Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus
Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus
复制标题
DOI：
10.1001/jama.291.16.1978
复制
发表时间：
2004-04-28
影响因子：
120.7
通讯作者：
Manson, JE
中科院分区：
文献类型：
--
作者：
Meigs, JB;Hu, FB;Manson, JE
目的确定反映内皮功能障碍的血浆生物标志物(E-选择素、细胞间黏附分子-1和血管细胞黏附分子-1)水平升高是否能预测最初非糖尿病女性发生2型糖尿病的可能性。设计和设置前瞻性嵌套病例对照研究，在护士健康研究中进行，该研究始于1976年。在121700名最初登记的女性中，32826人在1989年至1990年提供了血样；在基线没有糖尿病、心血管疾病或癌症的人中，有737人在2000年发生了糖尿病。对照组(n=785)根据匹配的年龄、空腹状态和种族进行选择。主要结果通过E-选择素、ICAM-1和VCAM-1的基线水平来衡量临床确诊的2型糖尿病的风险。结果E-选择素、细胞间黏附分子-1、血管细胞黏附分子-1、血管细胞黏附分子-1、血管细胞黏附分子-1的基线中位数分别为61.2vs45.4ngL、264.9 ngmLvs247.0、545.4 ngmLvs526.0 ng/mLP均小于或等于0.004。在Logistic回归模型中，E-选择素和ICAM-1水平升高可预测糖尿病的发生，该模型以匹配标准为条件，并对体重指数(BMI)、糖尿病家族史、吸烟、饮食评分、饮酒、活动指数和绝经后激素使用进行了调整。高五分位数与低五分位数发生糖尿病的调整后相对风险分别为：E-选择素5.43(95%可信区间，3.47-8.50)，ICAM-1 3.56(95%CI，2.28-5.58)，VCAM-1 1.12(95%CI，0.76-1.66)。调整腰围而不是体重指数，或进一步调整C反应蛋白、空腹胰岛素和血红蛋白A(1c)的基线水平，或排除在前4年随访中确诊的病例，都不会改变这些关联。结论内皮功能障碍预测女性2型糖尿病与其他已知的危险因素无关，包括肥胖和亚临床炎症。
Context Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes.Objective To determine whether elevated plasma levels of biomarkers reflecting endothelial dysfunction (E-selectin; intercellular adhesion molecule 1 [ICAM-1]; and vascular cell adhesion molecule 1 [VCAM-1]) predict development of type 2 diabetes in initially nondiabetic women.Design and Setting Prospective, nested case-control study within the Nurses' Health Study, an ongoing US study initiated in 1976.Participants Of 121700 women initially enrolled, 32826 provided blood samples in 1989-1990; of those free of diabetes, cardiovascular disease, or cancer at baseline, 737 developed incident diabetes by 2000. Controls (n = 785) were selected according to matched age, fasting status, and race.Main Outcome Measure Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels of E-selectin, ICAM-1, and VCAM-1. Results Baseline median levels of the biomarkers were significantly higher among cases than among controls (E-selectin, 61.2 vs 45.4 ng/mL; ICAM-1, 264.9 vs 247.0 ng/mL; VCAM-1, 545.4 vs 526.0 ng/mL [all P values less than or equal to .004]). Elevated E-selectin and ICAM-1 levels predicted incident diabetes in logistic regression models conditioned on matching criteria and adjusted for body mass index (BMI), family history of diabetes, smoking, diet score, alcohol intake, activity index, and postmenopausal hormone use. The adjusted relative risks for incident diabetes in the top quintile vs the bottom quintiles were 5.43 for E-selectin (95% confidence interval [CI], 3.47-8.50), 3.56 for ICAM-1 (95% Cl, 2.28-5.58), and 1.12 for VCAM-1 (95% Cl, 0.76-1.66). Adjustment for waist circumference instead of BMI or further adjustment for baseline levels of C-reactive protein, fasting insulin, and hemoglobin A(1c) or exclusion of cases diagnosed during the first 4 years of follow-up did not alter these associations.Conclusion Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors, including obesity and subclinical inflammation.