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
Online
Resources
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
|
July 2003
In
This Issue:
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
Other
Resources:
Find
a St. John's Mercy Physician
Diabetes
Services at St. John's Mercy
Diabetes
Health Information
St.
John's Mercy Classes and Programs
In
Other Diabetes Health News:
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.
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