Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy
Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy
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DOI：
10.1152/ajprenal.00289.2005
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发表时间：
2006-03-01
影响因子：
4.2
通讯作者：
Agarwal, R
中科院分区：
文献类型：
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作者：
Agarwal, R
糖尿病肾病患者的心血管事件发生率和死亡率较高。非传统的心血管危险因素，如氧化应激和炎症被认为是特别重要的介导这些事件。研究表明，噻唑烷二酮类药物（TZDs）可以降低糖尿病患者或非糖尿病患者的非传统心血管风险水平。这种益处是否发生在糖尿病肾病患者中尚不清楚。我假设TZD吡格列酮与格列吡嗪相比可减轻显性糖尿病肾病患者的氧化应激和炎症。了氧化应激标志在来自参与一项随机、开放标签、盲法终点研究的显性糖尿病肾病患者的冷冻样本中，测量了血浆和尿白蛋白羰基和总蛋白羰基以及丙二醛、炎症[白色血细胞（WBC）计数、C-反应蛋白（CRP）、血浆IL-6、TNF-α]和斑块稳定性[基质金属蛋白酶9（MMP-9）]，格列吡嗪（n = 22）或吡格列酮（n = 22）的16周试验。吡格列酮治疗晚期糖尿病肾病男性患者使WBC计数降低1，125/mu 1（P < 0.001），CRP降低41%（P = 0.042），IL-6降低38%（P = 0.009），MMP-9降低29%（P = 0.016）。与格列吡嗪相比，吡格列酮组WBC计数特异性差异减少1，251/mu 1（P = 0.009），IL-6减少58%（P = 0.001）。两种降糖药均未观察到血浆TNF-α浓度或氧化应激标志物发生统计学显著变化。总之，吡格列酮降低了显性糖尿病肾病患者的促炎标志物，这表明对总体心血管风险具有潜在的有益作用。这一替代终点需要在旨在证明心血管保护作用的试验中得到证实。
Patients with diabetic nephropathy have a high rate of cardiovascular events and mortality. Nontraditional cardiovascular risk factors such as oxidative stress and inflammation are thought to be particularly important in mediating these events. Studies suggest that thiazolidinediones (TZDs) can reduce the level of nontraditional cardiovascular risk in people with or without diabetes mellitus. Whether this benefit occurs in patients with diabetic nephropathy is unknown. I hypothesized that the TZD pioglitazone will mitigate oxidative stress and inflammation compared with glipizide in patients with overt diabetic nephropathy. Markers of oxidative stress ( plasma and urine albumin carbonyl and total protein carbonyls and malondialdehyde), inflammation [ white blood cell (WBC) count, C-reactive protein (CRP), plasma IL-6, TNF-alpha], and plaque stability [matrix metalloproteinase 9 (MMP-9)] were measured in frozen samples obtained from patients with overt diabetic nephropathy participating in a randomized, open-label, blinded end-point, 16-wk trial with glipizide (n = 22) or pioglitazone (n = 22). Pioglitazone therapy in men with advanced diabetic nephropathy reduced WBC count by 1,125/mu 1 (P < 0.001), CRP by 41% (P = 0.042), IL-6 by 38% (P = 0.009), and MMP-9 by 29% (P = 0.016). Specific differential reductions in WBC count of 1,251/mu 1 (P = 0.009) and reduction in IL-6 of 58% with pioglitazone (P = 0.001) were seen compared with glipizide. There were no statistically significant changes observed with plasma TNF-alpha concentrations or markers of oxidative stress with either hypoglycemic agent. In conclusion, pioglitazone reduces proinflammatory markers in patients with overt diabetic nephropathy, which indicates potentially beneficial effects on overall cardiovascular risk. This surrogate end point needs to be confirmed in trials designed to demonstrate cardiovascular protection.