Watanabe Masaki, Inukai Kouichi, Sumita Takashi, Ikebukuro Kaori, Ito Daisuke, Kurihara Susumu, Ono Hiraku, Awata Takuya, Katayama Shigehiro
Department of Endocrinology and Diabetes, Saitama Medical University, Saitama, Japan.
Intern Med. 2010;49(17):1843-7. doi: 10.2169/internalmedicine.49.3189. Epub 2010 Sep 1.
PPARgamma agonists are widely used in type 2 diabetic patients to reduce insulin resistance. Recently, telmisartan, an AT1 receptor antagonist, was reported to function as a partial agonist of PPARgamma based on in vitro experiments. The aim of the present study was to investigate whether the PPARgamma enhancing activity of telmisartan is exerted clinically in diabetic patients.
We compared the effects of telmisartan with those of candesartan, on insulin sensitivity, the serum levels of various adipocytokines and oxidative stress.
In total, 85 Japanese type 2 diabetic patients with hypertension, maintained on 8 mg per day of candesartan, were randomly assigned to the TM group (candesartan switched to 40 mg of telmisartan, n=38) or the CD group (no treatment change, n=47).
After 3 months, oxidized lipids were significantly decreased only in the TM group. Although the homeostasis assessment model of insulin resistance (HOMA-R) tended to be improved and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be increased only in the TM group, these alterations were too small to be significant by unpaired t-test. Interestingly, in subgroup analysis, the alterations of HOMA-R, serum concentrations of oxidized lipids, and HMW adiponectin were more apparent in obese TM group subjects and the changes reached statistical significance.
Switching from candesartan to telmisartan in obese subjects increases serum adiponectin and improves both insulin resistance and oxidative stress, while these effects were not statistically apparent in the total patient population. These results support the idea that telmisartan exerts its PPARgamma enhancing activity clinically in obese type 2 diabetic patients.
PPARγ激动剂广泛应用于2型糖尿病患者以降低胰岛素抵抗。最近，据体外实验报道，血管紧张素Ⅱ1型受体（AT1）拮抗剂替米沙坦可作为PPARγ的部分激动剂。本研究旨在探讨替米沙坦增强PPARγ的活性在糖尿病患者中是否具有临床作用。
我们比较了替米沙坦与坎地沙坦对胰岛素敏感性、各种脂肪细胞因子血清水平和氧化应激的影响。
总共85名日本2型糖尿病合并高血压患者，每日服用8mg坎地沙坦，被随机分为替米沙坦组（将坎地沙坦换为40mg替米沙坦，n = 38）或坎地沙坦组（未改变治疗，n = 47）。
3个月后，仅替米沙坦组的氧化脂质显著降低。虽然仅替米沙坦组的胰岛素抵抗稳态评估模型（HOMA-R）有改善趋势，高密度脂蛋白胆固醇（HDL-胆固醇）和高分子量脂联素的血清浓度有升高趋势，但这些变化太小，经不成对t检验无统计学意义。有趣的是，在亚组分析中，肥胖替米沙坦组受试者的HOMA-R、氧化脂质血清浓度和高分子量脂联素的变化更明显，且这些变化具有统计学意义。
肥胖受试者从坎地沙坦换用替米沙坦可增加血清脂联素，改善胰岛素抵抗和氧化应激，而在全部患者人群中这些作用无统计学意义。这些结果支持替米沙坦在肥胖2型糖尿病患者中具有临床增强PPARγ活性的观点。
