Diabetes and C-Reactive Protein

Linking Diabetes and C-Reactive Protein

9/2/11 7:53 PM

DOC News

docnews.diabetesjournals.org DOC NEWS July 2004 vol. 1 no. 1 1-17

Linking Diabetes and C-Reactive Protein Wendy Meyeroff Inflammation marker may raise more questions than answers As the link between chronic inflammation and the development of cardiovascular disease, diabetes, and other conditions becomes clearer, more physicians are ordering tests for the inflammatory marker Creactive protein (CRP).

Although authorities recognize that CRP is a useful tool for assessing cardiovascular risk, some suggest that widespread adoption of the test may raise more questions than it answers—Which patients should be tested? What is the significance of the results? Once armed with CRP values, what action is the clinician expected to take? Which patients should be treated, and how?

Sorting through available data about the clinical relevance of CRP leads to incomplete and sometimes contradictory information.

In January 2003, a joint panel of experts from the American Heart Association (AHA) and the Centers for Disease Control and Prevention (CDC) released a statement acknowledging that testing for CRP is useful in determining a patient's risk for cardiovascular disease.

A growing body of scientific data links CRP with cardiovascular events. Studies indicate that patients with the highest levels of CRP have about twice the risk as those with the lowest levels.

Dana King and colleagues at the University of South Carolina report a close correlation between CRP levels and glycated hemoglobin (A1C), suggesting an association between glycemic control and systemic inflammation among patients with diabetes.

However, there is no evidence that close monitoring of CRP results in improved patient outcomes. “I don't think it's been proven that people who don't have elevated CRPs are not in danger,” said Neal Weintraub, MD, of the University of Iowa.

Richard Sadovsky, MD, of the State University of New York/Downstate Medical Center in Brooklyn, N.Y., suggests that CRP is most useful when treating a patient with early signs of diabetes or cardiovascular disease. “You're trying to decide in your mind just how aggressive you should be in treating this patient,” he said. An elevated result may indicate the need for stepping up the intensity of therapy.

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Linking Diabetes and C-Reactive Protein

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Experts disagree over whether clinicians should test patients who are already at high risk of cardiovascular events, such as those with diabetes. “You normally don't worry about testing for CRP because you know that patient is already at high risk for cardiovascular disease,” said Sadovsky. “They should already be getting maximal treatment no matter what their CRP level.”

Eric Topol, MD, chair of cardiovascular medicine at The Cleveland Clinic, feels that testing in such patients could be valuable because it “separates those for whom there's still some room to go in their medical or their lifestyle plan.”

On the other hand, experts say, an elevated CRP could be pointing to some other problem. Although CRP is a stable assay and offers certain advantages over other markers, the test is not infallible. CRP is “not a very specific test for vascular inflammation,” said Thomas A. Pearson, MD, co-chair of the AHA/CDC writing group.

A patient with an extremely high level of CRP—over 10 mg/L—observed after repeated testing and in the absence of other risk factors should be evaluated for other, noncardiovascular causes.

Elevated levels can indicate inflammation caused by bronchitis, immunologic disorders such as lupus and rheumatoid arthritis, or even gingivitis and periodontitis. It's conceivable that all a patient with an elevated CRP needs is improved dental hygiene.

“If my patient is 45, with no family history of heart disease, isn't obese, isn't smoking, then I'd start looking for other causes of inflammation,” said Sadovsky.

Fortunately, CRP levels respond to medication therapy, including treatment with statins, insulin, and the insulin-sensitizing glitazone drugs. Whether treatment reduces the risk of cardiovascular disease and impact on morbidity and mortality remains to be seen in clinical studies. !

Coming to Terms with CRP When speaking of CRP results, clinicians are likely referring to newer highsensitivity tests that are more precise and accurate than assays in years past.

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Linking Diabetes and C-Reactive Protein

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Older tests measured levels from 3 to 200 mg/L, whereas high-sensitivity CRP (hs-CRP) measures levels as low as 0.2 mg/L. Current recommendations call for an average of two assays, fasting or nonfasting, about 2 weeks apart.

Under current guidelines, a hs-CRP level below 1.0 mg/L is considered low risk, whereas 1.0 to 3.0 mg/L is average risk and 3.0 mg/L or greater is considered high risk.

Because CRP testing is not yet seen as a standard preventive measure in the way testing for cholesterol is, the assay is generally not covered by insurance plans.

Footnotes American Diabetes Association, Inc.

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