First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Kitakyushu 807-8555, Japan.
Adv Ther. 2012 Jul;29(7):635-44. doi: 10.1007/s12325-012-0032-x. Epub 2012 Jul 20.
The clinical dose of telmisartan necessary for activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma) has not been established. The authors investigated the effect of high-dose telmisartan on serum levels of the high-molecular-weight (HMW) adiponectin in patients with diabetes and hypertension.
In this open-label, prospective, randomized study, patients with type 2 diabetes and hypertension with poor control of blood pressure by 40 mg/day telmisartan were randomly assigned into the telmisartan 80 mg/day (Tel80) group (dose increase from 40 to 80 mg/day) or the telmisartan 40 mg + amlodipine 5 mg (Tel40 + Aml5) group. Serum levels of HMW adiponectin and parameters of glucose and lipid metabolism were measured at baseline and end of 3-months of treatment.
Although the antihypertensive effects of the two doses of telmisartan were similar, a significant increase in HMW adiponectin levels was noted only in the Tel80 group. The increase was evident particularly in a group of patients whose HMW adiponectin levels were less than 4.0 μg/dL. A significant improvement in homeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, was also observed in the Tel80 group only.
In diabetic patients with hypertension, high-dose telmisartan increased HMW adiponectin levels and improved insulin resistance through activation of PPAR-gamma.
尚未确定替米沙坦发挥过氧化物酶体增殖物激活受体γ(PPAR-γ)活性的临床剂量。作者研究了高剂量替米沙坦对糖尿病和高血压患者血清高分子量(HMW)脂联素水平的影响。
在这项开放标签、前瞻性、随机研究中,将血压控制不佳(40mg/天替米沙坦)的 2 型糖尿病和高血压患者随机分为替米沙坦 80mg/天(Tel80)组(剂量从 40 增加到 80mg/天)或替米沙坦 40mg+氨氯地平 5mg(Tel40+Aml5)组。在基线和治疗 3 个月末测量 HMW 脂联素和葡萄糖及脂质代谢参数。
尽管两种剂量的替米沙坦的降压作用相似,但仅在 Tel80 组观察到 HMW 脂联素水平显著升高。在 HMW 脂联素水平低于 4.0μg/dL 的患者中,这种升高更为明显。仅在 Tel80 组观察到胰岛素抵抗的稳态模型评估(HOMA-IR)显著改善,这是衡量胰岛素抵抗的一个指标。
在患有高血压的糖尿病患者中,高剂量替米沙坦通过激活 PPAR-γ 增加 HMW 脂联素水平并改善胰岛素抵抗。