Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Diabetes Care. 2010 Jun;33(6):1344-6. doi: 10.2337/dc09-2340. Epub 2010 Mar 23.
Our aim was to examine the effect of cyclooxygenase 2 (COX2) inhibition on endothelial function in subjects with type 1 diabetes analyzed on the basis of renal filtration status.
Flow-mediated dilation (FMD) was determined in type 1 diabetic subjects and hyperfiltration (glomerular filtration rate >or=135 ml/min/1.73 m(2), n = 13) or normofiltration (glomerular filtration rate >or=135 ml/min/1.73 m(2), n = 11). Studies were performed before and after celecoxib (200 mg daily for 14 days) during euglycemia and hyperglycemia.
Baseline parameters were similar in the two groups. Pretreatment, FMD was augmented in normofiltering versus hyperfiltering subjects during clamped euglycemia (10.2 +/- 5.3% vs. 5.9 +/- 2.3%, P = 0.003). COX2 inhibition suppressed FMD in normofiltering (10.2 +/- 5.3% to 5.8 +/- 3.4%, P = 0.006) versus hyperfiltering subjects (ANOVA interaction, P = 0.003).
Systemic hemodynamic function, including the response to COX2 inhibition, is related to filtration status in diabetic subjects and may reflect general endothelial dysfunction.
本研究旨在探讨环氧化酶 2（COX2）抑制剂对 1 型糖尿病患者内皮功能的影响，并根据肾功能滤过状态进行分析。
在 1 型糖尿病患者中检测血流介导的扩张（FMD），并根据肾小球滤过率（GFR）分为高滤过组（GFR>or=135 ml/min/1.73 m2，n = 13）和正常滤过组（GFR>or=135 ml/min/1.73 m2，n = 11）。在正常血糖和高血糖状态下，分别于使用塞来昔布（200 mg/天，共 14 天）前后进行研究。
两组患者的基线参数相似。在夹闭正常血糖时，与高滤过组相比，正常滤过组的 FMD 明显增强（10.2 +/- 5.3% vs. 5.9 +/- 2.3%，P = 0.003）。COX2 抑制剂抑制了正常滤过组（10.2 +/- 5.3%到 5.8 +/- 3.4%，P = 0.006）和高滤过组（ANOVA 交互作用，P = 0.003）的 FMD。
包括 COX2 抑制剂反应在内的全身血液动力学功能与糖尿病患者的滤过状态有关，可能反映了普遍的内皮功能障碍。
