Baseline markers of inflammation are associated with progression to macroalbuminuria in type 1 diabetic subjects.
Baseline markers of inflammation are associated with progression to macroalbuminuria in type 1 diabetic subjects.
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DOI：
10.2337/dc12-2521
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发表时间：
2013-08
期刊：
影响因子：
16.2
通讯作者：
DCCT/EDIC Research Group
中科院分区：
文献类型：
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作者：
Lopes-Virella MF;Baker NL;Hunt KJ;Cleary PA;Klein R;Virella G;DCCT/EDIC Research Group
本研究旨在确定糖尿病控制和并发症试验（DCCT）/糖尿病干预和并发症流行病学队列中，DCCT基线时采集的样本中测量的炎症和内皮功能障碍标志物的异常水平是否能够预测大量白蛋白尿的发生。在DCCT研究中招募的1，441名患者中，测量了1，237名患者的炎症和内皮细胞功能障碍生物标志物水平，这些患者在基线时均无白蛋白尿和心血管疾病。为了测试对数转换的生物标志物与白蛋白尿的关联，使用广义逻辑回归模型来量化生物标志物水平增加与异常白蛋白尿发展的关联。正常、微量和大量白蛋白尿是关注的结果。在经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调整的logistic回归模型中，可溶性E-选择素标准化水平增加一个单位，（可溶性E-选择素）与发生大量白蛋白尿的几率增加87%和白细胞介素-6（IL-6）、纤溶酶原激活物抑制剂1（PAI-1）水平增加1个单位相关。（派-1;总的和活性的）和可溶性肿瘤坏死因子受体（TNFR）-1和-2导致发生大量白蛋白尿的几率增加30-50%。校正DCCT基线视网膜病变状态、年龄、性别、HbA 1c和糖尿病病程后，sE-选择素与TNFR-1和TNFR-2仍存在显著相关性，但与IL-6或派-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sTNRF-1和-2，是1型糖尿病患者大量白蛋白尿的重要预测因子。
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.