New J P, Bilous R W, Walker M
Department of Medicine, University of Newcastle upon Tyne, UK.
Diabet Med. 2000 Feb;17(2):134-40. doi: 10.1046/j.1464-5491.2000.00235.x.
The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus.
Insulin sensitivity was assessed after an acute dose (day 3) and 19 days continuous treatment (days 3-21) using the isoglycaemic, hyperinsulinaemic glucose clamp with D[3-3H] labelled glucose, a variable D[3-3H] priming dose and a 'hot' glucose infusion. Rates of glucose appearance (Ra) and glucose disappearance (Rd) were isotopically determined during the basal and insulin stimulated periods of the clamp. Twenty-four (5 female) hypertensive (blood pressure >75th centile for age and sex) patients with Type 2 diabetes mellitus were studied. Patients were randomized, in a double-blind manner, to either trandolapril 4 mg daily (T) or placebo (P).
Baseline (day 1) systolic (mean +/- SD; P 164+/-14 and T 168+/-13 mm Hg) and diastolic (P 93+/-6, and T 98+/-10 mm Hg) blood pressures were comparable. On days 3 and 21, significant reductions were observed in both groups (P<0.001). In the trandolapril-treated group, serum trandolapril concentrations were >200 pg/ml on days 3 and 21, in all patients apart from one subject at a single visit, while trandolapril was undetectable in the placebo group. Body mass index (BMI) was greater in T compared with P (32.2+/-5.4 v. 28.3+/-4.6, P = 0.07). After correcting for BMI, basal hepatic glucose output (HGO) P 2.6 (95% CI 2.23-3.13) and T 1.91 (1.33-2.51) mg x kg(-1) x min(-1) and clamped HGO P 0.32 (-0.44-1.09) and T 0.87 (0.40-1.34) mg x kg(-1) x min(-1) were similar in both groups. The insulin sensitivity index was comparable in both groups on all days. Total cholesterol concentrations were similar in both groups throughout the study. Triglyceride concentrations were significantly lower in group P 1.38 (1.07-1.68); T 2.14 (1.70-2.58) mmol/l, P<0.01), no significant treatment effect being observed.
An acute dose and 19 days' continuous treatment with trandolapril resulted in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension. These data support the metabolic neutrality of trandolapril in patients with Type 2 diabetes mellitus and hypertension.
本研究旨在探讨具有高组织摄取率的长效血管紧张素转换酶（ACE）抑制剂群多普利对2型糖尿病高血压患者胰岛素敏感性和血脂浓度的影响。
在急性给药（第3天）和连续治疗19天（第3 - 21天）后，使用含D[3 - 3H]标记葡萄糖、可变D[3 - 3H]起始剂量和“热”葡萄糖输注的等血糖、高胰岛素葡萄糖钳夹技术评估胰岛素敏感性。在钳夹的基础期和胰岛素刺激期通过同位素测定葡萄糖出现率（Ra）和葡萄糖消失率（Rd）。研究了24例（5例女性）高血压（血压高于年龄和性别的第75百分位数）2型糖尿病患者。患者以双盲方式随机分为每日服用4 mg群多普利（T）组或安慰剂（P）组。
基线（第1天）收缩压（均值±标准差；P组164±14，T组168±13 mmHg）和舒张压（P组93±6，T组98±10 mmHg）相当。在第3天和第21天，两组血压均显著降低（P<0.001）。在群多普利治疗组，除1例患者单次就诊时外，所有患者在第3天和第21天血清群多普利浓度均>200 pg/ml，而安慰剂组未检测到群多普利。T组的体重指数（BMI）高于P组（32.2±5.4对28.3±4.6，P = 0.07）。校正BMI后，两组基础肝葡萄糖输出量（HGO）[P组2.6（95%可信区间2.23 - 3.13），T组1.91（1.33 - 2.51）mg·kg⁻¹·min⁻¹]和钳夹时HGO[P组0.32（ - 0.44 - 1.09），T组0.87（0.40 - 1.34）mg·kg⁻¹·min⁻¹]相似。两组在所有天数的胰岛素敏感性指数相当。整个研究过程中两组总胆固醇浓度相似。甘油三酯浓度在P组显著较低[1.38（1.07 - 1.68）；T组2.14（1.70 - 2.58）mmol/l，P<0.01]，未观察到显著的治疗效果。
群多普利急性给药和连续治疗19天对2型糖尿病和高血压患者的胰岛素敏感性或血浆脂质谱无影响。这些数据支持群多普利在2型糖尿病和高血压患者中代谢中性的观点。
