Department of Nephrology, Victor Babes University of Medicine and Pharmacy, County Emergency Hospital Timisoara, Romania.
Wien Klin Wochenschr. 2009;121(23-24):765-75. doi: 10.1007/s00508-009-1279-3.
Thiazolidinediones represent a novel class of drugs that exert pleiotropic effects at various levels and lower blood glucose through reduction of insulin resistance in patients with type 2 diabetes mellitus.
The nephro- and neuroprotective effects of rosiglitazone vs. glimepiride were evaluated in normoalbuminuric patients with type 2 diabetes mellitus. The relevance of several biomarkers in the diagnosis of incipient diabetic nephropathy and cerebral microangiopathy was also assessed.
A total of 34 normoalbuminuric patients with type 2 diabetes mellitus were enrolled in a 1-year open-label randomized controlled trial. Group A comprised 17 patients (7 men, 10 women, mean age 63 +/- 8.07 years) treated with rosiglitazone plus metformin; Group B comprised 17 patients (7 men, 10 women, mean age 63.2 +/- 7.19 years) treated with glimepiride plus metformin. All patients were assessed at initiation, at 6 months and by the end of the study concerning serum and urinary beta2-microglobulin, urinary a1-microglobulin, serum cystatin C, serum creatinine, glomerular filtration rate, C-reactive protein, fibrinogen, glycated hemoglobin, cholesterol, triglycerides, hemoglobin, and the urinary albumin/creatinine ratio (UACR). Cerebral hemodynamic parameters were also measured: pulsatility index and resistance index in the internal carotid artery and middle cerebral artery, and intima-media thickness in the common carotid artery.
At 1 year there were differences between groups A and B regarding serum cystatin C (P < 0.04), urinary beta2-microglobulin (P < 0.004), urinary a1-microglobulin (P < 0.0001), C-reactive protein (P < 0.0001), fibrinogen (P < 0.0001), serum creatinine (P < 0.0024), glomerular filtration rate (P < 0.0010), UACR (P < 0.0001), and the cerebral hemodynamic indices. The increase in a1- and beta2-microglobulin preceded the occurrence of microalbuminuria. UACR correlated with urinary a1- microglobulin (r = 0.4854), urinary beta2-microglobulin (r = 0.4867), and serum cystatin C (r = 0.3702). The cerebrovascular parameters improved in group A vs. group B and correlated with urinary beta2- and a1-microglobulin, C-reactive protein, fibrinogen, glomerular filtration rate, and duration of diabetes.
Rosiglitazone demonstrated its nephro- and neuroprotective effects in normoalbuminuric patients with type 2 diabetes mellitus by the end of the follow-up period and these effects were beyond glycemic control. Urinary beta2- and a1-microglobulin are significant biomarkers for incipient diabetic nephropathy and diabetic cerebral microangiopathy. These biomarkers showed that proximal tubule dysfunction may develop before the stage of microalbuminuria.
噻唑烷二酮类药物在各种水平上发挥着多效性作用，通过降低 2 型糖尿病患者的胰岛素抵抗来降低血糖。
评估罗格列酮与格列美脲对 2 型糖尿病患者的肾和神经保护作用。还评估了几种生物标志物在诊断早期糖尿病肾病和脑微血管病变中的相关性。
34 例 2 型糖尿病患者接受了为期 1 年的开放性随机对照试验。A 组包括 17 例患者（7 名男性，10 名女性，平均年龄 63 +/- 8.07 岁），接受罗格列酮联合二甲双胍治疗；B 组包括 17 例患者（7 名男性，10 名女性，平均年龄 63.2 +/- 7.19 岁），接受格列美脲联合二甲双胍治疗。所有患者在开始时、6 个月时和研究结束时评估血清和尿液β2-微球蛋白、尿α1-微球蛋白、血清胱抑素 C、血清肌酐、肾小球滤过率、C 反应蛋白、纤维蛋白原、糖化血红蛋白、胆固醇、甘油三酯、血红蛋白和尿白蛋白/肌酐比值（UACR）。还测量了脑血流动力学参数：颈内动脉和大脑中动脉的搏动指数和阻力指数，以及颈总动脉的内-中膜厚度。
在 1 年时，A 组和 B 组之间在血清胱抑素 C（P < 0.04）、尿β2-微球蛋白（P < 0.004）、尿α1-微球蛋白（P < 0.0001）、C 反应蛋白（P < 0.0001）、纤维蛋白原（P < 0.0001）、血清肌酐（P < 0.0024）、肾小球滤过率（P < 0.0010）、UACR（P < 0.0001）和脑血流动力学指标方面存在差异。α1-和β2-微球蛋白的增加先于微量白蛋白尿的发生。UACR 与尿α1-微球蛋白（r = 0.4854）、尿β2-微球蛋白（r = 0.4867）和血清胱抑素 C（r = 0.3702）相关。A 组的脑血管参数较 B 组改善，与尿β2-和α1-微球蛋白、C 反应蛋白、纤维蛋白原、肾小球滤过率和糖尿病病程相关。
罗格列酮在随访结束时显示出对 2 型糖尿病患者的肾和神经保护作用，其作用超出了血糖控制的范围。尿β2-和α1-微球蛋白是早期糖尿病肾病和糖尿病脑微血管病变的重要生物标志物。这些生物标志物表明，近端肾小管功能障碍可能在微量白蛋白尿阶段之前发生。
