Diabetes 2b Free

Finally, researchers link inflammation to illness in overweight people...

2010-03-08T09:06:00.000-08:00

Researchers are beginning to understand the ways in which being overweight or obese contributes to a downward spiral of inflammation that can trigger heart disease, diabetes and other ailments.

Two recent papers help explain the connection. In one, published in the Journal of Clinical Investigation, researchers at the University of California-San Francisco and the Gladstone Institute found that specialized white blood cells exposed to large amounts of saturated fats became inflamed. When the researchers genetically engineered cells to be able to hold more fat, the inflammation didn't happen.

Another, from the Albert Einstein College of Medicine, shows the hormonal cascade caused by fat can contribute to heart disease by producing a protein that keeps blood clots from breaking down.

Those are just two of dozens of labs homing in on how fat can trigger diabetes, heart disease and more.

A new view of fat

Up until about 10 or 15 years ago, doctors thought of fat as just fat, a bunch of cells that stored energy.

That changed in 1994, when researchers at Rockefeller University in New York discovered that fat cells actually produce leptin, a hormone that controls hunger and fat burning.

Suddenly, fat went from being an inert bunch of grease to an important player in the endocrine system. It's now known that fat produces at least 20 proteins, many of them hormones.

Then in 2005, a group at Columbia University in New York showed that when rodents were fed a high fat diet or became obese, their fat tissues became inflamed. This launched a new effort to find the cause.

Normally, inflammation is healthy, a part of the body's fight against infections. But when it happens in response to obesity, it can contribute to numerous ills, such as fatty liver disease, type 2 diabetes and atherosclerosis, says Anthony Ferrante, a medical professor at Columbia whose research focuses on obesity's affects.

The inflammation appears to happen because macrophages, white blood cells that attack and eat infection, congregate in fat tissue.

Why is a mystery. "Are the fat cells getting big, bursting and then the macrophages are going in to clean up the mess? Or is it that the macrophages are killing the fat cells?" asks Carey Lumeng, a pediatrician who studies obesity and inflammation at the University of Michigan-Ann Arbor.

A few years ago, Ferrante's lab discovered that in lean people, only 5% of fat tissue is made up of macrophages, while in the severely obese it can be more than 50%.

And why do they cause an immune response? One hypothesis is that higher concentrations of fat could trigger macrophages to go into inflammatory mode.

Once there, the macrophages recruit "legions of their comrades into the tissue with the idea of setting up a focus of inflammation, as would be the case if there was some sort of infection," says Suneil Koliwad, a researcher at the Gladstone on the Journal of Clinical Investigation paper.

But unlike an infection, "where one either recovers or dies, there is no end to the insult that triggers the inflammatory response. The obese person remains obese and the insult and inflammatory trigger lingers on and on chronically," he says.

Here, inflammation doesn?t mean just swelling. It?s a complex set of biological responses in the tissue during which macrophages cluster and go to work wielding their chemical weapons.

When that happens, they shift from being simple eaters of dead cells to killers of foreign invaders. To do that killing, they bring out chemical weaponry, including cytokines. These are substances that carry signals between cells and can be used to attack and destroy infections.

Research into the cause

The hope is that current research might lead to ways to decrease the body's inflammatory response to the presence of too much fat. The researchers at Albert Einstein took healthy, overweight people and raised their free fatty acid levels. In response, the macrophages started to produce more of a protein that keeps clots from breaking down, says Preeti Kishore, an endocrinologist and author of the report in Science Translational Medicine.

This is bad news for anyone who has heart disease or who's had a heart attack. There you want the clots to break up — fast — so blood flow to the heart isn't limited. But in the obese, too much of the protein kept the clots in place.

In San Francisco, researchers did some nifty genetic engineering to see if the problem was the fat itself. They created macrophages that could simply store more fat, introducing them through bone marrow transplants.

This protected obese mice against the fat-induced inflammatory response, says Koliwad.He calls the research exciting because it gives them "the potential for a therapeutic target to examine" when it comes to the ravages of obesity-induced immune response.

The hope is that current research might lead to ways to decrease the body?s inflammatory response to the presence of too much fat.

Lumeng, a pediatrician, says that's especially important because of the high levels of obesity among American children. Recent research has shown that children as young as three-years-old have the same kind of inflammation markers that adults with heart disease have. Doctors "are very worried about this," and what these long-term obesity and inflammation will mean for the health of America's children as they age. With over a third of children overweight according to the Centers for Disease Control and Prevention, "we're talking about decades of inflammation," Lumeng says.

