Women with diabetes have higher levels of three inflammatory cytokines.


Elevated levels of inflammatory cytokines in the blood can predict type 2 diabetes in menopausal women years before the disease manifests itself, according to a large study.

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Researchers used data from the Women’s Health Initiative Observational Study, an ongoing long-term study at 40 centers across the country. It involves 82,000 postmenopausal women aged 50-75 years and included whites, blacks, Hispanics, and Asians.


Simin Liu, MD, ScD, professor of epidemiology and medicine at the University of California, Los Angeles School of Public Health and David Geffen School of Medicine, and colleagues examined baseline plasma levels of three cytokines: tumor necrosis factor-alpha receptor 2 (TNF-α-R2), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP).


During the six-year study period, diabetes developed in 1,584 women. These participants were then matched by age, ethnicity, and other criteria with a control group of 2,198 women.


Women with diabetes had significantly higher median levels of the three inflammatory cytokines at baseline compared with controls: 2,633 vs. 2,361 pg/mL for TNF-α-R2; 2.59 vs. 1.54 pg/mL for IL-6; and 4.0 vs. 2.1 mL for hs-CRP. The pattern persisted across the four ethnic groups, though the amounts varied. All three markers were also associated with increased diabetes risk.


Patients in the highest quartile of TNF-α-R2 were at 47% greater risk than those in the lowest quartile, according to a report in Archives of Internal Medicine (2007;167:1676-1685). Those in the highest quartiles of IL-6 and hs-CRP were at 3.0 and 3.46 times greater risk, respectively, than subjects in the lowest quartiles.


Comparing highest to lowest quartiles, relative risks were: 47% greater for TNF-α-R2, three times greater for IL-6, and and more than three times greater for hs-CRP. However, hs-CRP was the most consistent risk predictor across racial lines.


Women who developed diabetes had a greater proportion of traditional risk factors at baseline: family history, higher BMI, higher waist circumference, higher waist-hip ratio, and less physical activity.


Cytokine biomarkers provide another predictive tool. Identifying these markers by a simple blood test well before the disease begins will give clinicians added urgency when recommending the diet and exercise changes that can prevent disease, they noted.