Ebbehøj E, Poulsen P L, Hansen K W, Knudsen S T, Mølgaard H, Mogensen C E
Medical Department M, Diabetes and Endocrinology, Kommunehospitalet, Aarhus University Hospital, Denmark.
Diabetologia. 2002 Jul;45(7):965-75. doi: 10.1007/s00125-002-0869-7. Epub 2002 Jun 6.
AIMS/HYPOTHESIS: Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In non-diabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that beta-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional beta-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria.
We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out.
Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in daytime diastolic blood pressure was shown, no alterations in diurnal variation of blood pressure or urine albumin excretion were observed.
CONCLUSION/INTERPRETATION: These preliminary findings indicate that beta-blocker treatment could improve autonomic function in Type I diabetic patients with abnormal albuminuria and an associated high risk of cardiovascular disease.
目的/假设：糖尿病肾病与包括猝死在内的心脏死亡高风险相关。这可能与交感神经和副交感神经张力失衡导致心率变异性（HRV）降低有关。在非糖尿病患者中，HRV降低是心血管死亡的有力预测指标。对非糖尿病患者的研究表明，β受体阻滞剂可改善已知反映副交感神经功能的HRV参数。我们研究的目的是调查在接受血管紧张素转换酶抑制剂治疗且存在蛋白尿异常的Ⅰ型（胰岛素依赖型）糖尿病患者中，额外使用β受体阻滞剂治疗对心脏自主神经功能、血压和尿白蛋白排泄的影响。
我们对20名参与随机、安慰剂对照、双盲、交叉试验的患者进行了为期6周的美托洛尔（100 mg，每日一次，零级动力学制剂）治疗效果研究。在动态条件下，通过24小时动态心电图监测、24小时动态血压记录和24小时分段尿液收集对患者进行同步监测。通过四种不同方法评估心率变异性；动态HRV分析通过频谱和时域分析进行，在研究日进行短期频谱分析和床边测试。
通过短期频谱分析评估，美托洛尔治疗改善了迷走神经张力。24小时动态HRV分析显示，一些反映迷走神经功能的参数有所改善。白天舒张压略有下降，未观察到血压昼夜变化或尿白蛋白排泄的改变。
结论/解读：这些初步研究结果表明，β受体阻滞剂治疗可改善存在蛋白尿异常且心血管疾病风险较高的Ⅰ型糖尿病患者的自主神经功能。
