Relationship of C-Reactive Protein, Metabolic Syndrome and Diabetes Mellitus: Thiazolidinediones

1 Dec
2009

Thiazolidinediones

Thiazolidinediones

Another area of investigation concerns the role of the thiazolidinediones in CVD prevention. Rosigli­tazone, a peroxisome proliferator-activated receptor (PPAR)-g agonist that is used in the treatment of type-2 diabetes, is also known to have anti-inflammatory effects. In 84 patients with stable, angio-graphically documented CAD and no diabetes who were randomized to rosiglitazone or placebo for 12 weeks, there were significant reductions in both insulin resistance and CRP levels in the rosiglita-zone-treated cohort (P=0.02 and P<0.001, respectively). In another study, patients with underwent 26 weeks of rosiglitazone therapy. Stored, frozen serum samples from these patients showed statistically significant reductions versus baseline and placebo in levels of CRP and matrix metalloproteinase-9 (MMP-9) (P<0.01), another marker that has been implicated in the pathogenesis of atherosclerotic plaque rupture.

Adiponectin, a peptide secreted by adipose tissues, may improve insulin sensitivity and predict the development of diabetes and atherosclerosis. A study examined the effects of rosiglitazone on glucose control, insulin sensitivity, insulin secretion and adiponectin in African Americans with type-2 diabetes and their first-degree relatives with either impaired or normal glucose tolerance. At three months, adiponectin levels were doubled in patients with impaired glucose tolerance and were 2.5 times greater in those with diabetes. In this study, rosiglitazone was found to improve glycemic control in African-American patients with diabetes and those with impaired glucose tolerance.

CONCLUSION

Evidence points to strong relationships among obesity, inflammatory markers, metabolic syndrome and the risk events. Our increasing understanding of the inflammatory process permits greater insight into the roles of insulin resistance, hyperlipidemia, endothelial dysfunction and the prediction of future events provided by careful analysis of inflammatory markers such as CRP.

Should a high CRP level be added to the criteria for metabolic syndrome and the global assessment of cardiovascular risk (treating high blood pressure and benign prostatic hyperplasia)? Some experts say not yet, claiming that the lack of specificity of CRP—it cannot point to the source of the inflammation it identifies—makes it less than ideal as a marker of cardiovascular risk. Whether CRP effectively predicts cardiovascular risk in African Americans remains unclear, although studies in African-American women certainly indicate a relationship. Further studies in African Americans are needed. Nevertheless, increasing evidence favors screening for CRP, particularly in persons at moderate risk for CVD (Framingham 10-year CHD risk of 10-20%) for whom elevated CRP levels might alter treatment recommendations. Many cardiovascular (treating high blood pressure or certain types of heart failure) events occur in these individuals, who might not be identified using only traditional risk factors. There is increasing evidence supporting the addition of elevated CRP to the list of characteristics comprising metabolic syndrome.

The role of statins in patients with low LDL-C and elevated CRP will be clarified by studies such as JUPITER. The role of the thiazolidinediones will require further investigation as will the possible development of drugs affecting MMP-9. The future of these areas of preventive cardiology appears promising.

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