Saraheimo M, Teppo A-M, Forsblom C, Fagerudd J, Groop P-H
Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, and Folkhälsan Research Centre, Bimedicum Helsinki, University of Helsinki, Finland.
Diabetologia. 2003 Oct;46(10):1402-7. doi: 10.1007/s00125-003-1194-5. Epub 2003 Aug 20.
AIMS/HYPOTHESIS: Increased concentrations of C-reactive protein and interleukin-6, a finding suggestive of the presence of inflammation, have been observed in Type 2 diabetes. In such patients, C-reactive protein was predictive of diabetic nephropathy. Studies on low-grade inflammatory markers and nephropathy in Type 1 diabetic patients have shown conflicting results. Therefore we studied whether low-grade inflammation is associated with diabetic nephropathy in Type 1 diabetic patients.
We divided 194 Type 1 diabetic patients into three groups from the Finnish Diabetic Nephropathy Study based upon their albumin excretion rate. Patients with normoalbuminuria (n=67) had no antihypertensive medication or signs of cardiovascular disease, while patients with microalbuminuria (n=64) or macroalbuminuria (n=63) were all treated with an angiotensin-converting enzyme inhibitor, a drug that could attenuate low-grade inflammation. As a measure of insulin sensitivity we used estimated glucose disposal rate. C-reactive protein was measured by radioimmunoassay and interleukin-6 by high sensitivity enzyme immunoassay.
C-reactive protein was higher in micro- and macroalbuminuric patients compared to normoalbuminuric patients (normoalbuminuria 2.0+/-1.7, microalbuminuria 2.6+/-1.7, macroalbuminuria 2.9+/-2.5 mg/l; p=0.016), while interleukin-6 increased in parallel with the severity of the renal disease (1.9+/-1.5, 2.9+/-3.3, 3.6+/-3.1 ng/l; p<0.0001). In multiple regression analysis albumin excretion rate was the only variable independently associated with C-reactive protein (p=0.03), whereas albumin excretion rate (p=0.0003), HDL-cholesterol (p=0.0135) and duration of diabetes (p=0.0176) were independently associated with interleukin-6.
CONCLUSIONS/INTERPRETATION: Low-grade inflammatory markers are associated with diabetic nephropathy in Type 1 diabetic patients. The predictive value needs to be assessed.
目的/假设：在2型糖尿病患者中，已观察到C反应蛋白和白细胞介素-6浓度升高，这一发现提示存在炎症。在此类患者中，C反应蛋白可预测糖尿病肾病。关于1型糖尿病患者低度炎症标志物与肾病的研究结果相互矛盾。因此，我们研究了低度炎症是否与1型糖尿病患者的糖尿病肾病相关。
我们根据白蛋白排泄率，将来自芬兰糖尿病肾病研究的194例1型糖尿病患者分为三组。正常白蛋白尿患者（n = 67）未服用抗高血压药物，也无心血管疾病迹象，而微量白蛋白尿患者（n = 64）或大量白蛋白尿患者（n = 63）均接受血管紧张素转换酶抑制剂治疗，该药物可减轻低度炎症。作为胰岛素敏感性的指标，我们使用估计的葡萄糖处置率。通过放射免疫分析法测定C反应蛋白，通过高灵敏度酶免疫分析法测定白细胞介素-6。
与正常白蛋白尿患者相比，微量和大量白蛋白尿患者的C反应蛋白更高（正常白蛋白尿组2.0±1.7，微量白蛋白尿组2.6±1.7，大量白蛋白尿组2.9±2.5 mg/l；p = 0.016），而白细胞介素-6随肾病严重程度平行升高（1.9±1.5，2.9±3.3，3.6±3.1 ng/l；p < 0.0001）。在多元回归分析中，白蛋白排泄率是与C反应蛋白独立相关的唯一变量（p = 0.03），而白蛋白排泄率（p = 0.0003）、高密度脂蛋白胆固醇（p = 0.·0135）和糖尿病病程（p = 0.0176）与白细胞介素-6独立相关。
结论/解读：低度炎症标志物与1型糖尿病患者的糖尿病肾病相关。其预测价值有待评估。
