Research
Study Promises Hope for New Treatments
A protein that is overproduced by fat cells in obese individuals
appears to promote insulin resistance, thus elevating the risk for diabetes,
heart disease, and early death, according to a study reported in the medical
journal Nature.
Public health officials say physical inactivity and poor
diet are catching up to tobacco as a significant threat to health. Currently,
about 35 percent of women and 31 percent of men are considered seriously overweight.
Obesity is a serious, chronic disease that can inflict substantial harm to
a person’s health.
Until now the particular protein the researchers studied,
known as retinol binding protein 4, or RBP4, had been known solely for its
innocuous role as a "transport vehicle," involved in the delivery of vitamin
A to healthy tissue.
Identifying RBP4's less benign function as an instigator
of insulin resistance may lead scientists towards new medical interventions
that focus on limiting secretion of the protein among obese patients at risk
for type 2 diabetes.
"We have found a molecule not previously known to have any
role in insulin action and demonstrated that this protein can contribute to
the development of diabetes by blocking the action of insulin," says study
co-author Dr. Barbara B. Kahn, chief of the division of endocrinology, diabetes,
and metabolism at Beth Israel Deaconess Medical Center in Boston.
According to American Diabetes Association estimates,
more than 18 million Americans have diabetes. About 90 percent of these patients
have type 2 diabetes, while the remainder have type 1 diabetes - a distinct
type which results from the body's inability to produce insulin altogether.
Type 2 diabetes develops as the result of insulin resistance,
a condition defined by the body's inability to properly utilize naturally produced
insulin for the breakdown of sugars, starch, and other glucose-rich foods into
energy. The resulting dangerous buildup of glucose and insulin in the blood
is also associated with a high risk for cardiovascular disease.
Noting that insulin resistance seems to go hand-in-hand
with reduced levels of the glucose transporter protein, the researchers studied
mice to look for a causal relationship between levels of RBP4 and other fat-cell
proteins.
After eliminating a range of alternate molecular options,
they observed that levels of glucose-carrying proteins fell as fat cell RBP4
production rose.
Further tests in both mice and humans confirmed that excess
production of RBP4 appears to promote a drop in the glucose-carrying proteins.
Insulin resistance, they conclude, might therefore be avoided
if RBP4 levels could be reduced and controlled.
"This opens up a whole new treatment possibility for preventing
or treating type 2 diabetes, and for stopping the progression from obesity
to diabetes," says Dr. Kahn.
Cathy Nonas, director of the obesity and diabetes program
at North General Hospital in New York City and spokeswoman for the American
Dietetic Association, is enthused about any research that might lead
to new medication targets.
But Nonas cautions that the best treatment for diabetes
is prevention.
"We all hope that with this research they might be able
to manage diabetes better and maybe even prevent diabetes from occurring as
a result of insulin resistance," says Nonas.
"But I think [Dr.] Kahn would agree that no matter what
we do, nothing will get around the need to change our environment and change
our lifestyle,” says Nonas. “It is very important to understand
diabetes. But we also need to keep our weight at a healthy level. That's probably
the best medicine of all."
Nonas emphasizes that many US adults and adolescents eat,
drink, and sit around too much - ignoring the need for routine exercise and
healthy diets.
"Nothing can replace the need to prevent obesity in the
first place," she explains. "Obesity is one of the major precursors of insulin-resistance.
So the need to have more physical activity and manage weight is something that
doesn't go away no matter what new treatments unfold."
Dr. Kahn suggests, however, that while lifestyle is always
at the heart of any battle against obesity and diabetes, it is equally important
to keep up the search for new treatment targets such as RBP4.
"I agree that drugs don't take the place of diet and exercise," says
Dr. Kahn. "But unfortunately there are also some genetic underlying causes
related to diabetes.
“There are many people in the world who have type
2 diabetes who are not obese,” he notes. “So we will also need
treatments in combination with diet and exercise to make everyone healthy."
Always consult your physician for more information.
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A new study reported in the Journal
of the American Medical Association confirms a link between diabetes
and heart failure and spotlights insulin resistance as a key player.
Insulin resistance is often a precursor to diabetes. Insulin
is a hormone that converts glucose, or blood sugar, into energy for cells.
In some people, however, the tissues stop responding to
insulin, leaving the body unable to use glucose properly, according to the American
Academy of Family Physicians.
It has been known that obesity increases the risk of congestive
heart failure, a potentially fatal condition in which the heart muscle weakens,
progressively losing the ability to pump blood, the researchers say.
"The previously described association between obesity
and subsequent congestive heart failure may be mediated largely by insulin
resistance," they say in the report.
The US Surgeon General has declared that overweight and
obesity have reached epidemic proportions in this country.
One in three US adults is overweight or obese and 15 percent
of children between the ages of six and 19 are overweight.
The study adds another dimension to the relationship between
diabetes and heart failure, comments Dr. Adi Mehta, an endocrinologist at
the Cleveland Clinic Foundation.
An earlier US study found that 32 percent of older men
with heart failure eventually developed diabetes, compared to only 18 percent
of men with normal hearts, Dr. Mehta says.
The most accepted theory for the link between the two
conditions starts with the knowledge that fat cells do not use insulin very
well, notes Dr. Mehta.
"As fat becomes more resistant to insulin, more free fatty
acids come into the circulation" [system], he explains.
"They are an alternative source of energy to glucose for
cells. Myocardium [heart tissue] that uses free fatty acids for fuel tends
to die at a higher rate," Dr. Mehta says.
The new study, conducted at Uppsala University in Sweden,
of 1,187 men aged 70 and older found that those with insulin resistance were
much more likely to develop congestive heart failure (CHF) than those whose
bodies responded properly to insulin.
One-hundred four of the men in the study developed congestive
heart failure (CHF) during 8.9 years of follow-up, the researcher report.
And "insulin resistance predicted congestive heart failure
incidence independently of diabetes and other established risk factors for
CHF.”
The new finding "is one more brick in the wall that says
we can no longer be as fat as we are," Dr. Mehta emphasizes. "Several things
must be done. One is taking early steps to prevent obesity."
But people who are already obese can limit the adverse
effects of added fat, even if they have trouble losing weight, simply by
exercising, he says.
"If you can improve physical activity in the obese population,
there is a very good possibility that obesity would not be as great a health
problem," Dr. Mehta says.
Always consult your physician for more information.
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