The Metabolic Syndrome: Inflammation, Diabetes Mellitus, and Cardiovascular Disease

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There is accumulating evidence that inflammation is an important risk factor in cardiovascular disease (CVD). Elevated levels of the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk for CVD and diabetes mellitus. Adding hs-CRP to the definition of the metabolic syndrome has been shown to improve the prediction of CVD. Elevated hs-CRP levels may also be predictive of development of the metabolic syndrome. Current definitions of the metabolic syndrome differ, and cardiovascular risk appears to differ according to which component risk factors are present. Further studies are required to identify a widely accepted criterion for the syndrome that will optimally predict the risk of diabetes and CVD. It is possible that such a definition will include a measure of inflammation.

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C-Reactive Protein and the Metabolic Syndrome in Predicting Coronary Artery Disease and Diabetes

The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) clinical criteria for the metabolic syndrome are shown in Table 1.3 The diagnosis of metabolic syndrome is based on the presence of any 3 of the criteria listed. Several problems have been noted with this definition of the syndrome. First, it can be met without the presence of insulin resistance, which is a central component of the World Health Organization (WHO) definition of the syndrome.4 Second, waist

C-Reactive Protein Levels and Risk of the Metabolic Syndrome

There are data indicating that elevated hs-CRP levels predict development of the metabolic syndrome, at least in women. In 729 women during 6 years of follow-up in the Mexico City Diabetes Study, baseline hs-CRP was significantly correlated with development of the metabolic syndrome, which was defined as including ≥3 of the following: dyslipidemia (elevated triglycerides or low HDL cholesterol), hypertension, or diabetes. In 515 men studied, however, there was no significant correlation.7

C-Reactive Protein, Diabetes, and the Metabolic Syndrome

The Insulin Resistance Atherosclerosis Study (IRAS) found a linear increase in mean log hs-CRP values according to the number of metabolic disorders present in each of 1,008 patients without diabetes or CAD.8 The metabolic disorders consisted of dyslipidemia (elevated triglycerides and/or low HDL cholesterol), upper body adiposity, insulin resistance (measured by frequently sampled intravenous glucose tolerance tests), and hypertension. A prospective study in 1,047 subjects without diabetes in

Effects of Therapy on C-Reactive Protein Levels

Although it is still unclear whether hs-CRP should be a treatment target, it is of interest to determine what types of therapeutic interventions produce changes in hs-CRP levels. Several recent studies indicate that statin treatment in patients with CAD produces significant reductions in hs-CRP—reductions that appear to be greater with regimens producing greater low-density lipoprotein cholesterol reductions.12, 13, 14

In a study of 509 patients with diabetes and triglyceride levels ≤6 mmol/L

Conceptual Framework for the Metabolic Syndrome

The management approach in patients with the metabolic syndrome depends on the syndrome’s perceived causes and the degree of risk attributed to its presence. Current general conceptual frameworks include (1) viewing the metabolic syndrome epidemic as being attributable to environmental causes (eg, the basic approach of NCEP ATP III), (2) viewing the syndrome as primarily the result of insulin resistance (eg, the WHO approach), and (3) viewing inflammation as the underlying cause of the

Conclusion

Ongoing investigation is required to determine how best to define the metabolic syndrome. Although it is clear that the presence of the syndrome is associated with increased cardiovascular risk, the levels of associated risk have not been clearly defined. Different proposed definitions would appear to result in different predictions of risk, and risk appears to differ according to which components of the proposed definitions are present. Inclusion of hs-CRP in the definition improves its

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