von Eynatten Maximilian, Liu Dan, Hock Cornelia, Oikonomou Dimitrios, Baumann Marcus, Allolio Bruno, Korosoglou Grigorios, Morcos Michael, Campean Valentina, Amann Kerstin, Lutz Jens, Heemann Uwe, Nawroth Peter P, Bierhaus Angelika, Humpert Per M
Department of Nephrology, Technische Universitat Muenchen, Munich, Germany.
Diabetes. 2009 Sep;58(9):2093-9. doi: 10.2337/db09-0204. Epub 2009 Jun 9.
Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes.
Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT).
A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms ( approximately 30-70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 +/- 14.26 vs. control subjects: 2.91 +/- 3.85 microg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (beta = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007).
Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events.
可靠识别糖尿病患者血管损伤及风险的标志物很少见，且关于血清脂联素与大血管疾病关联的报道并不一致。与现有血清脂联素数据不同，本研究评估尿脂联素排泄是否可能是2型糖尿病中更一致的血管损伤标志物。
通过免疫组织化学评估人肾活检组织中脂联素的分布，并用蛋白质印迹分析对尿脂联素异构体进行表征。采用酶联免疫吸附测定法测量了156例有糖尿病肾病病史的2型糖尿病患者和40例健康对照者的尿脂联素总排泄率。通过颈总动脉内膜中层厚度（IMT）评估动脉粥样硬化负担。
在非糖尿病肾的肾小球毛细血管和肾内小动脉的内皮表面发现脂联素均匀染色，而在糖尿病肾病中染色减少。通过蛋白质印迹分析在尿液中检测到低分子脂联素异构体（约30 - 70 kDa）。2型糖尿病患者的尿脂联素显著增加（7.68±14.26 vs. 对照者：2.91±3.85μg/g肌酐，P = 0.008）。在2型糖尿病患者中，尿脂联素与IMT相关（r = 0.479，P < 0.001），并且在多变量回归分析中被证明是IMT的有力独立预测因子（β = 0.360，P < 0.001）。在一个包括英国前瞻性糖尿病研究冠心病风险引擎变量的风险预测模型中，尿脂联素而非白蛋白排泄率，为预测IMT增加增加了显著价值（P = 0.007）。
尿脂联素排泄量的量化似乎是血管损伤的独立指标，可能识别血管事件风险增加。
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