Nielsen S, Hove K Y, Dollerup J, Poulsen P L, Christiansen J S, Schmitz O, Mogensen C E
Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Aarhus, Denmark.
Diabetes Obes Metab. 2001 Dec;3(6):463-71. doi: 10.1046/j.1463-1326.2001.00169.x.
The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design.
Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 +/- 7 years (mean +/- s.d.), HbA1c 8.1 +/- 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo.
Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 +/- 11/8 vs. 130/76 +/- 12/6 mmHg, p < 0.05). A significant decline in GFR (133 +/- 23 vs. 140 +/- 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 +/- 3.5 vs. 26.2 +/- 3.6%, p < 0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 +/- 0.53 vs. 2.98 +/- 0.93 mg/kg/min) and insulin-stimulated states (6.84 +/- 2.52 vs. 6.97 +/- 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 +/- 0.34 vs. 1.33 +/- 0.18, mg/kg/min, p < 0.01) and during insulin stimulation (2.89 +/- 0.75 vs. 2.40 +/- 0.62 mg/kg/min, p < 0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups.
Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients.
采用双盲、安慰剂对照、交叉设计，在血压正常、尿白蛋白正常的1型糖尿病患者中研究血管紧张素II受体拮抗剂氯沙坦对肾脏血流动力学及胰岛素介导的葡萄糖处置的影响。
测量患者日间血压、肾小球滤过率（GFR，使用[125I] - 碘肽酸盐测定）、肾血浆流量（RPF，使用[131I] - 马尿酸测定）及尿白蛋白排泄率（UAE）。在9例患者（年龄30±7岁（均值±标准差），糖化血红蛋白8.1±1.1%）中，给予50mg/日氯沙坦或安慰剂治疗6周后，进行高胰岛素 - 正常血糖钳夹试验并间接测热。
与安慰剂相比，氯沙坦治疗后日间血压显著降低（122/70±11/8 vs. 130/76±12/6 mmHg，p<0.05）。氯沙坦组与安慰剂组相比，GFR显著下降（133±23 vs. 140±22 ml/分钟，p<0.05），滤过分数（FF；GFR/RPF）也显著下降（24.6±3.5 vs. 26.2±3.6%，p<0.05）。RPF和UAE未改变。在基础状态（2.61±0.53 vs. 2.98±0.93 mg/kg/分钟）和胰岛素刺激状态下（6.84±2.52 vs. 6.97±3.11 mg/kg/分钟），氯沙坦和安慰剂治疗后的同位素测定葡萄糖处置率相似。然而，在基础状态下（1.72±0.34 vs. 1.33±0.18，mg/kg/分钟，p<0.01）及胰岛素刺激期间（2.89±0.75 vs. 2.40±0.62 mg/kg/分钟，p<0.03），氯沙坦治疗后的葡萄糖氧化率较安慰剂组显著升高。氯沙坦治疗后基础状态及胰岛素刺激下的非氧化葡萄糖处置有下降趋势，但无统计学意义。治疗后内源性葡萄糖生成及脂质氧化未改变，在高胰岛素血症期间同样受到抑制。氯沙坦组和安慰剂组的血糖控制、总胆固醇、高密度脂蛋白（HDL）胆固醇及甘油三酯均保持稳定。
氯沙坦可降低血压、肾小球高滤过及FF，并改善血压正常、尿白蛋白正常的1型糖尿病患者基础状态及胰岛素刺激下的葡萄糖氧化。
