. Diabetes is the sixth leading
cause of death among Americans, and the fifth leading cause
of death from disease.
Diabetes is a metabolic
disorder characterized by a failure to secrete enough insulin,
or, in some cases, the cells do not respond appropriately to
the insulin that is produced. Because insulin is needed by the
body to convert glucose into energy, these failures result in
abnormally high levels of glucose accumulating in the blood.
The three main types
of diabetes - type 1, type 2, and gestational - are all defined
as metabolic disorders that affect the way the body metabolizes,
or uses, digested food to make glucose, the main source of fuel
for the body.
Type 1 diabetes is
an autoimmune disease in which the body's immune system destroys
the cells in the pancreas that produce insulin, resulting in
no or a low amount of insulin. People with type 1 diabetes must
take insulin daily in order to live.
Either type of diabetes
can cause blindness, kidney failure, amputations, heart disease,
and stroke.
Type
1 Diabetes Studied
Both of the new studies
look specifically at type 1 diabetes but, as an accompanying
editorial in the NEJM points out, results of
type 1 diabetes trials can, with certain limitations, be extended
to type 2 diabetes.
About a decade ago,
the landmark Diabetes Control and Complications Trial
(DCCT) found people with type 1 diabetes who tightly
controlled their blood glucose levels reduced the risk of eye,
nerve, and kidney complications by 35 percent to 76 percent.
The study participants were too young, however, to assess the
affect on atherosclerosis, or hardening of the arteries due
to plaque buildup.
The new trial, called
the Epidemiology of Diabetes Interventions and Complications
(EDIC), presents the good news that intensive diabetes
management can also reduce the risk of atherosclerosis in people
with type 1 diabetes.
The EDIC
trial involved 1,229 patients with type 1 diabetes who had also
been in the earlier DCCT trial. They were divided
into two groups: 611 who received conventional treatment and
618 who received intensive management.
The researchers used
ultrasound to measure the thickness of the wall of the participant's
carotid arteries at the beginning of the trial and, again, after
five years. The carotid arteries, located in the neck, carry
blood from the heart to the brain.
"We're measuring the
innermost layer and then the next layer in," says study author
Dr. David M. Nathan. "Those are the layers that are characteristically
affected by atherosclerosis, and it presages the development
of vascular disease."
After five years,
the thickness was significantly less in the diabetics who had
followed an aggressive glucose-management campaign during the
earlier trial.
"The group that was
treated intensively had a slower rate of progression," says
Dr. Nathan, director of the Diabetes Center at Massachusetts
General Hospital and a professor of medicine at Harvard Medical
School. "It appears that the advantage of therapy aimed at keeping
blood glucose levels as close to the nondiabetic range as possible
benefits not only diabetes-specific complications, but also
cardiovascular diseases."
Dr. Nathan pointed
out, however, that the regimen did not decrease heart attacks
or strokes. But the atherosclerosis measurement is "a well-recognized
surrogate marker" of disease. We were able to make a difference.
You need to apply this therapy as early as possible, and continue
to apply it."
The second study looked
at microalbuminuria, or the presence of protein in the urine,
which is the earliest sign of kidney disease.
Until now, conventional
wisdom held that kidney disease was inevitable in people who
had microalbuminuria. The best you could do was slow the progression
of a disease that would eventually lead, in one-third of patients,
to end-stage renal disease and dialysis or a transplant.
This study has found
that diabetics can do better than just slow down the disease.
"In the early stages,
it looks like the disease process can be reversed if patients
do the optimal things," says study author Dr. Bruce Perkins,
a fellow in endocrinology at the Joslin Diabetes Center in Boston.
"The important finding was that it does look like there is a
mechanism where the kidney can heal itself and, in fact, it
seems to do it quite often."
The authors looked
at 386 patients with type 1 diabetes and with microalbuminuria
that had been present for two years. The participants were followed
for an additional six years. At the end of that time, 58 percent
no longer had any protein leakage.
"People who do reverse
tend to have the lowest blood sugars, lowest blood pressure
and, most importantly, the lowest cholesterol levels," Dr. Perkins
says. "It seems likely that aggressive treatment is necessary
to reverse microalbuminuria."
Taking
a Proactive Approach
The first message,
then, is that screening is critical.
"Someone with diabetes
shouldn't allow years to go by without being screened for microalbuminuria
because if it's identified early, if we do the right things,
it can be reversed," Dr. Perkins says.
Physicians and patients
alike should perhaps also pay more attention to cholesterol
levels, including the possibility of taking cholesterol-lowering
drugs, although this should first be studied in a clinical trial,
experts say.
Always consult your
physician for more information.
Who
Should Be Tested for Diabetes?
The National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) states
that people over age 45 should be tested for diabetes. If the
first blood glucose test is normal, they should be re-tested
every three years.
