Evidence-Based Diabetes Management

The Controversial Question of Metabolic Syndrome

Published Online: April 11, 2013
The high prevalence of diabetes and cardiovascular disease (CVD) has tasked the medical community to not only treat but to better identify people at risk for these diseases. Risk factors for diabetes had been identified more than 90 years ago, and the term metabolic syndrome emerged in the late 1970s.1,2 In the late 1980s, a potential link had been identified—insulin resistance, which itself has been strongly associated with obesity.3 On the other hand, some believe that insulin resistance contributes to the development of the risk  actors but is not the underlying cause.4 Identifying a cluster of predictive risk factors would enable healthcare providers to identify and  treat patients with metabolic syndrome, thus reducing the risk for a progression to diabetes, CVD, or both.

The Controversy: What Is Metabolic Syndrome, and Is It a Treatable Disorder?

Metabolic syndrome (sometimes referred to as “syndrome X” or “insulin-resistance syndrome”) is defined as a grouping of several related risk factors,4 including:

• Abdominal fat

• Dyslipidemia

• Hyperglycemia

• Hypertension

Merriam-Webster defines the term syndrome as “a group of signs and symptoms that occur together and characterize a particular  abnormality.”5 What is truly more important to the final objective of preventing diabetes and CVD—identification of the underlying mechanism(s) for the syndrome, or identification of the risk factors that occur together and usually lead to diabetes and CVD?

This question defines the debate within the healthcare community: Is metabolic syndrome a cluster of risk factors or a syndrome? Proponents for  characterizing metabolic syndrome as a syndrome believe that the evidence linking the risk factors with the development of diabetes and CVD supports the view that it is a treatable entity. Detractors believe that metabolic syndrome is really just a clustering of risk factors, without any known underlying mechanism  that associates the maladies. Confounding the discussion is whether metabolic syndrome is a pre-morbid condition—whether metabolic syndrome can only  be recognized before a patient is given a diagnosis of diabetes or CVD, thus excluding the population with these highly prevalent chronic conditions. On the other hand, an actual diagnosis of diabetes or CVD does not affect the underlying mechanism (eg, insulin resistance or some other factor still exists).

Regardless of whether  professional organizations are supporters or skeptical of metabolic syndrome, the medical community as a whole believes that additional research is needed to better understand its etiology.

In 2005, the American Diabetes Association and the European Association for the Study of Diabetes published a statement underscoring their concerns regarding metabolic syndrome.6 Their concerns included the value of including diabetes in the definition, whether the criteria have accurate thresholds and are completely explanatory, and the omission of other cardiovascular disease risk factors. They worried that if the cardiovascular risk for metabolic  syndrome is the same as the sum of the individual risk factors, treatment of the syndrome would be the same as the treatment for each of the respective risk  factors. Furthermore, these professional societies were not convinced that insulin resistance is the unifying mechanism and whether there is overall value in  diagnosing the syndrome.

Yet, 2 American professional organizations and several international societies generally agree on the risk factors that should be included in the definition of  metabolic syndrome. Until this time, there were several different criteria discussed for metabolic syndrome, most notably from the World Health Organization, the National Cholesterol Education Program Adult Treatment Panel III, the International Diabetes Foundation, and the American Heart Association/National Heart, Lung, and Blood Institute. These organizations agreed on the risk factors that should be included in a definition of metabolic syndrome; however, they differed on the definition of the components and the number of risk factors that needed to be present to constitute the diagnosis. Members from these  organizations came together in 2009 to meld together consistent criteria for metabolic syndrome.4 Most disagreement involved whether body mass index or  waist circumference should be used as the indicator for central obesity. They concluded that waist circumference was a useful screening tool and should  correlate with specific country or population demographics, and that further research was required.

This coalition of professional societies did agree that having 3 of the abnormal findings from the cluster of 5 maladies would constitute a diagnosis of  metabolic syndrome (Table 1). They also agreed that people with any of the identified risk factors usually also present with a prothrombotic and proinflammatory state.

Obesity and physical inactivity have been found to be important contributors to metabolic syndrome.7 Other contributing factors include genetic and racial composition, aging, and the presence of other endocrine disorders. Patients with metabolic syndrome are usually susiceptible to additional problems as well, some that may be associated with its individual component risk factors:

• Fatty liver

• Cholesterol gallstones

• Obstructive sleep apnea

• Gout

• Depression

• Musculoskeletal disease

• Polycystic ovarian syndrome8

The Prevalence of Metabolic Syndrome

Assuming one accepts the definition of metabolic syndrome, it is unsurprising that its prevalence has increased over  time, perhaps reflecting the obesity  epidemic and predictions of greater incidence of diabetes.9 An analysis of the 2003 to 2006 National Health and Nutrition Examination Survey revealed  that, based on a waist circumference threshold of ≥102 cm for men and ≥88 cm for  women, the age-adjusted prevalence of metabolic syndrome in American adults was 34.3% (36.1% for men; 32.4% for women). This percentage increased to 38.5% for all adults when racial- or ethnic-specific criteria were used (41.9% for men; 35.0% for women). The prevalence increases with age, peaking in the 60- to 69-years group, which parallels a correlation with weight gain  with increasing age. Caucasian and Mexican-American men had a higher prevalence of metabolic syndrome than African American men, whereas the  prevalence for women was lower among Caucasian women than for African American or Mexican American women.10

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