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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