The Metabolic Syndrome: Time for a Critical Appraisal

Abstract

The term "metabolic syndrome" refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance. Since the term is widely used in research and clinical practice, we undertook an extensive review of the literature in relation to the syndrome's definition, underlying pathogenesis, and association with CVD and to the goals and impact of treatment. While there is no question that certain CVD risk factors are prone to cluster, we found 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." Diabetes Care 28:2289 -2304, 2005F or most of the 20th century, cardiovascular disease (CVD) was identified as the major cause of morbidity and mortality in the developed world. During this period there was considerable effort to understand the underlying biology of the disease and to identify the contributing risk factors. As risk factors were identified, it became apparent that more than one were often present in the same individual. Toward the end of the century, the clustering of CVD risk factors was first described, most notably the simultaneous presence of obesity, type 2 diabetes, hyperlipidemia, and hypertension (1-3). Although insulin resistance (i.e., resistance to insulin-stimulated glucose uptake) as a feature of type 2 diabetes was first described many years earlier (4), hyperinsulinemia was also found to be a key feature of type 2 diabetes (5,6), as well as hyperlipidemia (7-9), obesity (10 -13), and hypertension (12)(13)(14). In addition, a cluster of heart disease risk factors seemed clearly related to type 2 diabetes (15).This risk factor clustering, and its association with insulin resistance, led investigators to propose the existence of a unique pathophysiological condition, called the "metabolic" (1-3) or "insulin resistance" (11) syndrome. This concept was unified and extended with the landmark publication of Reaven's 1988 Banting Medal award lecture (16). Reaven postulated that insulin resistance and its compensatory hyperinsulinemia predisposed patients to hypertension, hyperlipidemia, and diabetes and thus was the underlying cause of much CVD. Although obesity was not included in Reaven's primary list of disorders caused by insulin resistance, he acknowledged that it, too, was correlated with insulin resistance or hyperinsulinemia, and that the obvious "treatment" for what he termed "syndrome X" was weight maintenance (or weight loss) and physical activity.Reaven's seminal paper was followed by many studies documenting the clustering of CVD risk factors and their relatio...

Assessing Baseline and Temporal Changes in Cardiometabolic Risk Using Metabolic Syndrome Severity and Common Risk Scores

“…This appears to contribute to disease development in that prior studies indicated that MetS severity confers additional disease risk, even in models that include the individual risk factors,19, 22 contrasting with past perceptions that MetS “was not worth more than the sum of its parts.”35 Also, although MetS severity increases with age, age itself is not a component of the score, as it is with the ASCVD and FRS scores, and the models we tested were not adjusted for age, highlighting the importance of MetS severity for disease risk irrespective of age.…”

The Metabolic Syndrome and Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study

“…The prognostic utility of the metabolic syndrome construct has previously been called into question 24. Initial studies adjusting for traditional cardiovascular risk factors suggested that the metabolic syndrome construct carries prognostic weight 7, 25, 26.…”

Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

“…The intricacies of the debate among official agencies on the clinical importance of MetS [9] are beyond the scope of this article. As a first order approximation, however, we are inclined to follow Reaven's strategy in the Point/Counterpoint paper [10,89] for assessing the need for the concept of MetS.…”

“…A subset of these metabolic markers, the TAG:HDL ratio, has been proposed as a simple marker for identifying insulin resistance [8]. It has recently been questioned whether the risk attributed to MetS is greater than the sum of the individual symptoms [9] and, ironically, Reaven has taken the "Con" side on a debate on the viability and diagnostic usefulness of the concept [10,11]. Nonetheless, there seems little controversy on the inherent potential for risk in the individual components.…”