BMJ  2008;336:640 (22 March), doi:10.1136/bmj.39477.500197.AD

Head to Head

Should we dump the metabolic syndrome?: Yes

Edwin A M Gale, professor of diabetes

1 Diabetes and Metabolism, University of Bristol, Medical School Unit, Southmead Hospital, Bristol BS10 5NB

Edwin.Gale{at}bristol.ac.uk

doi: 10.1136/bmj.39484.636586.94

The number of people with the metabolic syndrome is rising alongside obesity. Nevertheless, Edwin Gale believes the diagnosis has little practical value. George Alberti and P Z Zimmet, however, think it increases the detection of people at high risk of diabetes and heart disease

Type 2 diabetes and lesser degrees of glucose intolerance are associated with insulin resistance, central obesity, hypertension, and dyslipidaemia. The term metabolic syndrome describes the same constellation, with or without glucose intolerance. Although these associations are well established, their pathophysiological basis remains unclear, and no unifying feature has emerged. Attempts have been made to assemble the various features of the metabolic syndrome into a single all-purpose definition, for which diagnostic, prognostic, and therapeutic value has been claimed. Diagnosis of the metabolic syndrome is redundant in those who already have diabetes and adds nothing to the management of those who do not.

Unclear definition

A cluster of clinical features constitutes a syndrome, but attempts to define the metabolic syndrome as a clinical entity have been hampered by the lack of an agreed unifying feature. The grouping was first described in patients with type 2 diabetes,1 and the wider concept of a "metabolic" syndrome arose when Gerald Reaven suggested that the common factor was insulin resistance rather than diabetes.2 Insulin resistance is, however, unsatisfactory as a core feature, for it cannot be defined or measured easily and is inconsistently related to the individual features of the syndrome.3

Expert panels have made various attempts to establish a working definition using different scoring systems.4 5 The endeavour was complicated by uncertainty about which associated features to include, what thresholds to set, and what exactly the experts were trying to achieve. The schemes that emerged have proved useful for statistical analysis and epidemiological comparison, but not for clinicians, who hardly ever record the diagnosis.6

The most recent definition, proposed by an expert committee of the International Diabetes Federation, bases the syndrome around a new core feature, central obesity, and is intended for clinical use (box).4 Representatives of the American Diabetes Association and the European Association for the Study of Diabetes have, however, argued that any such attempt is premature.5 This is not a turf war: the confrontation reflects genuine perplexity within the diabetes community. One party maintains that a working definition is needed to resolve existing confusion; the other party argues that an inadequate definition merely adds to it.


International Diabetes Federation definition of metabolic syndrome4
Presence of central obesity—Waist circumference varies with ethnicity (see bmj.com). If body mass index is >30 central obesity can be assumed

Plus any two of the following:

  • Triglyceride concentration ≥1.7 mmol/l or specific treatment for this lipid abnormality
  • High density lipoprotein cholesterol <1.03 mmol/l in men, <1.29 mmol/l in women, or specific treatment for hypercholesterolaemia
  • Systolic blood pressure ≥130 mm Hg or diastolic ≥ 85 mmol/l, or treatment for hypertension
  • Fasting plasma glucose ≥5.6 mmol/l or previously diagnosed glucose type 2 diabetes. If ≥5.6 mmol/l, oral glucose tolerance test is strongly recommended but is not necessary to diagnose the syndrome


The proposed definition of the metabolic syndrome embraces overt diabetes and people with established cardiovascular disease, yet also purports to predict these as outcomes.2 The "now you see it, now you don’t" approach to diabetes means that it can be included when estimating the apparent health consequences of the syndrome in population studies, yet becomes an end point in predictive analyses. From a more practical point of view, energetic screening and treatment for obesity, hypertension, and dyslipidaemia already form the basis of managing diabetes. Diagnosis of the metabolic syndrome adds nothing to the understanding or clinical management of people with known diabetes and is therefore redundant. Future consideration of the syndrome should exclude diabetes and known cardiovascular disease.5

Clinical value

The quest for a worldwide index of the health implications of central obesity is praiseworthy but problematic, given the limitations of waist circumference as a surrogate.3 Clinical measures do not need to be perfect, but they do need to be consistent, and the relation between girth and fat distribution varies from one population to another. Different waist measures are needed for different ethnic groups, and race-for which no satisfactory definition exists-thus enters the equation (tableGo).4 Use of a sliding scale for waist circumference has the further consequence that an independent yardstick-cardiovascular risk-is then needed to calibrate one population with the next. The result is a circular definition, for vascular risk defines the syndrome and the syndrome defines vascular risk.


