Meigs James B, Hu Frank B, Rifai Nader, Manson JoAnn E
General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Mass 02114, USA.
JAMA. 2004 Apr 28;291(16):1978-86. doi: 10.1001/jama.291.16.1978.
Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes.
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.
Prospective, nested case-control study within the Nurses' Health Study, an ongoing US study initiated in 1976.
Of 121 700 women initially enrolled, 32 826 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.
Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels of E-selectin, ICAM-1, and VCAM-1.
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 < or =.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% CI, 2.28-5.58), and 1.12 for VCAM-1 (95% CI, 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.
Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors, including obesity and subclinical inflammation.
内皮功能障碍在已确诊的2型糖尿病患者中存在，但也可能在糖尿病发生之前出现。
确定反映内皮功能障碍的生物标志物（E-选择素、细胞间黏附分子1[ICAM-1]和血管细胞黏附分子1[VCAM-1]）血浆水平升高是否可预测初诊非糖尿病女性发生2型糖尿病。
在美国护士健康研究（一项始于1976年的正在进行的研究）中进行的前瞻性巢式病例对照研究。
最初纳入的121700名女性中，32826名在1989 - 1990年提供了血样；在基线时无糖尿病、心血管疾病或癌症的女性中，到2000年有737人发生了新发糖尿病。根据年龄、空腹状态和种族匹配选择了785名对照。
根据E-选择素、ICAM-1和VCAM-1的基线水平确定确诊临床诊断2型糖尿病的风险。
病例组生物标志物的基线中位数水平显著高于对照组（E-选择素：61.2对45.4 ng/mL；ICAM-1：264.9对247.0 ng/mL；VCAM-1：545.4对526.0 ng/mL[所有P值≤0.004]）。在以匹配标准为条件并根据体重指数（BMI）、糖尿病家族史、吸烟、饮食评分、饮酒量、活动指数和绝经后激素使用情况进行调整的逻辑回归模型中，E-选择素和ICAM-1水平升高可预测新发糖尿病。最高五分位数与最低五分位数相比，新发糖尿病的调整后相对风险分别为：E-选择素5.43（95%置信区间[CI]，3.47 - 8.50），ICAM-1 3.56（95%CI，2.28 - 5.58），VCAM-1 1.12（95%CI，0.76 - l.66）。用腰围代替BMI进行调整，或进一步根据C反应蛋白、空腹胰岛素和糖化血红蛋白A1c的基线水平进行调整，或排除随访前4年诊断的病例，均未改变这些关联。
内皮功能障碍可独立于其他已知风险因素（包括肥胖和亚临床炎症）预测女性2型糖尿病。
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