The Metabolic Syndrome

Current Issues

Reported by Joelle Escoffery, PhD

The Metabolic Syndrome—Pro

George Alberti, MD

There are numerous challenges associated with the metabolic syndrome, including:

In 1988, Reaven coined the term “Syndrome X,” which consisted of:

In the following 2 decades, definitions shifted to a focus on obesity, and in 1997, the metabolic syndrome was defined as a cluster of risk factors for diabetes and cardiovascular disease:

In 1999, the World Health Organization (WHO) attempted to describe and define the syndrome as follows:

At least 1 of the following:

At least 2 of the following:

The European Group for the Study of Insulin Resistance (EGIR) proposed the following definition:

Insulin resistance plus 2 or more of the following:

The Adult Treatment Panel III definition of metabolic syndrome included 3 or more of the following:

The numerous and conflicting definitions of the metabolic syndrome resulted in confusion. Accordingly, the International Diabetes Federation (IDF) published a consensus, the goals of which were to provide a clinically useful definition that allows for the identification of individuals at high risk for diabetes and cardiovascular disease (CVD). To accomplish this objective, the IDF convened a group of individuals with different views and established a working definition of the metabolic syndrome. IDF consensus included the following components: adiposity, elevated triglycerides, low HDL, elevated blood pressure, and dysglycemia. As their measure of adiposity, they selected waist circumference and created ethnicity-specific values. This working definition represents a good start, but further refinement of parameters and more outcome studies are needed.

Although the metabolic syndrome gives a measure of relative rather than absolute risk, it is associated with an increased risk of diabetes and CVD. The CVD risk takes many years to reveal itself, and current studies are not carried out far enough to observe this effect.

Overall, it is a useful way of focusing on subjects at high risk of CVD and diabetes, especially if examined in conjunction with other risk factors (eg, elevated LDL-C, smoking, family history). Although the IDF definition provides a good start, more research is needed to identify and define the best set of factors that comprise the metabolic syndrome.

Metabolic syndrome—Con

Richard Kahn, PhD

In terms of definitions of the metabolic syndrome, there is a new definition every 2 years, now totaling 7 definitions. Further, none of these new definitions have been accompanied by new data. Each definition has different cut points for the different criteria used, which greatly affects whether or not people meet the criteria for the syndrome. Another interesting problem with the various definitions is that some factors are required in certain definitions (eg, waist circumference in the IDF definition), and such an approach misses patients who might otherwise fit the definition. For example, in a study of all-cause mortality, waist circumference, and other metabolic syndrome components, people who do not meet the WHO requirement for waist circumference but have 2 of the other risk factors have an elevated risk of mortality. Conversely, patients with elevated waist circumference and fewer than 2 of the other factors defining the syndrome are also at increased risk of all-cause mortality.

In an effort to determine whether the best cut points for the various components of the metabolic syndrome are currently being used, a theoretical study using the Archimedes model of health and disease was performed. Results showed that sensitivity, specificity, and positive predictive value were poor. Although the components of the metabolic syndrome and cut points used will greatly impact sensitivity, specificity, and positive predictive value, very little research has examined this issue. Additionally, there are no criteria for adding another sign or symptom, although there is no shortage of candidates, including adiponectin, age, C-reactive protein, etc.

When attempting to use the metabolic syndrome to predict insulin resistance, the sensitivity measures again are less than optimal. When attempting to predict coronary events or hypertension, BMI is the strongest predictor; when predicting type 2 diabetes, waist:hip ratio is the strongest predictor. There is a strong relationship between insulin resistance and the components of the metabolic syndrome, but the metabolic syndrome is not a strong predictor of type 2 diabetes. In fact, IGT predicts type 2 diabetes just as well as the metabolic syndrome. Although there is an observed relationship between the metabolic syndrome and cardiovascular events, CVD risk factors define the syndrome, so such a finding is relatively unimpressive. The evidence suggests that the whole is no greater than the sum of its parts. When predicting diabetes and CVD, FPG is as strong a predictor and is easier to use than the metabolic syndrome. Using the definition of metabolic syndrome is also unlikely to confer any benefit when determining how to treat patients.

In conclusion, there is no rationale for the algorithms used to define the metabolic syndrome, and insulin resistance as the underlying factor is unlikely. Examining these factors as a syndrome confers no benefit and may lead to treatment confusion by detracting from the need to prioritize treatments and conveying a distinct disease when one may not exist. Its predictive value for diabetes and CVD and diabetes is modest at best, and there are better, easier, and more cost-effective ways to determine risk. FPG is as strong a predictor of diabetes and CVD. Alternatively, counting risk factors or using a risk calculator may be a more effective strategy. The metabolic syndrome appears to be an algorithm looking for a purpose.