View this table:
[in this window]
[in a new window]

  		International Diabetes Federation definitions for central obesity

 
Diagnosis of the metabolic syndrome enhances prediction of diabetes and cardiovascular disease, if these are not already present, but impaired glucose tolerance alone is better than the combined features of the syndrome in predicting diabetes,3 4 5 and it is unsurprising that combining known cardiovascular risk factors enhances cardiovascular risk. The metabolic syndrome is consistently outperformed by scoring systems that incorporate age, sex, and smoking together with personal and family history of heart disease. These have the further advantage of treating continuous variables as continuous, whereas the metabolic syndrome treats them as dichotomous.3 4 5

In sum, the metabolic syndrome is a handy clinical label that lacks a useful definition. The latest attempt is characterised by an elastic measure of the proposed unifying feature-central obesity-and has no agreed pathophysiological basis. A flourishing academic industry has been founded on a diagnostic artefact with little prognostic or therapeutic value. Reaven himself bids farewell to his syndrome, in so far as clinical value is concerned, with the words requiescat in pace (rest in peace).3 To which we may add, Amen.

doi: 10.1136/bmj.39484.636586.94

Competing interests: None declared.

References

  1. Gale EAM. The myth of the metabolic syndrome. Diabetologia 2005;48:1679-83.[CrossRef][Web of Science][Medline]
  2. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607.[Abstract]
  3. Reaven GM. The metabolic syndrome: requiescat in pace. Clin Chem 2005;51:931-40.[Abstract/Free Full Text]
  4. Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabetic Med 2006;23:469-80.[CrossRef][Medline]
  5. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Society for the Study of Diabetes. Diabetologia 2005;48:1684-99.[CrossRef][Web of Science][Medline]
  6. Ford EF. Rarer than a blue moon. The use of a diagnostic code for the metabolic syndrome in the US. Diabetes Care 2005;28:1808-9.[Free Full Text]

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati    What's this?

Relevant Articles

The confidence to doubt
Fiona Godlee
BMJ 2008 336: 0. [Extract] [Full Text]

Should we dump the metabolic syndrome? No
K G M M Alberti and P Z Zimmet
BMJ 2008 336: 641. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

  • Ley, S. H., Harris, S. B., Mamakeesick, M., Noon, T., Fiddler, E., Gittelsohn, J., Wolever, T. M.S., Connelly, P. W., Hegele, R. A., Zinman, B., Hanley, A. J.G. (2009). Metabolic syndrome and its components as predictors of incident type 2 diabetes mellitus in an Aboriginal community. CMAJ 180: 617-624 [Abstract] [Full text]  
  • Worm, S. W., Sabin, C. A., Reiss, P., El-Sadr, W., d'Arminio Monforte, A., Pradier, C., Thiebaut, R., Law, M., Rickenbach, M., De Wit, S., Lundgren, J. D., Friis-Moller, N. (2009). Presence of the Metabolic Syndrome Is Not a Better Predictor of Cardiovascular Disease Than the Sum of Its Components in HIV-Infected Individuals: Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study. Diabetes Care 32: 474-480 [Abstract] [Full text]  
  • Sheikh, K. (2008). Metabolic Syndrome and Stroke. Stroke 39: e163-e163 [Full text]  

Rapid Responses:

Read all Rapid Responses

Metabolic Syndrome may not be dumped
M E Nassar, M.D., Ph.D.
bmj.com, 22 Mar 2008 [Full text]
Metabolic syndrome and smoking
Hiroshi Kawane, et al.
bmj.com, 24 Mar 2008 [Full text]
The metabolic syndrome and the Broad Street pump
Sern Lim
bmj.com, 25 Mar 2008 [Full text]
Should we dump Metabolic Syndrome: Yes
Anukul GARG
bmj.com, 25 Mar 2008 [Full text]
Aetiology and use of metabolic syndrome
John A. Lee
bmj.com, 25 Mar 2008 [Full text]
The metabolic syndrome – revise the processes of care, don’t dump the concept
Tim A Holt
bmj.com, 26 Mar 2008 [Full text]
Practical use of the metabolic syndrome in primary care.
Clive L Morrison
bmj.com, 26 Mar 2008 [Full text]
The metabolic syndrome - a longitudinal perspective
Bernard M Y Cheung
bmj.com, 26 Mar 2008 [Full text]
Do not dump but LEARN to recognize the metabolic syndrome.
Laszlo Bense
bmj.com, 26 Mar 2008 [Full text]
Focus on causality.
José Pedro L. Nunes
bmj.com, 28 Mar 2008 [Full text]
Should the Metabolic Syndrome be replaced by "The blood hyperviscosity syndrome " ?
Les O. Simpson
bmj.com, 29 Mar 2008 [Full text]
Don’t Dump the Metabolic Syndrome – It’s Important in Children and Adolescents!
Carroll Sean, et al.
bmj.com, 10 Apr 2008 [Full text]
Cardiovascular risk stratification
Irugal D M Disssanayake
bmj.com, 25 Apr 2008 [Full text]
Rather than dumping the concept it will be useful to separate diseases from symptoms
Arya K Kumarasena
bmj.com, 16 May 2008 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