Diabetes Complications with Coronary Heart Disease

2010-02-12T07:38:00.000-08:00

People with diabetes are at a greatly increased risk of developing coronary heart disease (CHD). Over a 20-year period, women with diabetes were more than threefold as likely to die from CHD as were women without diabetes. Similar data exist for men. Several established risk factors for CHD appear to be favorably affected by the consumption of soy foods.

For example, soy protein modestly lowers serum levels of low-density lipoprotein cholesterol (LDL) by five percent, and triglycerides by seven percent, and modestly raises levels of high-density lipoprotein levels by three perscent. Each of these effects will reduce CHD risk. In fact, over the course of many years each 1 percent reduction in LDL reduces CHD risk by as much as 2-4 percent.37,38

There is also evidence that soy protein makes LDL less atherogenic and that the isoflavones in soy beans directly improve the health of the coronary arteries by improving systemic arterial compliance and vascular reactivity. More recent evidence suggests that soy protein may lower blood pressure.

Although the conflicting data in each of these areas prohibit firm conclusions, a prospective epidemiologic study of nearly 65,000 Shanghai women found that soy protein intake was associated with an 86 percent reduction in the risk of non-fatal myocardial infarction, lending support to the notion that soy exerts multiple coronary benefits.

Finally, full-fat soy foods, which are rich in the essential fatty acid linoleic acid, can help to lower serum cholesterol by displacing higher-saturated fat foods in the diet. Furthermore, the soy bean is one of the few good plant sources of the essential fatty acid, alpha-linolenic acid, an omega-3 fatty acid that has independent coronary benefits. Certainly, on the basis of the established and possible coronary benefits, isoflavone-rich soy protein-based foods warrant a role in heart-healthy diets.

Child Pre-Diabetes and Obesity Risks Death At Early Age Found In Study...

2010-02-11T14:52:00.000-08:00

A recent and rare study tracked thousands of children through adulthood found that the heaviest youngsters were more than twice as likely as the thinnest to die before age 55 from illness or a self-inflicted injury.

Pre-diabetes with youngsters were at almost double the risk of dying before 55, and those with high blood pressure were at some increased risk, also. But obesity was the factor that most closely associated with an early death, researchers said.

This study was published Thursday in The New England Journal of Medicine, frm analyzed data gathered from Pima and Tohono O’odham Indians, whose rates of obesity and Type 2 diabetes soared decades before weight problems became widespread among other Americans. It is one of the largest studies to have tracked children for several decades after detailed information on weight and risk factors like high cholesterol were gathered.

Nearly one in three American children is now considered to be either overweight or obese, and this week, the first lady, Michelle Obama, kicked off a campaign intended to end childhood obesity.

The new study analyzed data gathered about 4,857 nondiabetic American Indian children born between 1945 and 1984, when the children were 11 years old on average, and assessed the extent to which body mass index, glucose tolerance, blood pressure and total cholesterol levels predicted premature death.

By 2003, 559 participants had died, including 166 who died of causes other than accidents and homicides, like cardiovascular disease, infections, cancer, diabetes, alcohol poisoning or drug overdose and a large number who died of alcoholic liver disease, which the study’s authors suggested might be exacerbated by diabetes.

Adults who had the highest body mass index scores as children were 2.3 times as likely to have died early as those with the lowest scores, and those with the highest glucose levels were 73 percent as likely to have died prematurely.

“This really points a finger at impaired glucose tolerance, or pre-diabetes, in ways we have not seen before,” said Edward W. Gregg, who is with the diabetes branch of the Centers for Disease Control and Prevention, and wrote an editorial accompanying the article. “We’ve been aware that pre-diabetes in adults is related to a lot of adverse outcomes, but the relationship in youth has not been as clear. There are not as many long-term studies to document a risk factor like pre-diabetes in youth all the way to adult outcomes.”

The study found that high blood pressure in childhood was only a weak predictor of early death and high cholesterol was not associated with premature death, but experts suggested those factors were easier to control with medication.

And though the American Indian community is not representative of the nation’s population as a whole, Dr. Gregg said its experience was instructive because “they’ve tended to be just a decade or two ahead of the rest of the U.S. population” in obesity.