Hunter S J, Harper R, Ennis C N, Crothers E, Sheridan B, Johnston G D, Atkinson A B, Bell P M
Metabolic Unit, Royal Victoria Hospital, Belfast, UK.
J Hypertens. 1998 Jan;16(1):103-9. doi: 10.1097/00004872-199816010-00015.
To determine whether combination of an angiotensin converting enzyme inhibitor with a high dose of thiazide diuretic avoids adverse metabolic consequences of thiazide diuretics.
Double-blind randomized crossover study of two 12-week treatment periods with captopril (up to 100 mg/day) either alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period.
Outpatient clinics in greater Belfast.
Fifteen white non-diabetic essential hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast.
Systolic and diastolic blood pressures and peripheral and hepatic insulin action.
Two patients failed to complete the study. Blood pressure was lowered (139/89+/-18/7 mmHg combination versus 160/97+/-21/7 mmHg captopril; P < 0.001). Fasting insulin level was raised (7.9+/-3.6 mU/l combination versus 6.2+/-3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and triglyceride levels. Serum potassium level was lowered (3.8+/-0.4 mmol/l combination versus 4.2+/-0.4 mmol/l captopril, P < 0.05). Postabsorptive endogenous glucose production was raised (10.8+/-1.7 micromol/kg per min combination versus 10.0+/-1.5 micromol/kg per min captopril; P < 0.01) and was greater than baseline (9.7+/-2.1 micromol/kg per min, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to maintain euglycaemia did not differ (32.4+/-7.6 micromol/kg per min captopril, 32.7+/-6.2 micromol/kg per min combination, 31.5+/-7.2 micromol/kg per min baseline).
Combination therapy increased glucose production (compared with captopril alone), indicating hepatic insulin resistance. It cannot be assumed that combined preparations with angiotensin converting enzyme inhibitors will ameliorate adverse effects of high doses of thiazide diuretics on insulin action.
确定血管紧张素转换酶抑制剂与高剂量噻嗪类利尿剂联合使用是否可避免噻嗪类利尿剂的不良代谢后果。
双盲随机交叉研究，两个为期12周的治疗期，卡托普利（最高100毫克/天）单独使用或与5毫克苄氟噻嗪联合使用，在为期6周的安慰剂导入期后给药。治疗期之间有一个为期6周的安慰剂洗脱期。
大贝尔法斯特的门诊诊所。
从大贝尔法斯特的普通诊所招募了15名年龄小于65岁的白人非糖尿病原发性高血压患者（7名男性）。
收缩压和舒张压以及外周和肝脏胰岛素作用。
两名患者未完成研究。血压降低（联合用药组为139/89±18/7毫米汞柱，卡托普利组为160/97±21/7毫米汞柱；P<0.001）。空腹胰岛素水平升高（联合用药组为7.9±3.6毫单位/升，基线为6.2±3.2毫单位/升；P<0.001）。治疗组之间的血糖、尿酸、胆固醇和甘油三酯水平无差异。血清钾水平降低（联合用药组为3.8±0.4毫摩尔/升，卡托普利组为4.2±0.4毫摩尔/升，P<0.05）。吸收后内源性葡萄糖生成增加（联合用药组为10.8±1.7微摩尔/千克每分钟，卡托普利组为10.0±1.5微摩尔/千克每分钟；P<0.01），且高于基线水平（9.7±2.1微摩尔/千克每分钟，P<0.05）。两种治疗方法对胰岛素抑制葡萄糖生成的作用相似。维持血糖正常所需的外源性葡萄糖输注速率无差异（卡托普利组为32.4±7.6微摩尔/千克每分钟，联合用药组为32.7±6.2微摩尔/千克每分钟，基线为31.5±7.2微摩尔/千克每分钟）。
联合治疗增加了葡萄糖生成（与单独使用卡托普利相比），表明存在肝脏胰岛素抵抗。不能假定血管紧张素转换酶抑制剂联合制剂会改善高剂量噻嗪类利尿剂对胰岛素作用的不良影响。
