Meigs James B, O'donnell Christopher J, Tofler Geoffrey H, Benjamin Emelia J, Fox Caroline S, Lipinska Izabela, Nathan David M, Sullivan Lisa M, D'Agostino Ralph B, Wilson Peter W F
General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, USA.
Diabetes. 2006 Feb;55(2):530-7. doi: 10.2337/diabetes.55.02.06.db05-1041.
Endothelial dysfunction may precede development of type 2 diabetes. We tested the hypothesis that elevated levels of hemostatic markers of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) antigen, and von Willebrand factor (vWF) antigen predicted incident diabetes independent of other diabetes risk factors. We followed 2,924 Framingham Offspring subjects (54% women, mean age 54 years) without diabetes at baseline (defined by treatment, fasting plasma glucose > or =7 or 2-h postchallenge glucose > or =11.1 mmol/l) over 7 years for new cases of diabetes (treatment or fasting plasma glucose > or =7.0 mmol/l). We used a series of regression models to estimate relative risks for diabetes per interquartile range (IQR) increase in PAI-1 (IQR 16.8 ng/ml) and vWF (IQR 66.8% of control) conditioned on baseline characteristics. Over follow-up, there were 153 new cases of diabetes. Age- and sex-adjusted relative risks of diabetes were 1.55 per IQR for PAI-1 (95% CI 1.41-1.70) and 1.49 for vWF (1.21-1.85). These effects remained after further adjustment for diabetes risk factors (including physical activity; HDL cholesterol, triglyceride, and blood pressure levels; smoking; parental history of diabetes; use of alcohol, nonsteroidal anti-inflammatory drugs, exogenous estrogen, or hypertension therapy; and impaired glucose tolerance), waist circumference, homeostasis model assessment of insulin resistance, and inflammation (assessed by levels of C-reactive protein): the adjusted relative risks were 1.18 per IQR for PAI-1 (1.01-1.37) and 1.39 for vWF (1.09-1.77). We conclude that in this community-based sample, plasma markers of endothelial dysfunction increased risk of incident diabetes independent of other diabetes risk factors including obesity, insulin resistance, and inflammation.
内皮功能障碍可能先于2型糖尿病的发生。我们检验了这样一个假设：内皮功能障碍的止血标志物纤溶酶原激活物抑制剂-1（PAI-1）抗原和血管性血友病因子（vWF）抗原水平升高可独立于其他糖尿病危险因素预测糖尿病的发生。我们对2924名弗雷明汉后代研究对象（54%为女性，平均年龄54岁）进行了为期7年的随访，这些对象在基线时无糖尿病（根据治疗情况定义，空腹血糖≥7或餐后2小时血糖≥11.1 mmol/l），观察新发生的糖尿病病例（治疗或空腹血糖≥7.0 mmol/l）。我们使用一系列回归模型来估计在以基线特征为条件的情况下，PAI-1（四分位数间距[IQR]为16.8 ng/ml）和vWF（IQR为对照的66.8%）每增加一个四分位数间距，患糖尿病的相对风险。在随访期间，有153例新发生的糖尿病病例。经年龄和性别调整后，PAI-1每增加一个四分位数间距，糖尿病的相对风险为1.55（95%可信区间为1.41 - 1.70），vWF为1.49（1.21 - 1.85）。在进一步调整糖尿病危险因素（包括身体活动；高密度脂蛋白胆固醇、甘油三酯和血压水平；吸烟；糖尿病家族史；酒精、非甾体抗炎药、外源性雌激素或高血压治疗的使用情况；以及糖耐量受损）、腰围、胰岛素抵抗的稳态模型评估和炎症（通过C反应蛋白水平评估）后，这些效应仍然存在：调整后的相对风险为PAI-1每增加一个四分位数间距为1.18（1.01 - 1.37），vWF为1.39（1.09 - 1.77）。我们得出结论，在这个基于社区的样本中，内皮功能障碍的血浆标志物可独立于包括肥胖、胰岛素抵抗和炎症在内的其他糖尿病危险因素增加糖尿病发生的风险。
