Department of Medicine and Laboratory Services, Medical University of South Carolina and Ralph H Johnson VA Medical Center, Charleston, South Carolina, USA.
Diabetes Care. 2013 Aug;36(8):2317-23. doi: 10.2337/dc12-2521. Epub 2013 Mar 20.
The current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria.
Levels of inflammation and endothelial cell dysfunction biomarkers were measured in 1,237 of 1,441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline. To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, micro-, and macroalbuminuria were the outcomes of interest.
In the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and -2 lead to a 30-50% increase in the odds to develop macroalbuminuria. Following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and -2 but not for IL-6 or PAI-1.
Our study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and -2, are important predictors of macroalbuminuria in patients with type 1 diabetes.
本研究旨在探讨糖尿病控制和并发症试验（DCCT）/糖尿病干预和并发症的流行病学队列中，基线时 DCCT 采集的样本中炎症和内皮功能障碍标志物水平是否异常，是否可以预测白蛋白尿的发生。
在基线时既无白蛋白尿也无心血管疾病的 1441 名 DCCT 研究患者中，有 1237 名患者检测了炎症和内皮细胞功能障碍生物标志物的水平。为了检验生物标志物与白蛋白尿的相关性，使用广义逻辑回归模型来量化生物标志物水平升高与异常白蛋白尿发生之间的相关性。正常、微量和大量白蛋白尿是感兴趣的结局。
在调整了 DCCT 治疗分配、基线白蛋白排泄率和 ACE/血管紧张素受体阻滞剂药物使用的逻辑回归模型中，标准化可溶性 E-选择素（sE-选择素）水平每增加一个单位，发展为大量白蛋白尿的几率增加 87%，而白细胞介素-6（IL-6）、纤溶酶原激活物抑制剂 1（PAI-1；总和活性）和可溶性肿瘤坏死因子受体（TNFR）-1 和 -2 的水平每增加一个单位，发展为大量白蛋白尿的几率增加 30%-50%。在调整了 DCCT 基线视网膜病变状态、年龄、性别、HbA1c 和糖尿病病程后，sE-选择素和 TNFR-1 和 -2 仍有显著相关性，但 IL-6 或 PAI-1 无显著相关性。
我们的研究表明，高水平的炎症标志物，主要是 E-选择素和 sTNFR-1 和 -2，是 1 型糖尿病患者发生大量白蛋白尿的重要预测因子。
