Commentary

Arteriosclerosis, Thrombosis, and Vascular Biology

Dr Dunbar and Dr Szapary have done an excellent job summarizing current data on metabolic syndrome (MetSyn), including the results from several recent reports of the National Institutes of Health and American Heart Association conferences on MetSyn recently reported in .¹ There remain considerable controversies about MetSyn in terms of its definition, the degree of risk for cardiovascular disease (CVD), and possible treatments. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III definition of MetSyn has gained popularity, partly because it is relatively simple and does not require measurement of glucose tolerance, fasting insulin, or urinary microalbuminuria, as does the World Health Organization (WHO) definition. Nevertheless, it is likely that a number of modifications may be made to the NCEP definition, including lowering waist circumference cut points in Asian populations, as well as lowering fasting glucose levels to 100 mg/dL rather than 110 mg/dL, as the American Diabetes Association has recently done.²

The risk of CVD in patients with MetSyn has remained controversial. Earlier papers from northern Europe by Isomaa et al3 and Lakka et al4 suggested that the relative risk for CVD in those with MetSyn may be 3 to 3.5 times higher than those without MetSyn. If these results are correct, one might treat individuals with MetSyn even without type 2 diabetes as if they had coronary heart disease (CHD) or CHD risk equivalent. For instance, this might mean a low-density lipoprotein goal of <100 mg/dL, or even lower according to the newly updated NCEP recommendations.⁵ In contrast, data from Alexander et al based on the National Health and Nutrition Examination Survey III data show an increased prevalence of CHD of 50% to 60%, suggesting that although patients with MetSyn might need some intensification of therapy, it is not necessarily automatically a CHD risk equivalent.⁶ The increase in risk reported by Alexander et al was more similar to that associated with a traditional NCEP major risk factors, such as hypertension or cigarette smoking.

A last major issue is should insulin-sensitizing therapies, such as thiazolidinediones (TZDs) and metformin, be prescribed for patients with MetSyn but not diabetes? Because of the absence of clinical trials involving hard or even soft end points in subjects with MetSyn, it is premature to prescribe insulin-sensitizing agents for patients with MetSyn if they do not have diabetes. However, a physician who believes such therapy might be helpful may want to consider performing a glucose tolerance test.

Among patients without diabetes but with MetSyn (based on fasting glucose levels alone), perhaps 20% to 30% of subjects will have a 2-hour glucose level exceeding 200 mg/dL and thus be classified as having diabetes. In such a case, the use of insulin-sensitizing agents is, of course, permissible. In subjects with normal glucose tolerance tests, use of insulin-sensitizing agents should be avoided. In subjects with impaired glucose tolerance, several clinical trials have shown that lifestyle changes and use of metformin, acarbose, and TZDs (specifically troglitazone) can prevent or delay the onset of type 2 diabetes. Here the health care provider can at least point to clinical trials, even though such interventions are not part of current guidelines or in the labeling for any medicine.

Arterioscler Thromb Vasc Biol.

1. Grundy SM, Brewer HB Jr, Cleeman JI, et al. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. 2004;24:e13-e18.

Diabetes Care.

2. Genuth S, Alberti KG, Bennett P, et al. Follow-up report on the diagnosis of diabetes mellitus. 2003;26:3160-3167.

Diabetes Care.

3. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. 2001;24:683-689.

JAMA.

4. Lakka HM, Laaksonon DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. 2002;288:2709-2716.

Circulation.

5. Grundy SM, Cleeman C, Bairey-Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. 2004;110:227-239.

Diabetes.

6. Alexander CM, Landsman PB, Teutsch SM, et al. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. 2003;52:1210-1214.