Liu Simin, Tinker Lesley, Song Yiqing, Rifai Nader, Bonds Denise E, Cook Nancy R, Heiss Gerardo, Howard Barbara V, Hotamisligil Gokhan S, Hu Frank B, Kuller Lewis H, Manson JoAnn E
Department of Epidemiology, University of California, Los Angeles, CA 90095-1772, USA.
Arch Intern Med. 2007;167(15):1676-85. doi: 10.1001/archinte.167.15.1676.
Inflammatory cytokines, including tumor necrosis factor alpha, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations.
Among 82,069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor alpha receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease.
After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor alpha receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. 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.
These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.
炎性细胞因子，包括肿瘤坏死因子α、白细胞介素6（IL-6）和高敏C反应蛋白（hsCRP），均与胰岛素抵抗及2型糖尿病相关。然而，全面评估它们在2型糖尿病发生中作用的前瞻性研究较少，尤其是在少数族裔人群中。
在参加女性健康倡议观察性研究的82069名年龄在50至79岁、无心血管疾病或糖尿病的绝经后女性中，我们前瞻性地研究了血浆肿瘤坏死因子α受体2、IL-6和hsCRP水平与糖尿病风险的关系。在中位随访期5.9年期间，将1584例临床糖尿病女性按年龄、种族、临床中心、采血时间和随访时间与2198例无该疾病的研究参与者进行匹配。
在对匹配因素和已知糖尿病风险因素进行调整后，所有3种标志物均与糖尿病风险增加显著相关；肿瘤坏死因子α受体2最高四分位数与最低四分位数相比的估计相对风险为1.47（95%置信区间[CI]，1.10 - 1.97），IL-6为3.08（95%CI，2.25 - 4.23），hsCRP为3.46（95%CI，2.50 - 4.80）（所有生物标志物的趋势P值均<0.01）。相互调整后，IL-6和hsCRP在每个种族组中仍具有显著性。虽然在种族与这些生物标志物对糖尿病风险的影响之间未观察到统计学上显著的相互作用，但在所有种族组中，hsCRP和IL-6与糖尿病风险增加的关联均呈现一致趋势。
这些前瞻性数据表明，IL-6和hsCRP水平升高与绝经后女性临床糖尿病风险增加持续且显著相关。
