Beulens J W J, Patel A, Vingerling J R, Cruickshank J K, Hughes A D, Stanton A, Lu J, McG Thom S A, Grobbee D E, Stolk R P
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, GA, the Netherlands.
Diabetologia. 2009 Oct;52(10):2027-36. doi: 10.1007/s00125-009-1457-x. Epub 2009 Jul 25.
AIMS/HYPOTHESIS: The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients.
The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2 x 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril-indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA(1c) of < or = 6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of > or =2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome.
Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n = 623) experienced incidence or progression of retinopathy compared with patients on placebo (n = 618), but the difference was not significant (OR 0.78; 95% CI 0.57-1.06; p = 0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29-0.88; p = 0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38-0.94; p = 0.025). Compared with standard glucose control (n = 611), intensive glucose control (n = 630) did not reduce (p = 0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61-1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere.
CONCLUSIONS/INTERPRETATION: Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions.
ClinicalTrials.gov ID no. NCT00145925.
Grants from Servier and the National Health and Medical Research Council of Australia.
目的/假设：本研究旨在探讨血压降低和强化血糖控制对2型糖尿病患者视网膜病变发生率及进展的影响。
糖尿病和血管疾病行动：培哚普利吲达帕胺与美吡达（亚莫利）对照评估（ADVANCE）视网膜测量研究，是ADVANCE研究的一项子研究，这是一项随机（采用基于计算机的中心程序）对照的2×2析因试验，包括培哚普利吲达帕胺与安慰剂降低血压的双盲比较，以及标准血糖控制与强化血糖控制的开放比较，目标是使来自ADVANCE中心的1602例有眼底照相机的糖尿病患者的糖化血红蛋白（HbA1c）≤6.5%。在2001年至2008年期间进行。在基线和最后一次访视时，拍摄七视野立体视网膜照片并由盲法阅片者分级（来自1241例患者的可分级基线和最终照片）。糖尿病视网膜病变早期治疗研究分类中进展≥2级（使用分级最差的眼）是主要结局。
在4.1年期间，59例（4.8%）患者视网膜病变进展，128例（10.3%）患者出现视网膜病变。与接受安慰剂治疗的患者（n = 618）相比，接受降压治疗的患者（n = 623）发生视网膜病变的发生率或进展较少，但差异无统计学意义（比值比0.78；95%置信区间0.57 - 1.06；p = 0.12）。与安慰剂相比，降压治疗减少了黄斑水肿的发生（比值比0.50；95%置信区间0.29 - 0.88；p = 0.016）以及动静脉交叉征（比值比0.60；95%置信区间0.38 - 0.94；p = 0.025）。与标准血糖控制（n = 611）相比，强化血糖控制（n = 630）并未降低（p = 0.27）视网膜病变的发生率及进展（比值比0.84；95%置信区间0.61 - 1.15）。在调整基线视网膜出血后，强化血糖控制观察到微动脉瘤、硬性渗出和黄斑水肿的风险降低，但接近显著水平。两种治疗的这些效果是独立且相加且相加的。ADVANCE研究中的不良事件在其他地方报道。
结论/解读：尽管观察到一致的获益趋势，且两种干预措施均使一些病变显著减少，但血压降低或强化血糖控制并未显著降低视网膜病变的发生率及进展。
ClinicalTrials.gov标识符：NCT00145925。
施维雅公司和澳大利亚国家卫生与医学研究委员会提供的资助。
