Tumor necrosis factor-alpha, IL-6, and high-sensitivity C-reactive protein show potential as biomarkers.

Researchers at the University of California Los Angelese (UCLA) report that a large prospective study has reaffirmed the role of three inflammatory cytokines as a cause of type 2 diabetes. They believe that tumor necrosis factor-alpha, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) can be used as biological markers.


“This is a final confirmation of earlier studies about the underlying biology behind type 2 diabetes,” says Simin Liu, M.D., professor of epidemiology and medicine at UCLA. Previous research, however, was either done in very small groups or in animals, according to Dr. Liu. “Our study identified 1,600 new cases of diabetes and measured the blood markers before they developed the disease.”


The researchers took advantage of the Women’s Health Initiative Observational Study, an ongoing long-term evaluation of the association between behavior, socioeconomic status, diet, and other factors and the effect on a woman’s health. The scientists took baseline level measurements of inflammatory cytokines in women without any signs of diabetes who were between the ages of 50 and 79 and then tracked their health.


At the follow-up after 5.9 years, Dr. Liu’s team compared 1,584 women who had developed type 2 diabetes with 2,198  women who remained free of the disease matched by age, ethnicity, and other factors.


While all three cytokines were found to be related to an increased risk of clinical diabetes, hs-CRP appeared to be a more consistent predictor of increased risk in all four ethnic groups studied. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups, the researchers point out.


These associations were independent of traditional risk factors such as obesity or elevated levels of glucose and insulin, the investigators assert.


The team reports that the estimated relative risks comparing the highest with the lowest quartiles for tumor necrosis factor  receptor 2 was 1.47, for IL-6 was 3.08, and for hsCRP was 3.46.


The study is published in the August 15 issue of Archives of Internal Medicine.

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