Johnson Brian F, Nesto Richard W, Pfeifer Michael A, Slater William R, Vinik Aaron I, Chyun Deborah A, Law Gordon, Wackers Frans J Th, Young Lawrence H
Pfizer Research, Groton, Connecticut, USA.
Diabetes Care. 2004 Feb;27(2):448-54. doi: 10.2337/diacare.27.2.448.
The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy.
Diabetic subjects with neuropathy (n = 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year.
After 1 year of ARI treatment, there were increases in resting LVEF (P < 0.02), cardiac output (P < 0.03), LV stroke volume (P < 0.004), and exercise LVEF (P < 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P < 0.03), stroke volume (P < 0.02), and end diastolic volume (P < 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group.
Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.
本研究的目的是确定用醛糖还原酶抑制剂（ARI）治疗对患有神经病变的糖尿病患者无症状心脏异常是否有有益影响。
通过门控放射性核素心室造影确定患有神经病变（n = 81）且在最大量自行车运动期间舒张期峰值充盈率低或左心室（LV）射血分数（LVEF）增强受损的糖尿病受试者。通过临床评估、心肌灌注成像和超声心动图排除冠状动脉疾病、左心室肥厚和瓣膜性心脏病。受试者被随机分配接受盲法治疗，每日服用安慰剂或ARI唑泊司他500或1000 mg，为期1年。
ARI治疗1年后，静息LVEF（P < 0.02）、心输出量（P < 0.03）、左心室每搏输出量（P < 0.004）和运动LVEF（P < 0.001）均增加。在接受安慰剂治疗的受试者中，运动心输出量（P < 0.03）、每搏输出量（P < 0.02）和舒张末期容积（P < 0.04）均降低。运动LVEF随ARI治疗而增加，与血压、胰岛素使用或基线心率变异性异常的存在无关。两组静息舒张期充盈率均无变化。
患有神经病变的糖尿病患者存在左心室异常，ARI治疗可使其稳定并部分逆转。
