Plasma α-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients
Plasma α-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients
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DOI：
10.1210/jc.2007-1910
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发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Frystyk, Jan
中科院分区：
文献类型：
--
作者：
Joseph, Gowsini;Tarnow, Lise;Frystyk, Jan
背景：α -防御素是先天免疫系统的抗菌肽。此外，实验证据表明-防御素具有促动脉粥样硬化的作用。目的：研究血浆α -防御素作为1型糖尿病患者心血管疾病（CVD）临床标志物的预测价值。方法：在一项观察性、前瞻性设计中，389例长期1型糖尿病患者在研究开始时（1993年，基线）接受了心血管疾病检查，并通过丹麦国家登记册进行了中位10.1年（范围0.2-10.4年）的随访。1993年收集血浆，保存在-80℃，直到使用内部RIA分析血浆α -防御素。结果：在基线时，肾病患者血浆α -防御素显著高于无肾病患者[中位数和四分位数范围：305 (205-321)vs 223 (182-263) mu g/l；P < 0.0001]。随访期间，98例患者达到了主要终点（CVD致死性和非致死性事件）。前瞻性地，上、下三分位数的基线α -防御素显著增加了协变量调整后cvd相关发病率和死亡率的风险，风险比为2.8(1.3-5.9)（中位数和95%置信区间，P = 0.006）。结论：本研究提示血浆α -防御素可作为1型糖尿病患者cvd相关发病率和死亡率的临床危险标志物。然而，未来的研究需要澄清血浆α -防御素是否与CVD的发展有因果关系，或者是一个无辜的旁观者。
Context: alpha-Defensins are antimicrobial peptides of the innate immune system. In addition, experimental evidence suggests that alpha-defensins are proatherogenic.Objective: The objective of the study was to examine the predictive value of plasma alpha-defensin as a clinical marker of cardiovascular disease (CVD) in patients with type 1 diabetes.Methods: In an observational, prospective design, 389 patients with long-lasting type 1 diabetes were examined for CVD at study start (1993; baseline) and followed up through the Danish National Register for a median of 10.1 yr (range 0.2-10.4 yr). Plasma was collected in 1993 and stored at -80 C until analysis of plasma alpha-defensin using an in-house RIA.Results: At baseline, plasma alpha-defensin was significantly higher in patients with than without nephropathy [median and interquartile ranges: 305 (205-321) vs. 223 (182-263) mu g/liter; P < 0.0001]. During follow-up, 98 patients reached the primary end point (fatal and nonfatal events of CVD). Prospectively a baseline alpha-defensin within the upper vs. the lower tertile significantly increased the covariate-adjusted risk for CVD-related morbidity and mortality to a hazard ratio of 2.8 (1.3-5.9) (median and 95% confidence intervals, P = 0.006).Conclusion: This study suggests that plasma alpha-defensin may serve as a clinical risk marker for CVD-related morbidity and mortality in type 1 diabetes. However, future studies are needed to clarify whether plasma alpha-defensin is causally linked to the development of CVD or an innocent bystander.