Astrup Anne Sofie, Tarnow Lise, Pietraszek Lotte, Schalkwijk Casper G, Stehouwer Coen D A, Parving Hans-Henrik, Rossing Peter
Steno Diabetes Center, Gentofte, Denmark.
Diabetes Care. 2008 Jun;31(6):1170-6. doi: 10.2337/dc07-1960. Epub 2008 Mar 10.
We evaluated the association of biomarkers of endothelial dysfunction and inflammation with all-cause mortality and cardiovascular mortality and morbidity and decline in glomerular filtration rate (GFR) in type 1 diabetic patients.
We prospectively followed 199 type 1 diabetic patients with diabetic nephropathy and 192 patients with persistent normoalbuminuria. Biomarkers were measured at baseline.
We constructed two Z scores: the mean inflammatory Z score combined C-reactive protein, interleukin-6, soluble intercellular adhesion molecule (sICAM-1), and secreted phospholipase A2 and the mean Z score for endothelial dysfunction combined soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1, and sICAM-1. The mean Z score of inflammatory biomarkers was associated with mortality and the combined end point in patients with diabetic nephropathy after multivariate adjustment (hazard ratio 1.7 [95% CI 1.1-2.6]; P = 0.025 and 1.5 [1.1-2.2]; P = 0.017). The mean Z score for endothelial dysfunction biomarkers was associated with mortality in a model adjusting for age and sex in patients with diabetic nephropathy (1.6 [1.0-2.3]; P = 0.031). The mean Z score for endothelial dysfunction correlated with decline in GFR (r = -0.243; P = 0.001); the correlation persisted after multivariate adjustment (coefficient -1.38 [95% CI -2.27 to -0.50]; P = 0.002).
Mean Z scores of inflammatory biomarkers are significantly associated with all-cause mortality and cardiovascular morbidity and mortality in patients with nephropathy after multivariate adjustment. These data suggest that the high risk of cardiovascular disease in type 1 diabetes may be explained in part by inflammatory activity. Mean Z score of endothelial dysfunction correlated after multivariate adjustment with the rate of decline in GFR.
我们评估了1型糖尿病患者内皮功能障碍和炎症生物标志物与全因死亡率、心血管死亡率及发病率以及肾小球滤过率（GFR）下降之间的关联。
我们对199例患有糖尿病肾病的1型糖尿病患者和192例持续性正常白蛋白尿患者进行了前瞻性随访。在基线时测量生物标志物。
我们构建了两个Z评分：平均炎症Z评分综合了C反应蛋白、白细胞介素-6、可溶性细胞间黏附分子（sICAM-1）和分泌型磷脂酶A2；平均内皮功能障碍Z评分综合了可溶性血管细胞黏附分子1、纤溶酶原激活物抑制剂-1和sICAM-1。多变量调整后，炎症生物标志物的平均Z评分与糖尿病肾病患者的死亡率及联合终点相关（风险比1.7 [95%可信区间1.1 - 2.6]；P = 0.025以及1.5 [1.1 - 2.2]；P = 0.017）。在针对糖尿病肾病患者的年龄和性别进行调整的模型中，内皮功能障碍生物标志物的平均Z评分与死亡率相关（1.6 [1.0 - 2.3]；P = 0.031）。内皮功能障碍的平均Z评分与GFR下降相关（r = -0.243；P = 0.001）；多变量调整后该相关性依然存在（系数 -1.38 [95%可信区间 -2.27至 -0.50]；P = 0.002）。
多变量调整后，炎症生物标志物的平均Z评分与肾病患者的全因死亡率、心血管发病率及死亡率显著相关。这些数据表明，1型糖尿病患者心血管疾病的高风险可能部分由炎症活动来解释。多变量调整后，内皮功能障碍的平均Z评分与GFR下降速率相关。
