N Engl J Med. 2011 Dec 22;365(25):2366-76. doi: 10.1056/NEJMoa1111732. Epub 2011 Nov 12.
An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.
In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits.
Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates.
The long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.).
肾小球滤过率（GFR）受损会导致终末期肾病，并增加心血管疾病和死亡的风险。1 型糖尿病患者患肾脏疾病的风险很高，但目前尚无干预措施被证明可预防该人群的 GFR 受损。
在糖尿病控制和并发症试验（DCCT）中，1441 名 1 型糖尿病患者被随机分配接受 6.5 年的强化糖尿病治疗，以达到接近正常的葡萄糖浓度，或接受常规糖尿病治疗，以预防高血糖症状。随后，在观察性糖尿病干预和并发症流行病学（EDIC）研究中对 1375 名参与者进行了随访。在两项研究的整个过程中，每年测量一次血清肌酐水平。使用慢性肾脏病流行病学合作公式估计 GFR。我们分析了两项研究的数据，以确定强化糖尿病治疗对 GFR 受损风险的长期影响，GFR 受损定义为两次连续研究访问时估计的 GFR 低于每分钟每 1.73 m(2) 体表面积 60 ml。
在两项研究的中位随访期为 22 年期间，接受强化治疗的 24 名参与者和接受常规治疗的 46 名参与者发生 GFR 受损（强化治疗风险降低 50%；95%置信区间，18 至 69；P=0.006）。在这些参与者中，强化治疗组有 8 名患者发展为终末期肾病，常规治疗组有 16 名患者发展为终末期肾病。与常规治疗相比，强化治疗在 DCCT 研究期间导致估计的 GFR 平均每分钟下降 1.7 ml/1.73 m(2)，但在 EDIC 研究期间，GFR 下降速度较慢，估计的 GFR 平均每分钟增加 2.5 ml/1.73 m(2)（两次比较均 P<0.001）。在调整糖化血红蛋白水平或白蛋白排泄率后，强化治疗对 GFR 受损风险的有益影响完全减弱。
在 1 型糖尿病早期接受强化糖尿病治疗的患者中，GFR 受损的长期风险明显低于接受常规糖尿病治疗的患者。（由美国国立糖尿病、消化和肾脏疾病研究所等资助；DCCT/EDIC 临床试验.gov 编号，NCT00360815 和 NCT00360893）。
