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Metabolic Syndrome: A Useless Construct?

Birds of a feather flock together. As they investigated the risk factors for cardiovascular disease and diabetes, medical detectives observed that the usual suspects liked to hang out together. Obesity, high blood pressure, abnormal blood lipids, and elevated blood sugars regularly appeared together in the same patient. It looked like a syndrome that might boil down to one underlying cause. They called it “metabolic syndrome” and started applying the concept to clinical practice.

It seemed like a good idea at the time, but now skeptical scientists are expressing their doubts.

What Is Metabolic Syndrome?

A “syndrome” is defined as a group of symptoms and signs that together are characteristic of a specific disorder or disease. All syndromes are not created equal. Some syndromes are well-defined, with known causes, such as Down syndrome, a specific constellation of congenital abnormalities that can be confirmed by genetic tests demonstrating the presence of an extra chromosome (or related chromosomal abnormalities). Others are less well defined, like chronic fatigue syndrome, which consists of fatigue in association with a variable list of symptoms and signs like pain and enlarged lymph nodes. There is no lab test for it, the cause is not known, and the diagnosis itself is controversial.

Metabolic syndrome is a combination of factors that increase the risk of cardiovascular disease and diabetes. It’s also known by other names including syndrome X and insulin resistance syndrome. It has gotten a lot of press in recent decades, but some scientists have questioned whether it really exists. We know many risk factors for cardiovascular disease and diabetes, but when does a group of risk factors become a “syndrome” and when does it become useful for diagnosis, prevention, or treatment?

Metabolic syndrome is differently defined by different organizations. The worldwide consensus definition of the International Diabetes Federation requires central obesity plus any two of: raised triglycerides, reduced HDL cholesterol, elevated blood pressure, and increased fasting blood sugar. The World Health Organization requires diabetes or impaired glucose tolerance along with two of the following: HBP, dyslipidemia, central obesity, and microalbuminemia. The US National Cholesterol Education Program requires three of: central obesity, elevated triglycerides, decreased HDL cholesterol, elevated blood pressure, and elevated fasting blood sugar. The key feature is central obesity in one definition and diabetes in another, but neither is required at all in the third. This is disturbing, to say the least. A patient with elevated blood pressure, low HDL, and elevated triglycerides who is not obese or diabetic would be classified as having metabolic syndrome by the NCEP, but not by the IDF or the WHO!

And so the prevalence of this syndrome varies considerably depending on which definition is used. The overall prevalence of metabolic syndrome is around 25% in the US population. It varies by age and race, and is over 43% for those older than 65.

A New Study

A new study found that metabolic syndrome was associated with a two- to three-fold increased risk of MI, but the same risk was conferred by having either hypertension or diabetes alone. The authors said,

People who advocate for the metabolic syndrome concept believe that when the component risk factors occur together this would have an additive or greater effect on risk, and therefore it is important to identify these individuals. But we didn’t find that. So our study adds to the evidence that a diagnosis of metabolic syndrome is not useful. It is better just to treat the actual risk factors.

They pointed out that there is a dose-response relationship between risk-factor severity and MI risk and that a standard definition of metabolic syndrome loses information because it converts continuous variables into categorical variables. And there are other significant risk factors that metabolic syndrome fails to consider, like sedentary life style and smoking. It would make more sense to replace the categorical definition of metabolic syndrome with a scoring system that assigns a weight based on the level of each risk factor and that uses a regression formula.

A Joint Statement

This is not a new concern. Five years ago, the American Diabetes Association and the European Association for the Study of Diabetes issued a joint statement entitled “The Metabolic Syndrome: Time for a Critical Appraisal.” They reviewed the literature and concluded that

the metabolic syndrome has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and there is considerable doubt regarding its value as a CVD risk marker. Our analysis indicates that too much critically important information is missing to warrant its designation as a “syndrome.” Until much needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the “metabolic syndrome.

They acknowledged that the metabolic syndrome had been a useful paradigm for drawing attention to the fact that some CVD risk factors tend to cluster in patients. But now it is time for a

…serious examination of whether medical science is doing any good by drawing attention to and labeling millions of people with a presumed disease that does not stand on firm ground.

Conclusion

The concept of a metabolic syndrome originally seemed promising: it carried the hope of better identifying patients at risk, contributing to establishing an etiology related to insulin resistance, and determining better routes to prevention and treatment. These ideas haven’t panned out. It is still unclear whether obesity causes the associated findings or whether an underlying condition causes the obesity along with the other findings or whether something else is going on. It is becoming increasingly clear that identifying and managing individual risk factors is the way to go.

Should the concept of metabolic syndrome be abandoned? Probably. But human nature makes us reluctant to abandon any idea after it has rooted itself in our consciousness. The metabolic syndrome has become so well established in the popular medical mind that it will not go without a struggle.

Posted in: Science and Medicine

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