Azad N, Emanuele N V, Abraira C, Henderson W G, Colwell J, Levin S R, Nuttall F Q, Comstock J P, Sawin C T, Silbert C, Rubino F A
Hines VA Hospital, Hines, IL, USA.
J Diabetes Complications. 1999 Sep-Dec;13(5-6):307-13. doi: 10.1016/s1056-8727(99)00062-8.
To determine whether a difference in HbA(1c) could be safely sustained between a standard therapy (STD) arm and an intensive therapy (INT) arm, while maintaining HbA(1c) levels in both arms within a range acceptable in community practice. The effects of intensive treatment on various parameters were studied in this feasibility trial. We report here the results of 24 months of INT on peripheral and autonomic neuropathy.A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: (1) an evening insulin injection, (2) the same injection adding daytime glipizide, (3) two injections of insulin alone, and (4) multiple daily injections. Peripheral neuropathy was diagnosed clinically by a history and physical examination, and by abnormal autonomic neuropathy Valsalva ratio (VR < 1.2) and RR variation (RRV < 10). An average HbA(1c) separation of 2.07% was achieved with INT, having HbA(1c) at or below 7.3% (p = 0. 001 versus STD). Baseline prevalence of peripheral neuropathy was 53% in STD, and 48% in INT. By 24 months, the prevalence increased to 69% in STD (p = 0.005 versus baseline), and to 64% in INT (p = 0. 008 versus baseline, but no different than STD). Though INT did not reverse all elements of peripheral neuropathy, there was a decreased prevalence of cranial neuropathy (p = 0.053 versus STD) and more frequent preservation of touch sensation in the upper extremities (p = 0.03 versus STD) in INT. At baseline, an abnormal Valsalva ratio and/or RR variation was seen in 38% of STD and 31% of INT. By 24 months in STD, the prevalence rose to 55% (p = 0.0067 versus baseline), and in INT, to 48% (p = 0.012 versus baseline and no different from STD). The prevalence of erectile dysfunction increased from 53% at baseline to 73% at 2 years, p = 0.002 in STD, and from 51% to 73% at 2 years (p = 0.003 versus baseline) and no different from STD. There was no change in the frequency of abnormal gastrointestinal or sweating symptoms. Our conclusion was that 2 years of meticulous glycemic control did not decrease overall prevalence of peripheral or autonomic neuropathy. In fact, the prevalence rose equivalently and significantly in both treatment arms. There was some benefit, however, in decreased frequency of cranial neuropathy and better preservation of touch sensation in INT.
为确定在标准治疗（STD）组和强化治疗（INT）组之间，HbA(1c)的差异能否安全维持，同时使两组的HbA(1c)水平保持在社区医疗实践可接受的范围内。在这项可行性试验中研究了强化治疗对各种参数的影响。我们在此报告24个月强化治疗对外周神经病变和自主神经病变的结果。
一项前瞻性试验在五个医疗中心对153名60±6岁的男性进行，他们已知患有糖尿病7.8±4年。他们被随机分配到标准胰岛素治疗组（每日一次晨起注射）或强化治疗组，强化治疗组旨在实现血糖接近正常，并使糖化血红蛋白与标准组有临床显著差异。强化治疗组采用四步方案并每日进行血糖自我监测：（1）晚间胰岛素注射，（2）在同一注射中添加日间格列吡嗪，（3）单独两次胰岛素注射，（4）每日多次注射。外周神经病变通过病史、体格检查以及异常的自主神经病变瓦尔萨尔瓦比率（VR<1.2）和RR变异（RRV<10）进行临床诊断。强化治疗实现了HbA(1c)平均差异2.07%，强化治疗组的HbA(1c)处于或低于7.3%（与STD相比，p = 0.001）。外周神经病变的基线患病率在STD组为53%，在INT组为48%。到24个月时，STD组患病率增至69%（与基线相比，p = 0.005），INT组增至64%（与基线相比，p = 0.008，但与STD组无差异）。尽管强化治疗并未逆转外周神经病变的所有方面，但强化治疗组的颅神经病变患病率降低（与STD相比，p = 0.053）且上肢触觉保留更频繁（与STD相比，p = 0.03）。基线时，38%的STD组和31%的INT组出现异常的瓦尔萨尔瓦比率和/或RR变异。到24个月时，STD组患病率升至55%（与基线相比，p = 0.0067），INT组升至48%（与基线相比，p = 0.012，与STD组无差异）。勃起功能障碍的患病率从基线时的53%增至2年时的73%，在STD组p = 0.002，在INT组从51%增至2年时的73%（与基线相比，p = 0.003，与STD组无差异）。胃肠道或出汗异常症状的频率无变化。我们的结论是，2年的严格血糖控制并未降低外周或自主神经病变的总体患病率。事实上，两个治疗组的患病率均同等显著上升。然而，强化治疗组在降低颅神经病变频率和更好地保留触觉方面有一些益处。
