Solving Metabolic Syndrome's Addition Problem

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Scientists are debating whether this syndrome's parts really add up to a greater combined health worry as whole. Here's what you can do now to reduce your risk, regardless.

YOUR DOCTOR MAY call it "metabolic syndrome" or "insulin resistance syndrome" or "Syndrome X." It sounds complicated, but it's frighteningly simple: As many as 47 million American adults have the symptoms--obesity, centered in the abdomen; low good cholesterol; high blood pressure; and high fasting glucose and triglyceride counts--that are widely seen as increasing the risk of heart disease and type 2 diabetes.

How bad do those symptoms have to be to become collectively dangerous? Figures vary by researcher or association, but the criteria from the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) are the most widely used. The NCEP says the presence of three or more of these factors adds up to what's most commonly called metabolic syndrome:

• A waist circumference of greater than 35 inches for women or 40 inches for men

• A fasting blood triglyceride level of 150 milligrams or higher

• A "good" cholesterol (HDL) level of less than 50 milligrams for women or 40 milligrams for men

• Blood pressure of at least 130/85

• A fasting glucose of at least 110 milligrams.

Adding Up to Trouble?
But there's now some debate about whether those risk factors pose any greater danger in combination than they do individually. In a joint paper published in the September issue of Diabetes Care and Diabetologia, the American Diabetes Association and European Association for the Study of Diabetes argue the "syndrome" needs more research and warn doctors against diagnosing or treating it as a separate malady at this time.

Such a diagnosis "misleads the patient into believing he or she has a unique disease," says Richard Kahn, PhD, the American Diabetes Association's chief scientific and medical officer. "What they really have are well-known cardiovascular risk factors. The combination of risk factors does not add up to a more significant or higher cardiovascular risk than the individual components."

That dovetails with the views of Gerald Reaven, MD. The Stanford University School of Medicine professor first described Syndrome X--the cluster of cardiovascular risk factors disease associated with insulin resistance--27 years ago and is a leading researcher in the field. While it's obviously important to diagnose type 2 diabetes so that it may be treated, "the additional clinical benefit from knowing whether or not the patient has the metabolic syndrome is not obvious," Dr. Reaven and a colleague wrote in a Diabetes and Vascular Disease Research issue last year. "… A patient with type 2 diabetes, hypertension, high plasma triglyceride and low high-density lipoprotein cholesterol would qualify for a diagnosis of the metabolic syndrome (by two groups advocating such diagnosis) … (but) the treatment paradigm for this patient would not have been any different if criteria for the metabolic syndrome had never been promulgated."

Still, groups as respected as the World Health Organization and the American Heart Association have backed the concept, linking it to increased risk of stroke and other heart diseases. The heart association and the National Heart, Lung and Blood Institute issued a statement in the wake of the diabetes groups' paper, arguing that metabolic syndrome is a real and growing health concern.

Paul F. Jacques, DSc, senior scientist and director of the nutritional epidemiology program at Tufts' Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA), says metabolic syndrome still may prove useful with respect to diet. "For example, since diet may affect more than one of the metabolic syndrome criteria, a composite outcome… may provide a more sensitive test of the effect of dietary factors, such as fiber, on insulin resistance and disease risk," Jacques says. He goes on to note that "relating diet to individual risk factors is much easier to interpret than defining incidence of the syndrome."

Nicola McKeown, PhD, a scientist also with the HNRCA, was among the authors of a 2004 article that proclaimed metabolic syndrome an identifiable and potentially modifiable risk state. McKeown agrees with the diabetes association, however, that "the existing definition for some risk factors is ambiguous and much more research is needed in terms of whether the cluster of risk factors denotes a greater risk than the individual components."

What Should You Do?
What's the best way to deal with the risk factors? Certainly, you should be under a doctor's care. Edward Saltzman, MD, of the HNRCA's Energy Metabolism Laboratory says: "The frequency of monitoring depends on if there is frank hypertension, dyslipidemia, diabetes, etc. versus milder abnormalities that qualify for (metabolic) syndrome but aren't treated. At minimum, a yearly followup would be advisable."

When cardiovascular disease and diabetes are both present, the heart, kidneys, eyes and nervous system may be damaged, and that damage is unlikely to be reversed. "So, control of the components of the syndrome for prevention is paramount," Dr. Saltzman says.

According to the American Heart Association, "The safest, most effective and preferred way to reduce insulin resistance in overweight and obese people is weight loss and increased physical activity."

The benefits of slimming down and stepping up activity can include lower blood pressure and better cholesterol numbers. It's important to remember to modify your diet so that you include more vegetables and fruits while keeping fats to at least 20% of your intake. That's right--while you still shouldn't overdo the fat, you shouldn't consume too little, either. Go below 20%, and generally it means you're eating more carbohydrates, which can mean higher triglyceride and blood glucose readings.

