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New Diagnosis for Overweight

Major Risk Factors Add Up to 'Metabolic Syndrome'

By Rob Stein
Washington Post Staff Writer
Tuesday, February 8, 2005; Page A01

Germaine Savoy has known for years she needed to lose weight and figured she was in for another lecture when she went to see her doctor last week. She wasn't expecting to hear that she had some strange, ominous-sounding syndrome.

"I've always been petrified about hearing I had diabetes," said Savoy, 50, a civilian employee at Fort Detrick in Frederick who lives on Capitol Hill. "But I never thought about this. I never heard of this."

"I know it's time to do something," says D.C. resident Germaine Savoy, 50, who was recently told she has metabolic syndrome. (Dudley M. Brooks -- The Washington Post)

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Savoy has joined the growing number of Americans who are being told they have "metabolic syndrome," a diagnosis that has become alarmingly common, primarily because of the obesity epidemic. A syndrome is a collection of symptoms that make someone prone to disease.

The metabolic syndrome, probably caused by a fundamental malfunctioning of the body's system for storing and burning energy, is defined by having a cluster of risk factors such as elevated blood pressure, poor blood sugar control, high levels of fats in the blood called triglycerides and low HDL, or "good" cholesterol. Individually, each factor may not be highly dangerous, but together they appear to sharply boost the danger of major health problems, notably heart disease, diabetes and, possibly, certain types of cancer.

At least 64 million Americans -- nearly a third of adults age 20 and older -- probably meet the federal government's criteria for the syndrome, and the rate approaches 50 percent among the elderly. Mexican Americans and African American women appear to be especially prone. It also turns up in people who are not obese but have recently put on a lot of weight around their middles, and in an increasing number of overweight children.

"It's a huge medical issue," said Scott M. Grundy of the University of Texas Southwestern Medical Center in Dallas. "And it's just getting worse."

Most of these people have no idea they have the syndrome, and many experts say that unless steps are taken to aggressively identify and treat them, it is likely to spawn future epidemics of heart attacks, strokes, diabetes and other diseases, including sleep apnea, liver disease, and polycystic ovary syndrome, which can cause infertility and other problems.

"The world has moved from infectious disease being the major thing that kills us to this kind of chronic illness," said David M. Nathan of the Harvard Medical School. "It is really the public health issue for the next millennium."

Many aspects of the syndrome remain unclear and controversial. There are several competing definitions, and experts disagree about how dangerous it is and how intensively it should be treated. Some argue that the syndrome arbitrarily lumps together risk factors that doctors already recognize and treat. Combining them into a "syndrome" could prompt doctors to put patients on drugs too quickly or, paradoxically, delay treating patients who need therapy, critics say.

"Conceptually, it's a step backwards," said Gerald M. Reaven of Stanford University, who pioneered an early form of the concept. "And I think it has the real potential to bring about damage clinically."

But most experts consider the approach very useful. They say it is crystallizing thinking about how fat causes illness, motivating patients to lose weight and exercise, pushing doctors to identify and treat patients sooner, galvanizing researchers to decipher the underlying biological defects, and spurring the development of a new generation of more targeted drugs.

"It's emerged as a very important concept," said Daniel Porte Jr. of the University of Washington and the University of California at San Diego. "It's made people think about these problems in a new way."

Versions of the syndrome have been recognized for years, beginning in 1988, when Reaven coined the term "syndrome X" to describe a condition triggered by an inability to respond properly to insulin, which controls blood sugar levels. The World Health Organization and the National Institutes of Health produced their own definitions in 1998 and 2002, respectively, for what they called the "metabolic syndrome," emphasizing the risk of cardiovascular disease. But the idea remained relatively obscure until the obesity epidemic.

"One can see this as the quintessential way in which modern life, in which we are overfed and underexercised, becomes illness," said Daniel Einhorn of UC-San Diego. "This is how obesity becomes illness."

It is unclear exactly how weight gain may throw the metabolism out of sync in so many ways. But, contrary to the long-held notion that fat is an inert storage area for energy, scientists have discovered that fat tissue pumps out an array of chemical signals that affect almost every aspect of the body.

"At some point fat becomes toxic and cannot be stored safely," said Ronald M. Evans of the Salk Institute for Biological Studies in San Diego, who has identified a set of genes that may play an important role in the syndrome.

Fat accumulation in the abdomen, particularly in muscle and the liver, appears to be especially dangerous.

"That's probably the key factor in the development of the metabolic syndrome," said Gerald I. Shulman of the Yale University School of Medicine.

Whatever the fundamental causes, experts say the diagnosis is prompting increasing numbers of doctors to recognize patients at risk much earlier.

"If you meet the criteria, you need to run, not walk, to do something about it," said George L. Blackburn of the Beth Israel Deaconess Medical Center in Boston.

That is especially important because the syndrome can be found in people who are not necessarily obese and often feel fine.

"This can sit silent for 10 years," Blackburn said.

Experts disagree about how much the syndrome boosts the risk of serious illness beyond that of the separate risk factors. But some estimate it may give a person five times the risk of diabetes and more than double the risk of heart disease in the next decade. Evidence has also been accumulating that the syndrome heightens the danger of colon and prostate tumors and some other cancers.

The same combination of danger signs is increasingly showing up in the young, putting them at risk for Type 2 diabetes, which once almost exclusively affected adults, and probably making them vulnerable to developing heart disease much earlier in life, experts say.

"They are not dying yet of heart disease," said Sonia Caprio of the Yale University School of Medicine. "But instead of having it at 60, they'll probably have it in their forties."

In many cases, most of the symptoms can be reversed through dieting and exercise.

"It's almost as if obesity is the mother of all these things," said Arthur Frank of George Washington University.

But many people have a hard time losing weight, keeping it off and maintaining an exercise regimen. So doctors frequently also give patients drugs, such as standard cholesterol and blood pressure medications.

Some doctors take an even more aggressive approach, prescribing diabetes medicines that increase the body's sensitivity to insulin, such as Glucophage, Actos and Avandia.

"I'm a big believer in aggressive therapy," said Matthew Mintz of the George Washington University Medical Center, Savoy's doctor. "I'll always recommend diet and exercise, but I've seen these drugs work."

Some experts worry, however, that the diagnosis may lead doctors to rush too quickly to drug treatment without giving dieting and exercise a chance.

"At this point, it should be treated behaviorally," said Steven Haffner of the University of Texas Health Science Center in San Antonio. "I don't think at this point there's a reason to give drug therapy specifically for the metabolic syndrome. The studies just aren't there yet."

Others have the opposite concern, worrying the government's criteria are arbitrary and misleading. Doctors following the guidelines could miss patients who should be treated just because they have only two instead of the three risk factors required under the definition, or because their test results fall just outside thresholds in the guidelines.

"Each of these are risk factors that should be dealt with if they are abnormal," said Reaven, who believes insulin resistance is the key problem.

As the debate continues, the syndrome has prompted a flurry of research to develop new drugs specifically to treat it, and a number are undergoing testing.

"Right now we have this broad-brush approach. We treat each of these elements individually with lots of drugs. That may be the best we can do," Nathan said. "But the hope is that you could come up with a single drug that could treat the metabolic syndrome in all its features."

Savoy is still coming to terms with her new diagnosis. Depending on what her latest blood tests show, Mintz, her doctor, may recommend starting drugs immediately, along with finally getting serious about dieting and exercise.

"I know it's time to do something," said Savoy, who at 5-foot-4 weighs 263 pounds. "I'm going on vacation, but when I get back I know now I'll have to start all over again. I know I've got to do the right thing."

© 2005 The Washington Post Company


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