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Should we dump the metabolic syndrome? No

BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39484.636586.94 (Published 20 March 2008) Cite this as: BMJ 2008;336:641

Rapid Response:

Are we using the wrong targets and the wrong terminologies in assessing the usefulness of the Metabolic syndrome?

The 'popularity' which some may wish to equate with "clinical value" of the metabolic syndrome, is such that it has even been suggested that metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population (1). Whereas this may require much further investigation of the actual predictive value of the metabolic syndrome, it remains true that the clustering of risk factors grouped under the 'metabolic syndrome'mimics closely the clustered occurence of non-communicable diseases such as diabetes mellitus and cardiovascular disease (2), although I agree with M.Coceani that the metablic syndrome should not move from the status of 'predictor of relative risk' to the status of disease in its own right.

Until an explanation is found regarding why all those with the 'metabolic syndrome' do not develop the diseases for which it is a proposed 'risk factor' or "risk predictor", the 'cigarette smoking' history will repeat itself. TDR Hockaday is right in questioning the reference to obesity and a sedentary lifestyle as 'underlying causes'of the metabolic syndrome.

Obesity is itself the result of metabolic alterations which are brought about by aetiological factors, which remain largely unknown. Obesity therefore is itself part of a pathogenic mechanism triggered by 'underlying causes'. The question that may arise is therefore, is obesity a 'cause' or a 'risk factor' for diabetes mellitus and cardiovascular diseases, or is it part of a common pathogenic pathway for these conditions triggered by overlapping causes. In fact the other components of the metabolic syndrome are themselves better classified as pathogenic mechanisms/conditions rather than 'risk factors'. In any case, unless we can positively identify the pathogenic mechanism(s)that underlie the clustering of "risk factors" forming part of the metabolic syndrome, we remain unfortunately in a chicken and egg situation regarding whether, for instance,obesity or insulin resistance is the first to arise.

I do not follow the logic that is used to conclude that focusing on the cluster of cardiovascular disease and diabetes "risk factors" emphasises the 'multifactorial nature of the risk for these diseases'. Terminologies must be put in their right perspectives: it is clear that the components of the metabolic syndrome are the result of some aetiological cause(s) and of some pathogenic process(es) and that they are not in themselves aetiological agents and cannot thus be classified as 'risk factors', epidemiologically speaking. I would say that clustering of the components of the metabolic syndrome points more towards a "commonality of cause(s) and pathogenicity" for these diseases. This issue has also been addressed elsewhere (3), but there is no proof as yet of the syndrome being the result of a common underlying pathological process. It is however clear that the choice of the unifying pathogenic factor is important and that components such as insulin resistance and hyperinsulinaemia, not universally associated with other components of the metabolic syndrome, may themselves be the results of common upstream pathogenic mechanism(s).

I can appreciate that the concept of the metabolic syndrome has shed light on the commonality of pathogenic pathways leading to these two Type 2 diabetes and CVD , but how has the metabolic syndrome rendered the "management" of type 2 diabetes better? Type 2 diabetes, on its own, has clinical complications worthy of ensuring a proper clinical management of the disease with or without the looming risk or presence of cardiovascular disease.

I also do not agree that "the syndrome provides a simple public health strategy to define those at higher risk". In fact, I think that the authors are not doing justice to the 'metabolic syndrome' by attributing to it multiple and sometimes unjustified merits and refusing to admit its limitations. Addressing these limitations may serve it better in the long run.

The assessment of the risk predictive value of the metabolic syndrome should continue to be the a focus for research and, public health policies and community health promotion programmes should not just cast it aside prematurely. Research has so far focused on the risk predictive value of the syndrome in adults from different age, gender and ethnic groups. However, research focus should also depart from these classical target groups because if we truly want to define "those at higher risk", with a view, I assume of halting, as early as possible, the appearance of overt disease, then, targeting adults is already too late in the pathogenic process comprising disease development. We should thus target children and adolescents. Using current definitions, metabolic syndrome has been found to have a high prevalence amongst children in the US (4,5).More studies should focus on children and adolescents for whom however, the current definitions used to assess presence and prevalence of metabolic syndrome may not be appropriate, requiring thus more studies on paediatric definitions of the syndrome. This is especially so when treatment options for conditions like obesity in youth, includes pharmacotherapy and surgery (6).

The impact and usefulness of different definitions of the metabolic syndrome and of the thresholds of the components of the metabolic syndrome in primary healthcare and different target groups, known to vary (7), should be further researched to avoid unecessary alarm and to increase cost-effectiveness. Metabolic syndrome has been described as the result of the maladaptation to overnutrition of genes selected to survive undernutrition because of the limited nutrition on which mankind is assumed to have evolved(8). This situation of overnutrition affects the whole of society and not just those classified as "overeaters". On the evolutionary scale, the emergence of obesity within a couple of generations is classified as too rapid to be accounted for by a genetic change and is believed to be the result of a change in environment instead (8). So again the issue of appropriate targets for studies arises. Studies on any link between the metabolic syndrome and oestrogen levels/metabolism must not be forgotten, in view of the association of gender, polycystic ovary syndrome and fat distribution (central obesity) with the metabolic syndrome.

References:

1)Gogia A, Agarwal PK. Metabolic syndrome. Indian J Med Sci 2006;60:72-81.

2)Grundy SM. Metabolic syndrome : Connecting and reconciling cardiovascular and diabetes worlds. J.Am. Coll. Cardiol. 2006; 47: 1093- 1100.

3) Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome : Time for a critical appraisal. Diabetes care. 2005.28(9):2289-2304.

4) Kranz S, Mahood LJ and Wagstaff DA. Diagnostic criteria patterns of US children with metabolic syndrome: NHANES 1999-2002. Nutrition Journal. 2007; 6:38. doi:10.1186/1475-2891-6-38

5)Dhuper S et al. Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents : a cross-sectional study. Cardiovascular Diabetology.2007;6:4. doi:10.1186/1475-2840-6-4

6) Jolliffe CJ, Janssen I. Vascular risks and management of obesity in children and adolescents. vascular Health and Risk management. 2006; 2(2) :171-187.

7) Moebus S et al; Impact of 4 different definitions used for the assessment of teh prevalence of the metabolic syndrome in primary healthcare : the German Metabolic and cardiovascular Risk project (GEMCAS). Cardiovascular Diabetology. 2007; 6:22 doi: 10.1186/1475-2840-6- 22

8)Wilkin TJ, Voss LD. Metabolic Syndrome ; maladaptation to a modern world. J R Soc Med 2004;97 : 511-520.

my e-mail address : seetulg@uom.ac.mu

Competing interests: None declared

Competing interests: No competing interests

29 March 2008
Sharmila P Seetulsingh-Goorah
Associate Professor in Health Sciences
Department of Health Sciences,Faculty of Science, University of Mauritius, Reduit, Mauritius.