Definitions of the Insulin Resistance Syndrome

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Abstract
Richard Pasternak (Boston, MA) discussed the deliberations that led the National Cholesterol Education Program Adult Treatment Panel (ATP) III to propose a new definition of the metabolic syndrome (1) and the impact of this proposal in heightening awareness of the insulin resistance syndrome (IRS). Coronary heart disease (CHD) is the main cause of death in the developed world, and Pasternak noted that contrary to general perceptions, malignancy is only approximately half as frequent a cause of mortality as CHD among women. The concept of metabolic syndrome extends in a precise way an important subset of patients at high risk for CHD. The definition was created to be clinically practical, evidence based, and applicable to existing datasets. The ATP did not find adequate evidence to recommend routine measurement of insulin sensitivity or of inflammatory markers. The 2-h glucose was not included because it was similarly felt not to add sufficient numbers of persons to justify the additional effort involved. The panel has been criticized for not calling the metabolic syndrome a CHD equivalent, but Pasternak pointed out that at that time there was no evidence that this was the case. Rather, the presence of the metabolic syndrome was felt to accentuate the risk accompanying elevated LDL cholesterol, mediated through existing and emerging risk factors. Clinical trials show evidence for modification of atherogenic dyslipidemia, blood pressure, and the prothrombotic state (with aspirin, which the panel recommended only for persons with CHD but which Pasternak suggested is appropriate for all persons with the syndrome) in persons undergoing LDL-lowering therapy. The primary management strategy should be to reverse its root causes of obesity and physical inactivity, with an option to intensify LDL lowering. It is notable that metabolic syndrome is particularly likely to be present in younger persons with CHD (2). With modification of the definition, metabolic syndrome is present in ∼10% of children. Pasternak stated that analysis of the Atherosclerosis Risk in Communities study shows that 52% of persons with but 23% of those without metabolic syndrome have increased carotid intima-media thickness (IMT). Analysis of the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) trial suggests that the metabolic syndrome identifies a group among those with existing CHD that has greater absolute benefit from lipid-lowering treatment. Pasternak concluded by noting the association of C-reactive protein with atherosclerotic risk in the West of Scotland Coronary Prevention study, with additive effect to the presence of metabolic syndrome (3). In answer to a subsequent question, he also noted the usefulness of measurement of the ankle-brachial systolic pressure ratio to ascertain whether a person has cardiovascular disease (CVD).