Department of Pathophysiology and Endocrinology, Medical University of Silesia, Poland.
Clin Exp Med. 2010 Sep;10(3):185-92. doi: 10.1007/s10238-009-0084-7. Epub 2009 Dec 11.
The aim of this study was to evaluate the ferric-reducing ability of serum (FRAS), paraoxonase 1 (PON1), ceruloplasmin serum oxidase activity and hsCRP level in patients with type1 diabetes mellitus without and with diabetic retinopathy. The study was performed in 76 patients with type 1 diabetes mellitus, 35 without diabetic retinopathy (group 1) and 41 with preproliferative and proliferative retinopathy (group 2). Control group consisted of 35 nondiabetic, age-, gender-, body mass-matched healthy volunteers who came to the outpatient clinic for a routine health check-up. We evaluated FRAS using the method described by Benzie and Strain; PON1 by kinetic spectrophotometric assay with paraoxon as substrate and ceruloplasmin using its oxidative activity with 3-phenylenodiamine as substrate. CRP was measured with a high sensitive enzyme immunoassay. PON1 activity was significantly decreased in patients with diabetic retinopathy (227.66 +/- 123.57 U/l) when compared with control (312.04 +/- 129.77 U/l). FRAS was significantly decreased in group 2 (439.33 +/- 79.87 micromol/l) when compared with group 1 (522.79 +/- 167.56 micromol/l) and control (529.80 +/- 81.99 micromol/l). Ceruloplasmin activity was significantly elevated in group 1 (58.36 +/- 22.56 U/g protein) when compared with control (45.22 +/- 14.96 U/g protein). We have found significant increase in hsCRP level in group 2 (3.71 +/- 2.47 mg/l) when compared with group 1 (1.75 +/- 1.01 mg/l) and control (0.57 +/- 0.46 mg/l). The PON1/CRP ratio in control group was significantly increased when compared with diabetic patients and was significantly decreased in group 2 compared with group 1. We have not found gender-dependent difference in studied parameters in both control and in study groups. We have found tendency to decrease the serum activity of FRAS and hsCRP in elder patients but the difference was significant only in group 2. FRAS and PON 1 activity is decreased in patients with type 1 diabetes mellitus with presence of diabetic retinopathy which confirms that oxidative stress could play a role in pathogenesis of diabetic retinopathy. Significantly elevated levels of hsCRP in diabetic patients with the presence of diabetic retinopathy compared with patients without diabetic retinopathy providing a link between inflammation and the development of microvascular complication of diabetes. Because of the significant difference in PON1/CRP ratio between patients without and with the presence of diabetic retinopathy, it seems that PON1:CRP ratio may be used as a biochemical marker for progression of retinopathy. The link between the antioxidant concentration, inflammation and the development of diabetes complications needs further longitudinal studies in order to confirm our findings.
本研究旨在评估血清铁还原能力（FRAS）、对氧磷酶 1（PON1）、铜蓝蛋白血清氧化酶活性和高敏 C 反应蛋白（hsCRP）水平在 1 型糖尿病患者无和有糖尿病视网膜病变中的变化。该研究纳入了 76 例 1 型糖尿病患者，其中 35 例无糖尿病视网膜病变（组 1），41 例有增殖前期和增殖期视网膜病变（组 2）。对照组由 35 例年龄、性别、体重匹配的非糖尿病健康志愿者组成，他们因常规健康检查而来到门诊。我们采用 Benzie 和 Strain 描述的方法评估 FRAS；通过动力学分光光度法测定 PON1 活性，以对氧磷为底物，用 3-苯并二胺作为底物测定铜蓝蛋白的氧化活性。hsCRP 采用高敏酶免疫法测定。与对照组（312.04 ± 129.77 U/L）相比，糖尿病视网膜病变患者的 PON1 活性明显降低（227.66 ± 123.57 U/L）。与组 1（522.79 ± 167.56 μmol/L）和对照组（529.80 ± 81.99 μmol/L）相比，组 2（439.33 ± 79.87 μmol/L）的 FRAS 明显降低。与对照组（45.22 ± 14.96 U/g 蛋白）相比，组 1 的铜蓝蛋白活性显著升高（58.36 ± 22.56 U/g 蛋白）。与组 1（1.75 ± 1.01 mg/L）和对照组（0.57 ± 0.46 mg/L）相比，组 2 的 hsCRP 水平显著升高（3.71 ± 2.47 mg/L）。与糖尿病患者相比，对照组的 PON1/CRP 比值明显升高，与组 1 相比，组 2 的 PON1/CRP 比值明显降低。我们在对照组和研究组中均未发现性别依赖性的研究参数差异。我们发现 FRAS 和 hsCRP 的血清活性在老年患者中呈下降趋势，但仅在组 2 中差异具有统计学意义。1 型糖尿病患者有糖尿病视网膜病变时，FRAS 和 PON1 活性降低，证实氧化应激可能在糖尿病视网膜病变的发病机制中起作用。与无糖尿病视网膜病变的患者相比，有糖尿病视网膜病变的糖尿病患者的 hsCRP 水平显著升高，提示炎症与糖尿病微血管并发症的发生之间存在联系。由于无和有糖尿病视网膜病变患者的 PON1/CRP 比值存在显著差异，因此 PON1:CRP 比值似乎可作为视网膜病变进展的生化标志物。为了证实我们的发现，需要进一步进行关于抗氧化剂浓度、炎症与糖尿病并发症发展之间关系的纵向研究。
