Circulating IL-18 and the risk of type 2 diabetes in women.
Circulating IL-18 and the risk of type 2 diabetes in women.
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DOI：
10.1007/s00125-009-1455-z
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发表时间：
2009-10
期刊：
影响因子：
8.2
通讯作者：
Hu, F. B.
中科院分区：
文献类型：
--
作者：
Hivert, M. F.;Sun, Q.;Shrader, P.;Mantzoros, C. S.;Meigs, J. B.;Hu, F. B.
关键词：
2型糖尿病的病理生理涉及促炎途径。我们检验了IL-18预测未来糖尿病病例的假设。我们采用了基于护士健康研究的嵌套病例对照设计。基线血液样本是在1989年至1990年间收集的。评估体重、生活方式（体育活动、饮食、吸烟）和糖尿病诊断的问卷每两年发放一次并进行评估（随访至2002年）。病例（n=1012）被定义为在抽血后至少1年发生2型糖尿病的女性。对照妇女（n=1081）按年龄、抽血日期、禁食状态和种族与病例相匹配。我们以第一个五分位数为参照，使用条件logistic回归计算IL-18五分位数中2型糖尿病的RR (95% CI)；调整包括匹配因素、糖尿病危险因素、BMI、脂肪因子水平（脂联素、抵抗素）和炎症蛋白（c反应蛋白、TNFr2和IL-6）。更高的IL-18水平与患糖尿病的风险增加相关，即使在匹配因素和多种糖尿病危险因素调整后也是如此：相对于第一五分位数，IL-18水平最高的五分位数患糖尿病的RR为1.75(1.41-2.18)（趋势p<0.0001）。在调整BMI （RR 1.44[1.15-1.80]，趋势p<0.0001）和脂联素水平（RR 1.28[1.02-1.60]，趋势p=0.006）后，仍观察到显著的关联趋势。进一步调整亚样本中的炎症标志物并没有显著改变结果。IL-18水平升高与糖尿病风险升高有关。这种关联独立于通常的危险因素，包括BMI和脂肪因子水平。
The pathophysiology of type 2 diabetes involves pro-inflammatory pathways. We tested the hypothesis that IL-18 predicts future diabetes cases. We used a nested case–control design based in the Nurses' Health Study. Baseline blood samples were collected between 1989 and 1990. Questionnaires to assess body weight, lifestyle (physical activity, diet, smoking) and diabetes diagnosis were sent out and assessed biennially (follow-up until 2002). Cases (n=1012) were defined as women developing type 2 diabetes at least 1 year after blood sampling. Control women (n=1081) were matched to cases by age, date of blood draw, fasting status and race. We calculated the RR (95% CI) of type 2 diabetes in quintiles of IL-18 using conditional logistic regression with the first quintile as referent; adjustments included matching factors, diabetes risk factors, BMI, adipokine levels (adiponectin, resistin) and inflammatory proteins (C-reactive protein, TNFr2 and IL-6). Higher IL-18 levels were associated with increased risk of developing diabetes, even after adjustment for matching factors and multiple diabetes risk factors: being in the highest quintile of IL-18 was associated with a RR of 1.75 (1.41-2.18) for diabetes relative to the first quintile (p<0.0001 for trend). Significant trends in association were still observed after adjustment for BMI (RR 1.44 [1.15-1.80], p<0.0001 for trend) and adiponectin levels (RR 1.28 [1.02-1.60], p=0.006 for trend). Further adjustment for inflammatory markers in a sub-sample did not significantly change the results. Elevated IL-18 levels are associated with higher risk of diabetes. This association is independent of usual risk factors, including BMI and adipokine levels.
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作者：
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DOI：
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