Abraira Carlos, Duckworth William, McCarren Madeline, Emanuele Nicholas, Arca Danielle, Reda Domenic, Henderson William
VA Medical Center, Miami, FL 33125, USA.
J Diabetes Complications. 2003 Nov-Dec;17(6):314-22. doi: 10.1016/s1056-8727(02)00277-5.
Long-term glycemic control trials in type 2 diabetes show as the main clinical benefit a difference in retinal photocoagulation (3/1000 in the UK Prospective Diabetes Study [UKPDS]), but no effect on visual acuity or renal failure. No intensive glycemic control trial has yet affected cardiovascular (CV) events, the main cause of morbidity and mortality. By contrast, modest blood pressure reduction has protective effects on visual acuity, renal function, CV events, and mortality. Optimal glycemic control goals are not established in elderly, obese persons with advanced complications, the most common patients in the Veterans Affairs (VA) system. The earlier feasibility trial in such patients (VA-CSDM) suggested potentially worse CV outcomes with lower attained hemoglobin A1c (HbA1c) levels.
The primary objective of the Veterans Affairs Diabetes Trial (VADT) is the assessment of the effect of intensive glycemic treatment on CV events. Other objectives are effects on microangiopathy, quality of life, and cost effectiveness.
The VADT, started in December 2000, is enrolling 1700 men and women previously uncontrolled on insulin or maximum doses of oral agents at 20 VA medical centers. Accrual is 2 years and follow-up is 5-7 years, with visits every 1.5 months. The study has a power of 86% to detect a 21% relative reduction in major CV events (CV death, myocardial infarction [MI], cerebrovascular accident [CVA], congestive heart failure [CHF], revascularization and amputation for ischemia). Subjects are randomized to an intensive arm aiming at normal HbA1c levels or to a standard arm with usual, improved glycemic control. An HbA1c separation of >1.5% is to be maintained (expected 2%). Both arms receive step therapy: glimepiride or metformin plus rosiglitazone and addition of insulin or other oral agents to achieve goals. Strict control of blood pressure and dyslipidemia, daily aspirin, diet, and education are identical in both arms. Plasma fibrinogen, plasminogen-activating inhibitor I (PAI-I), lipids, renal function parameters, and ECG are measured throughout. Stereo retinal photographs are obtained at entry and 5 years, eye examinations yearly, and intervention as needed to prevent visual deterioration. Recruitment is proceeding on schedule: the current mean HbA1c at entry is 9.4+/-1.6% and mean duration of diagnosed diabetes 11+/-8 years.
2型糖尿病长期血糖控制试验显示，主要临床益处是视网膜光凝治疗方面存在差异（英国前瞻性糖尿病研究[UKPDS]中为3/1000），但对视力或肾衰竭无影响。尚无强化血糖控制试验对心血管（CV）事件产生影响，而CV事件是发病和死亡的主要原因。相比之下，适度降低血压对视力、肾功能、CV事件及死亡率具有保护作用。在老年、肥胖且有晚期并发症的患者（退伍军人事务部[VA]系统中最常见的患者类型）中，尚未确立最佳血糖控制目标。此前针对此类患者的可行性试验（VA-CSDM）表明，血红蛋白A1c（HbA1c）水平降低可能会导致更差的CV结局。
退伍军人事务部糖尿病试验（VADT）的主要目的是评估强化血糖治疗对CV事件的影响。其他目的包括对微血管病变、生活质量及成本效益的影响。
VADT于2000年12月启动，在20个VA医疗中心招募1700名之前使用胰岛素或最大剂量口服药物治疗但血糖未得到控制的男性和女性。入组为期2年，随访5 - 7年，每1.5个月进行一次访视。该研究有86%的把握度检测到主要CV事件（CV死亡、心肌梗死[MI]、脑血管意外[CVA]、充血性心力衰竭[CHF]、血运重建及缺血性截肢）相对减少21%。受试者被随机分为旨在使HbA1c水平正常化的强化治疗组或血糖控制达到常规改善水平的标准治疗组。HbA1c差值要维持在>1.5%（预期为2%）。两组均接受阶梯治疗：格列美脲或二甲双胍加罗格列酮，并加用胰岛素或其他口服药物以实现目标。两组在血压和血脂异常的严格控制、每日服用阿司匹林、饮食及教育方面均相同。全程测量血浆纤维蛋白原、纤溶酶原激活物抑制剂I（PAI-I）、血脂、肾功能参数及心电图。在入组时和5年时拍摄立体视网膜照片，每年进行眼科检查，并根据需要进行干预以防止视力恶化。招募工作按计划进行：目前入组时的平均HbA1c为9.4±1.6%，确诊糖尿病的平均病程为11±8年。
