Hypertension：无糖尿病患者ACEI与小剂量噻嗪利尿剂联用对胰岛素作用影响不大

到目前为止关于降压治疗最大临床研究（Lipid-Lowering Treatment to Prevent Heart Attack Trial ，ALLHAT）发现利尿剂在降低某些心血管结局上优于其他降压药，但是与ACE抑制剂及钙离子拮抗剂相比，利尿剂增加新发2型糖尿病风险。来自北爱尔兰的研究人员McHenry CM等曾早些时候发现ACE抑制剂对胰岛素的作用是中性的。与单用ACE抑制相比，高剂量利尿剂（苄氟噻嗪 5mg）与ACE抑制联用会降低胰岛素的敏感性。对于合并或不合并糖尿病的原发性高血压患者，小剂量利尿剂（苄氟噻嗪 1.25mg 每日）与常规剂量（5mg 每日）可有效降压，且对代谢的影响较小。不过，他们还发现糖尿病患者中与单用ACE抑制相比，联用低剂量的利尿剂和ACE抑制剂与对胰岛素敏感性有不利影响。基于上述结果，他们进一步研究了在非糖尿病患者中，联用两种药物是否会对代谢有相似的影响。该研究为随机双盲交叉设计研究。
在研究中首先停掉患者所有降压药物并以安慰剂替代治疗6周，之后予以患者50mg （每日两次）卡托普利再加上苄氟噻嗪12.5mg（CB）或安慰剂（CP）治疗，服用12周以后再停用苄氟噻嗪或安慰剂。然后在6周的药物洗脱期间，继续服用卡托普利。接下来随机分配苄氟噻嗪或安慰剂治疗12周。分别在安慰剂替代治疗6周后以及两个12周的研究阶段结束时采用高胰岛素正葡萄糖钳夹技术测量胰岛素作用。两个治疗组间空腹血糖和胰岛素浓度无差异。维持各组血糖正常的葡萄糖输注速率为CP 22.1±2.2 和 CB 22.2±2.2 （单位：μmol/kg/min）。基础状态（CP 8.9±0.5比CB 9.5±0.7 μmol/kg/min; P=0.23）或高胰岛素血症时（CP 2.2±0.6比CB 1.5±0.3 μmol/kg/min；P=0.30） 的内源性葡萄糖生成无差异。
该研究发现与2型糖尿病患者不同，在无糖尿病的高血压患者中ACE抑制剂与小剂量噻嗪类利尿剂联用与ACE抑制剂单用相比并未对胰岛素的作用造成不利影响。
与高血压相关的拓展阅读：

• JAMA Neurol:高血压协同致AD病理蛋白沉积
• Hypertension：靶向交感神经消融可降低遗传盐敏感性高血压
• 摄钠过量，幼儿也患高血压
• Diabetologia:血钾低的高血压患者易患糖尿病
• Diabetes Care：糖尿病患者高血压越早治疗越好
• Hypertension：非吸烟者中血清可替宁水平与高血压相关 更多信息请点击：有关高血压更多资讯

Effects on insulin action of adding low-dose thiazide to Angiotensin-converting enzyme inhibitor in essential hypertension.
Abstract
Concern exists regarding adverse metabolic effects of antihypertensive agents. In the United States, diuretics are recommended first-line but additional agents, usually angiotensin-converting enzyme (ACE) inhibitors, are often required to meet blood pressure targets. We have previously shown that the combination of low-dose diuretic with an ACE inhibitor has detrimental effects on insulin action compared with ACE inhibitor alone in hypertensive type 2 diabetic patients. Our aim was to establish whether similar effects occur in nondiabetic hypertensive patients using this combination. A randomized double-blind placebo-controlled crossover design was used. After a 6-week run-in, when regular antihypertensive medications were withdrawn and placebo substituted, patients received captopril 50 mg twice daily with either bendroflumethiazide 1.25 mg (CB) or placebo (CP) for 12 weeks with a 6-week wash-out between treatments. Insulin action was assessed by hyperinsulinemic euglycemic clamp after the 6-week run-in and at the end of each treatment period. There were no differences between treatments in fasting glucose or insulin concentrations. Glucose infusion rates required to maintain euglycemia were the same with each treatment (CP 22.1±2.2 vs CB 22.2±2.2 μmol/kg per minute). There was no difference in endogenous glucose production in the basal state (CP 8.9±0.5 vs CB 9.5±0.7 μmol/kg per minute; P=0.23) or during hyperinsulinemia (CP 2.2±0.6 vs CB 1.5±0.3 μmol/kg per minute; P=0.30). In contrast to the situation in type 2 diabetes mellitus, ACE inhibitor combined with low-dose thiazide diuretic does not adversely affect insulin action when compared with ACE inhibitor alone in nondiabetic hypertensive patients.