Holman Rury R, Paul Sanjoy K, Bethel M Angelyn, Matthews David R, Neil H Andrew W
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom.
N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.
During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes.
Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories.
Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002).
Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.)
在英国前瞻性糖尿病研究（UKPDS）中，接受强化血糖治疗的2型糖尿病患者发生微血管并发症的风险低于接受传统饮食治疗的患者。我们进行了试验后监测，以确定这种改善的血糖控制是否持续存在，以及这种治疗对大血管结局是否有长期影响。
在5102例新诊断的2型糖尿病患者中，4209例被随机分配接受传统治疗（饮食限制）或强化治疗（磺脲类药物或胰岛素，或超重患者使用二甲双胍）以控制血糖。在试验后监测中，3277例患者被要求每年到UKPDS诊所就诊5年，但未尝试维持他们之前分配的治疗。年度问卷用于随访无法到诊所就诊的患者，6至10年的所有患者通过问卷进行评估。我们根据之前的随机分组类别，在意向性分析的基础上检查了UKPDS预先设定的七个总体临床结局。
糖化血红蛋白水平的组间差异在第一年之后消失。在磺脲类药物-胰岛素组中，任何糖尿病相关终点（9%，P=0.04）和微血管疾病（24%，P=0.001）的风险相对降低在10年时持续存在，随着更多事件的发生，心肌梗死（15%，P=0.01）和任何原因导致的死亡（13%，P=0.007）的风险降低也逐渐显现。在二甲双胍组中，任何糖尿病相关终点（21%，P=0.01）、心肌梗死（33%，P=0.005）和任何原因导致的死亡（27%，P=0.002）的风险显著降低持续存在。
尽管血糖差异在早期消失，但在试验后10年的随访中观察到微血管风险持续降低，以及心肌梗死和任何原因导致的死亡的风险逐渐降低。二甲双胍治疗后的持续获益在超重患者中明显。（UKPDS 80；当前对照试验编号，ISRCTN75451837）
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