People under age 45 should be tested for diabetes if they are
at high risk for diabetes based on these factors:
-
being more than 20 percent over ideal
body weight, or having a body mass index (BMI) of greater than
or equal to 27
-
having a first-degree relative with
diabetes (mother, father, or sibling) being a member of a high-risk
ethnic group (African-American, Hispanic, Asian, or Native American)
-
delivering a baby weighing more than
9 pounds, or having diabetes during pregnancy having blood pressure
at or above 140/90 mm/Hg having abnormal blood fat levels, such
as high-density lipoproteins (HDL) less than or equal to 35 mg/dL,
or triglycerides greater than or equal to 250 mg/dL (mg/dL = milligrams
of glucose per deciliter of blood)
-
having impaired glucose tolerance
when previously tested for diabetes
|
July 2003
Intense
Diabetes Therapy Cuts Heart, Kidney Problems
Type
1 Diabetes Studied
Taking
a Proactive Approach
Who
Should Be Tested for Diabetes?
Aging
May Affect Body's Ability to Ward Off Diabetes
Online
Resources
Aging
May Affect Body's Ability to Ward Off Diabetes
Power shortages in
the body's cells may contribute to insulin resistance and, eventually,
the development of type 2 diabetes in elderly people.
Researchers reporting
in the journal Science say that problems with
mitochondria, which are the cell's energy centers, may be at
the root of insulin resistance, which is a defining characteristic
of type 2 diabetes.
The discovery could
eventually lead to new drugs for type 2 diabetes, which is affecting
a growing number of Americans, particularly older ones.
"These advances are
very important for us to understand why certain things happen,"
says Dr. Edmund Giegerich, an endocrinologist and executive
vice president for medical affairs at Long Island College Hospital
in New York City.
"The application will
obviously come when someone can produce a medication that will
affect mitochondrial function," he says.
About 25 percent of
Americans over the age of 60 suffer from type 2 diabetes, which
occurs when the body's insulin fails to function properly.
Under normal circumstances,
insulin, a hormone produced by the pancreas, is responsible
for ushering glucose out of the blood stream after people eat.
Once glucose and fatty acids are safely inside the cell walls,
mitochondria convert them into energy through the process of
oxidation.
When insulin is not
doing its job, however, glucose remains in the blood stream
and, after prolonged periods of time, can result in such complications
as blindness and kidney failure.
Dr. Gerald I. Shulman,
senior author of the new study and a professor at Yale University
School of Medicine, had already discovered that an accumulation
of fat in muscle and liver tissue could lead to insulin resistance
in those same tissues.
The question he needed
to answer was what was behind the accumulation of fat. Shulman
believed the answer lay in one or both of two processes: that
fat cells were releasing more fatty acids than necessary or
there was a problem with the mitochondria's break-up of fatty
acids.
Shulman decided to
compare glucose and fatty acid metabolism in healthy elderly
people with young adults. The two groups were matched for lean
body mass as well as fat mass, so these factors could not affect
differences in insulin resistance.
The elderly participants
turned out to be more insulin-resistant, especially in muscle
tissue, than the younger participants. Magnetic resonance spectroscopy
revealed that the older group also had higher levels of fat
in the muscle tissue.
When the researchers
looked more closely, they discovered that the fat cells were
not releasing the extra fat building up in the muscle. In fact,
mitochondrial activity was reduced by about 40 percent in the
older group of participants.
"At least in the elderly,
it looks like it's mitochondrial dysfunction that leads to the
accumulation of fat inside the cells of muscle and livers,"
Shulman explains. "That then leads to insulin resistance through
pathways we've described previously.
"This really helps
pinpoint where one would now try to focus on improving mitochondrial
oxidative function," Shulman says.
Shulman also wants
to know if similar defects are occurring in the insulin-resistant
offspring of parents with type 2 diabetes.
"You can be in your
20s and be lean and have the same type of insulin resistance
as we're seeing in the elderly," he says. "They also have an
accumulation of fat in muscle and the same question exists:
Is it due to abnormalities in fat cells or defects in mitochondrial
function?"
Some good news is
that researchers have already shown that exercise can increase
the number of mitochondria. Until new medications are developed,
this study is yet another argument to get moving.
Always consult your
physician for more information.
Online
Resources
(Our Organization
is not responsible for the content of Internet sites.)
American
Diabetes Association
American
Heart Association
Centers
for Disease Control and Prevention (CDC)
Diabetes
Care
Healthier
US.Gov
National
Diabetes Education Program
National
Heart, Lung, and Blood Institute (NHLBI)
National
Institute of Diabetes & Digestive & Kidney Diseases
(NIDDKD)
National
Institutes of Health (NIH
New
England Journal of Medicine
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