Yilmaz Mahmut Ilker, Saglam Mutlu, Qureshi Abdul Rashid, Carrero Juan Jesus, Caglar Kayser, Eyileten Tayfun, Sonmez Alper, Cakir Erdinc, Oguz Yusuf, Vural Abdulgaffar, Yenicesu Mujdat, Stenvinkel Peter, Lindholm Bengt, Axelsson Jonas
Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, K56 Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
Nephrol Dial Transplant. 2008 May;23(5):1621-7. doi: 10.1093/ndt/gfm828. Epub 2008 Jan 5.
Type-2 diabetes and diabetic kidney disease have additive effects on cardiovascular risk. Furthermore, the degree of proteinuria is an independent predictor of mortality in this patient group. We hypothesized that altered kidney clearance and/or metabolism of vasoactive peptides occurring during proteinuria could link early diabetic nephropathy to cardio vascular disease (CVD).
We performed a cross-sectional study of 85 incident patients (51 +/- 5 years, 49 males) with type-2 diabetes and 38 age- and sex-matched controls. We further divided patients by the presence of minor (<500 mg/day; n = 40) or severe (>/=500 mg/day; n = 45) proteinuria. Clinical and anthropometric data, along with ultrasonographic flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thicknesses (CIMT), were recorded in each group. Circulating NAMPT/visfatin, adiponectin (normalized to BMI), AHSG/fetuin-A and hsCRP levels were also measured using commercial ELISA.
Plasma NAMPT/visfatin, CIMT, HOMA index and hsCRP levels were all significantly higher in diabetics than in control subjects, and all but CIMT correlated with proteinuria (rho = 0.46; P < 0.001, rho = 0.54; P > 0.05, rho = 0.32; P = 0.003, rho = 0.76; P < 0.001, respectively). FMD, adiponectin and AHSG/fetuin-A levels were significantly lower, and negatively correlated with proteinuria (rho = -0.54; P < 0.001, rho = -0.56; P < 0.001, rho = -0.48; P < 0.001, respectively). In a multivariate regression analysis, the degrees of proteinuria (r(2) = -0.32, P = 0.04) and plasma levels of NAMPT/visfatin (r(2) = -0.33, P = 0.006) were independently related to FMD.
The present study suggests that the presence of proteinuria, regardless of the degree of renal function impairment, is an important predictor of endothelial dysfunction in early diabetic nephropathy and that it is associated with altered circulating levels of NAMPT/visfatin and adiponectin.
2型糖尿病和糖尿病肾病对心血管风险具有累加效应。此外，蛋白尿程度是该患者群体死亡率的独立预测因素。我们推测，蛋白尿期间发生的血管活性肽肾脏清除和/或代谢改变可能将早期糖尿病肾病与心血管疾病（CVD）联系起来。
我们对85例2型糖尿病初发患者（51±5岁，49例男性）和38例年龄及性别匹配的对照者进行了一项横断面研究。我们根据是否存在少量（<500mg/天；n = 40）或大量（≥500mg/天；n = 45）蛋白尿对患者进一步分组。记录了每组的临床和人体测量数据，以及肱动脉超声血流介导的扩张（FMD）和颈动脉内膜中层厚度（CIMT）。还使用商业ELISA法测量了循环中的NAMPT/内脂素、脂联素（根据BMI进行标准化）、AHSG/胎球蛋白-A和hsCRP水平。
糖尿病患者的血浆NAMPT/内脂素、CIMT、HOMA指数和hsCRP水平均显著高于对照组，除CIMT外，所有指标均与蛋白尿相关（相关系数分别为0.46；P < 0.001、0.54；P > 0.05、0.32；P = 0.003、0.76；P < 0.001）。FMD、脂联素和AHSG/胎球蛋白-A水平显著降低，且与蛋白尿呈负相关（相关系数分别为-0.54；P < 0.001、-0.56；P < 0.001、-0.48；P < 0.001）。在多变量回归分析中，蛋白尿程度（r² = -0.32，P = 0.04）和血浆NAMPT/内脂素水平（r² = -0.33，P = 0.006）与FMD独立相关。
本研究表明，无论肾功能损害程度如何，蛋白尿的存在都是早期糖尿病肾病内皮功能障碍的重要预测因素，并且它与循环中NAMPT/内脂素和脂联素水平的改变有关。