And the HNRCA's Jacques notes that the evidence is "very limited" today that a low glycemic index diet--including non-starchy grains, fruits, vegetables and dairy products--can affect weight gain or insulin sensitivity independent of other metabolic syndrome components.

Keep Moving!
Study after study shows it: Step up the intensity of your physical activity, and the risk factors associated with metabolic syndrome go down. "Being physically active clearly benefits (individuals), even if they are overweight," McKeown says.

The Centers for Disease Control and Prevention recently evaluated the key metabolic syndrome factors in 1,626 American adults. The subjects were asked to report the frequency and the duration of participation in 43 leisure-time physical activities of moderate or vigorous intensity, as well as the amount of time spent watching television or videos or using a computer. "People with metabolic syndrome spent significantly more time watching TV or using a computer than people without this syndrome," reports the center's Earl Ford, MD, MPH.

Two studies from the Cooper Institute indicate that even a moderate increase in physical activity can fight metabolic syndrome.

One study tracked for nearly six years 10,498 people who initially were free of metabolic syndrome. The Cooper researchers found that men who were moderately fit were at a 26% lower risk for metabolic syndrome, and the risk was 53% lower for those who were highly fit. The numbers for women were 20% and 63% respectively. The study was published in the American Heart Association journal Circulation.

"Low cardiorespiratory fitness is a strong and independent predictor of incident metabolic syndrome in women and men," says Michael J. LaMonte, PhD, director of Cooper's

Epidemiology Division. "Clinicians should consider the potential benefits of greater cardiorespiratory fitness in the primary prevention of metabolic syndrome, particularly among patients who have already begun to cluster metabolic syndrome components."

An earlier Cooper study, published in Obesity Research, found that women who were the least fit were the most likely to develop metabolic syndrome. Researchers tested 7,104 women between 1979 and 2000. The women were divided into five categories of cardiorespiratory fitness, based on a maximal treadmill exercise test. Only 2.3% of the fittest women had metabolic syndrome risk factors, compared with 19% of the least fit.

"Simply moving from the lowest fitness category to the next highest fitness category decreased the likelihood of having metabolic syndrome by nearly threefold," says Steve Farrell, PhD, the study's lead researcher. "This can be accomplished by just being moderately active for at least 30 minutes a day, and it doesn't have to be done all at once."

So while the experts debate whether there even is such a thing as "metabolic syndrome," if you've got signs of the risk factors clustered under that controversial label, don't wait for the issue to be settled. Together or separately, these factors represent real health threats. But the good news is that by watching what you eat, losing weight and--especially--stepping up your activity level, you can do something about it.

Not Just for Grownups
Metabolic syndrome's risk factors are reaching down into America's youth. A study of 163 college students, published in Diabetes Care, found that 27% were overweight, 6% were pre-diabetic and 10% had either high total cholesterol or low "good" cholesterol. The study, conducted by Terry T.K. Huang, PhD, a former research assistant at Tufts University's Friedman School of Nutrition Science and Policy, found that overweight students were nearly three times more likely to exhibit a component of metabolic syndrome than students of normal weight. "Colleges and universities will be an important setting for the monitoring and intervention of obesity and the metabolic syndrome in the future," Huang concluded.

What About Drug Therapy?
Researchers have found a biochemical basis for many of the factors related to metabolic syndrome. The factors in combination dramatically increase the chances of developing life--threatening illnesses, says David Mangelsdorf, PhD, professor of pharmacology and biochemistry at the University of Texas Southwestern Medical Center. Mangelsdorf was among the authors of a recent article on the subject that appeared in the New England Journal of Medicine.

For more than a decade, scientists have known about a protein called retinoid X receptor, or RXR, that can bind to other receptors to form molecular complexes that can control genes related to metabolism regulation. But only in the past five years has the importance of RXR and its partner receptors in metabolic syndrome been known, Mangelsdorf says. Several receptors already are targets of drugs used to treat some disorders associated with the syndrome; others are part of drug companies' research into treatments for related diseases such as atherosclerosis and cholesterol gallstone disease. That research is not yet complete, however, and Mangelsdorf adds that "drugs alone have rarely been the answer to the problems of metabolic syndrome."

Indeed, when a drug was stacked up against lifestyle changes in one study, lifestyle changes won. In the Annals of Internal Medicine, a Diabetes Prevention Program research group reported that a 7% weight loss and two and a half hours of exercise per week reduced the incidence of the syndrome by 41% in three years. Treatment with a drug called metaformin also was studied, but it reduced incidence of the syndrome by only 17%.

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