Emerging Concepts in Identification, Treatment, and Prevention of the Metabolic Syndrome

Editor's Note: Commentary based on Sperling LS, Mechanick JI, Neeland IJ, et al. The CardioMetabolic Health Alliance: working toward a new care model for the metabolic syndrome. J Am Coll Cardiol 2015;66:1050-67.

The term "metabolic syndrome" (MetS) is well known to health care providers and, in fact, to much of the lay public. However, despite the widespread familiarity with this concept, it seems that clinicians very rarely diagnose MetS or describe the importance of this syndrome to patients. It also appears that health care providers rarely change their management strategy based on the presence of MetS, even when it is clearly present.

In the United States, the most commonly used definition of MetS is from the National Cholesterol Education Program (NCEP), which defines the condition as the presence of at least three of the following: 1) glucose ≥ 100 mg/dl, 2) waist circumference at least 102 cm in men and at least 88 cm in women, 3) triglycerides ≥ 150 mg/dl, 4) high-density lipoprotein cholesterol (HDL-C) < 40 mg/dl in men or < 40 mg/dl in women, and 5) blood pressure at least 130/85 mm Hg or on antihypertensive medications.1 The pathogenesis of MetS has been described as a mosaic of genetic predisposition to insulin resistance and environmental factors, mainly increased abdominal adiposity. Due to increased genetic tendency to MetS, in certain racial and ethnic minorities, particularly South Asian Americans, some have suggested an even lower cut-off for waist circumference.

Certainly, a number of controversies regarding MetS remain debated. The cut offs for each metabolic parameter are certainly arbitrary. It is unclear whether the risk associated with MetS is equal to or greater than the risk of the sum of its individual characteristics. And, the exact relative contribution of genetic and environmental factors to the development of the MetS remains uncertain.

Yet, as was highlighted by a recent executive summary from the CardioMetabolic Health Alliance, a multidisciplinary "think tank" convened by the American College of Cardiology, MetS is a useful clinical construct that identifies a "complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, ... progressive in its course, ... associated with serious and extensive comorbidity, but ... clinically under-recognized."2 The data are certainly unwavering: MetS is common, present in approximately 25% of adults in the United States, and is associated with a significant increase in the risk of developing type 2 diabetes and premature cardiovascular events in addition to a number of non-cardiovascular adverse outcomes. Generally, the risk associated with MetS increases with the number of abnormal parameters present and the severity of those metabolic abnormalities.

Current guidelines suggest that when MetS is identified, the primary focus needs to be on lifestyle modification and potentially pharmacological treatment of the individual risk components, according to disease-specific guidelines. Clearly, there is ample evidence that intensive lifestyle modification can forestall the consequences of MetS. Notably, the National Institutes of Health sponsored the Diabetes Prevention Program (DPP) In the DPP, among subjects with "pre-diabetes," a lifestyle program that focused on an approximately 7% decrease in weight and 150 minutes of exercise per week led to a 58% reduction in the risk of developing diabetes as compared to usual care.3 Importantly, in the DPP, this intensive lifestyle modification also led to a 41% decreased risk of developing the MetS among those who did not meet criteria at baseline.

So, based on the above discussion, the MetS is well known, well understood, common, important for health, and treatable/preventable, yet its identification and management have not managed to make its way into common clinical practice despite over a decade of focused attention. This dissonance led the organizers of the CardioMetabolic Health Alliance to gather a think tank in June 2014 as a call to action focused on this unmet clinical need.2

In addition to affirming the prevalence, pathogenesis, and complications of the MetS, this conference identified a number of emerging concepts (EC) that are noteworthy:2

  • EC.1: MetS should be classified by subtype and stage, which translate to specific evidence-based management algorithms to improve clinical outcomes.
  • EC.2: Improved metrics to define high-risk obesity are needed and may be characterized by evidence-based assessments including, but not limited to, waist circumference, body composition, and imaging-based assessments of ectopic fat and/or visceral adipose tissue.
  • EC.3: Structured lifestyle interventions for residual risk reduction are required. Focused research and improved education on lifestyle medicine are also needed.
  • EC.4: Health care disparities need to be addressed with respect to: 1) access to structured lifestyle interventions; 2) integrated care delivery systems with enhanced provider awareness, accountability, and communication, along with tools to appropriately identify and treat those at risk; and 3) community engagement.
  • EC.5: New care models, such as the patient-centered medical home (PCMH) and Accountable Care Organizations (ACOs), are needed that incorporate new technology, electronic health records, and novel reimbursement paradigms.

Of these, I find that the most intriguing are the staging and subtyping of patients with MetS. The recognition that there are different phenotypes (and perhaps corresponding genotypes) of patients with MetS, including lipid dominant, vascular dominant, adiposity dominant, insulin resistance dominant, each with varying susceptibility to cardiometabolic and non-cardiometabolic consequences, is a major leap forward for further research in the field. Additionally, providing a staging system (A = at risk without any criteria, B = at risk with at least one criteria, C = presence of MetS without end-organ damage, and D = presence of MetS with end organ damage) highlights the concept of primordial prevention – lifestyle changes to prevent the development of cardiovascular risk factors in the first place and provides a very useful clinical construct.

The conference also determined that a new care model for patients with MetS "is essential and should include screening, risk stratification, and algorithmic management of patients according to the specific subtype and stage."2 By necessity, this management strategy would need to include structured interventions regarding diet, exercise and obesity management. While the executive summary spells out the importance of all stakeholders – including community health leaders, health care providers, and third-party payers – working together to adopt such an approach, the prescription is short on actionable details. This is no fault of the authors. Rather, it is a natural consequence of the deeply rooted system of incentives that have been built around health care reimbursement in the United States. In my opinion, unless or until we find a path that aligns the interests of major stakeholders and rewards adoption of successful integrated lifestyle and clinical management programs, it is unlikely that we will see major improvements in identification, prevention and management of MetS as a disease cluster. The current approach, in which health care providers treat each component of MetS as a distinct clinical entity rather than focusing on the management of underlying pathogenesis (i.e., obesity and insulin resistance) is the natural result of our current delivery system. Once again, in my opinion, if we want to change our results, we need to fundamentally change our view of how we approach the concept and business of managing health and disease in the United States.


  1. Grundy SM, Brewer HB Jr., Cleeman JI, et al., for the Conference Participants. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109:433-8.
  2. Sperling LS, Mechanick JI, Neeland IJ, et al. The Cardiometabolic Health Alliance: working toward a new model for the metabolic syndrome. J Am Coll Cardiol 2015:66;1050-68.
  3. Knowler WM, Barrett-Connor E, Fowler SE, et al.; on behalf of the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Eng J Med 2002;346:393-403.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Diet

Keywords: Adiposity, Algorithms, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Cholesterol, HDL, Comorbidity, Diabetes Mellitus, Type 2, Diet, Electronic Health Records, Genetic Predisposition to Disease, Glucose, Health Personnel, Healthcare Disparities, Insulin, Insulin Resistance, Insurance Pools, Insurance, Health, Reimbursement, Intra-Abdominal Fat, Life Style, Life Style, Lipoproteins, HDL, Metabolic Syndrome X, Obesity, Abdominal, Obesity, Patient-Centered Care, Phenotype, Prevalence, Primary Prevention, Risk Factors, Risk Reduction Behavior, Triglycerides, Waist Circumference

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