THE EFFECT OF INTENSIVE TREATMENT OF DIABETES ON THE DEVELOPMENT AND PROGRESSION OF LONG-TERM COMPLICATIONS IN INSULIN-DEPENDENT DIABETES-MELLITUS
THE EFFECT OF INTENSIVE TREATMENT OF DIABETES ON THE DEVELOPMENT AND PROGRESSION OF LONG-TERM COMPLICATIONS IN INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI：
10.1056/nejm199307293290502
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发表时间：
1993-09-30
影响因子：
158.5
通讯作者：
SIEBERT, C
中科院分区：
文献类型：
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作者：
SHAMOON, H;DUFFY, H;SIEBERT, C
背景胰岛素依赖型糖尿病患者血糖浓度和微血管并发症之间的因果关系尚未建立。我们将102例胰岛素依赖型糖尿病、非增殖性视网膜病变、血清肌酐浓度正常和血糖控制不满意的患者随机分为强化胰岛素治疗组（48例）和标准胰岛素治疗组（54例）。然后我们在18个月、3年、5年和7.5年后评估他们的微血管并发症。强化治疗组的平均（+/-SD）糖化血红蛋白值从9.5+/-1.3%降至7.1+/-0.7%，标准治疗组从9.4+/-1.4%降至8.5+/-0.7%（P = 0.001）。在接受强化治疗的12名患者（占分析中的27%）和接受标准治疗的27名患者（52%）中，发生了需要光凝的严重视网膜病变（P = 0.01）。6例接受强化治疗的患者（14%）和18例接受标准治疗的患者（35%）视力下降（P = 0.02）。强化治疗组有1例患者发生肾病（尿白蛋白排泄>200 μ g/min），而标准治疗组有9例患者发生肾病（P = 0.01）。强化治疗组中没有患者发生肾小球滤过率低于正常的肾病，而标准治疗组中有6例患者（P = 0.02）。标准治疗组中尺神经、胫神经、腓神经和腓肠神经的传导速度比强化治疗组明显降低。与标准治疗组相比，强化治疗组严重视网膜病变的比值比为0.4（95%置信区间，0.2 - 1.0; P = 0.04）。肾病的相应比值比为0.1（95%可信区间，0 ~ 0.8; P = 0.04）。与标准治疗相比，长期强化胰岛素治疗可延缓胰岛素依赖型糖尿病患者微血管并发症的发生。长期的微血管和神经系统并发症导致胰岛素依赖型糖尿病（IDDM）患者的主要发病率和死亡率。我们研究了以维持血糖浓度接近正常范围为目标的强化治疗是否可以降低这些并发症的频率和严重程度。共有1441例基线时无视网膜病变的IDDM - 726患者（一级预防队列）和715例轻度视网膜病变患者（二级干预队列）被随机分配到强化治疗组，接受外部胰岛素泵或每日3次或更多次胰岛素注射，并在频繁血糖监测的指导下进行治疗，或接受每日1次或2次胰岛素注射的常规治疗。患者平均随访6.5年，定期评估视网膜病变和其他并发症的外观和进展。在一级预防队列中，与常规治疗相比，强化治疗使视网膜病变发生的校正平均风险降低了76%（95%置信区间为62%至85%）。在二次干预队列中，强化治疗使视网膜病变的进展减缓了54%（95%置信区间，39%至66%），并使增殖性或严重非增殖性视网膜病变的发展减少了47%（95%置信区间，14%至67%）。在两个队列中，强化治疗减少了微量白蛋白尿的发生（每24小时尿白蛋白排泄大于或等于40 mg）减少39%（95%置信区间，21%至52%），（每24小时尿白蛋白排泄量大于或等于300 mg）减少54%（95%置信区间，19%至74%），临床神经病变的60%（95%置信区间，38%至74%）。与强化治疗相关的主要不良事件是严重低血糖增加2 - 3倍。强化治疗可有效延迟IDDM患者的糖尿病视网膜病变、肾病和神经病变的发作并减缓其进展。
Background. A cause-and-effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established.Methods. We randomly assigned 102 patients with insulin-dependent diabetes' mellitus, nonproliferative retinopathy, normal serum creatinine concentrations, and unsatisfactory blood glucose control to intensified insulin treatment (48 patients) or standard insulin treatment (54 patients). We then evaluated them for microvascular complications after 18 months and 3, 5, and 7.5 years.Results. Mean (+/-SD) glycosylated hemoglobin values were reduced from 9.5+/-1.3 percent to 7.1+/-0.7 percent in the group receiving intensified treatment and from 9.4+/-1.4 percent to 8.5+/-0.7 percent in the group receiving standard treatment (P = 0.001). In 12 of the patients receiving intensified treatment (27 percent of those included in the analysis) and 27 of those receiving standard treatment (52 percent), serious retinopathy requiring photocoagulation developed (P = 0.01). Visual acuity decreased in 6 patients receiving intensified treatment (14 percent) and in 18 receiving standard treatment (35 percent) (P = 0.02). Nephropathy (urinary albumin excretion, >200 mug per minute) developed in one patient in the group receiving intensified treatment, as compared with nine patients in the group receiving standard treatment (P = 0.01). No patient in the intensified-treatment group had nephropathy with subnormal glomerular filtration rates, as compared with six patients in the standard-treatment group (P = 0.02). The conduction velocities of the ulnar, tibial, peroneal, and sural nerves decreased significantly more in the standard-treatment group than in the intensified-treatment group. The odds ratio for serious retinopathy was 0.4 (95 percent confidence interval, 0.2 to 1.0; P = 0.04) in the intensified-treatment group as compared with the standard-treatment group. The corresponding odds ratio for nephropathy was 0.1 (95 percent confidence interval, 0 to 0.8; P = 0.04).Conclusions. Long-term intensified insulin treatment, as compared with standard treatment, retards the development of microvascular complications in patients with insulin-dependent diabetes mellitus.Background. Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.Methods. A total of 1441 patients with IDDM - 726 with no retinopathy at base line (the primary-prevention cohort) and 715 with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. The patients were followed for a mean of 6.5 years, and the appearance and progression of retinopathy and other complications were assessed regularly.Results. In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy. In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent (95 percent confidence interval, 39 to 66 percent) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent (95 percent confidence interval, 14 to 67 percent). In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of greater-than-or-equal-to 40 mg per 24 hours) by 39 percent (95 percent confidence interval, 21 to 52 percent), that of albuminuria (urinary albumin excretion of greater-than-or-equal-to 300 mg per 24 hours) by 54 percent (95 percent confidence interval, 19 to 74 percent), and that of clinical neuropathy by 60 percent (95 percent confidence interval, 38 to 74 percent). The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.Conclusions. Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.