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Inflammation Marker Tied to Type 2 Diabetes by Carol Cruzan Morton The Harvard FOCUS, March 19, 2004 Every extra pound proportionately increases the risk of type 2 diabetes, even in the normal weight ranges. But not every overweight and obese person develops the disease. Now researchers at HSPH and HMS have found another strong and independent predictor of diabetes, C-reactive protein (CRP), a marker of inflammation that is better known as a risk factor for cardiovascular disease.
In a study published in the March issue of Diabetes, the highest levels of CRP in the blood quadrupled the chance of developing diabetes in women compared to the lowest levels, even after adjusting for body weight.
The findings support the idea that a low-grade inflammation underlies the pathogenesis of type 2 diabetes. The study also links two cytokines released by fat--recently dubbed "adipokines"--with increased risk of diabetes. Women with the highest levels of TNF-alpha receptor 2 had a 64 percent increased risk of diabetes, and women with the highest levels of interleukin-6 had a 91 percent increased risk compared to women with the lowest levels. The two adipokines have similar biological pathways and can increase levels of CRP, which is not produced by fat.
"Being able to predict a fourfold increased risk of type 2 diabetes may have major clinical implications in targeting interventions, because we're already talking about a common disease," said senior author JoAnn Manson, the Elizabeth F. Brigham professor of women's health at HMS and Brigham and Women's Hospital. "At this point, we're not saying that doctors should routinely measure CRP for the purpose of predicting type 2 diabetes. We would like to see more research, but it looks promising as a marker of risk."
Although the researchers adjusted the results to eliminate the risk of extra weight and lifestyle factors, it makes sense to Manson that substances produced by fat might play a role in the disease process.
"Fat tissue is often regarded as an inert storage depot," she said. "In reality, it is a highly active and dynamic organ that secretes hormones and cytokines. The mechanisms through which fat tissue causes insulin resistance in distant tissue, such as liver and skeletal muscle, is not well understood. This study really suggests that some circulating messenger produced by the fat cell induces insulin resistance and increases the risk of developing type 2 diabetes, and this may relate to increased risk of cardiovascular disease as well."
Led by first author Frank Hu, HSPH associate professor of nutrition and epidemiology and HMS assistant professor of medicine at BWH, the researchers compared 737 women in the Nurses' Health Study who developed diabetes within 10 years of providing blood samples with 785 women in the study of similar age, race, and weight who did not develop diabetes.
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