Furuhashi Masato, Ura Nobuyuki, Higashiura Katsuhiro, Murakami Hideyuki, Tanaka Marenao, Moniwa Norihito, Yoshida Daisuke, Shimamoto Kazuaki
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan.
Hypertension. 2003 Jul;42(1):76-81. doi: 10.1161/01.HYP.0000078490.59735.6E. Epub 2003 Jun 9.
Adiponectin, an adipocyte-derived protein, has been suggested to play an important role in insulin sensitivity. We examined the association between insulin sensitivity (M value) evaluated by the euglycemic-hyperinsulinemic glucose clamp and adiponectin concentrations in 30 essential hypertensives (EHT) and 20 normotensives (NT) and investigated the effect of blockade of the renin-angiotensin system (RAS) on adiponectin concentrations. EHT were divided into 12 insulin-resistant EHT (EHT-R) and 18 non-insulin-resistant EHT (EHT-N) using mean-1 SD of the M value in NT. There were no intergroup differences in age, gender, and body mass index (BMI). EHT-R had significantly higher levels of insulin and triglyceride and lower levels of adiponectin than did NT and EHT-N. EHT-R had higher levels of free fatty acid and lower levels of high-density lipoprotein (HDL) cholesterol than did EHT-N. Adiponectin concentrations were positively correlated with M value and HDL cholesterol and negatively correlated with BMI, insulin, free fatty acid, and triglyceride but not with blood pressure. M value, BMI, and HDL cholesterol were independent determinants of adiponectin concentrations in multiple and stepwise regression analyses. Sixteen EHT were treated with an angiotensin-converting enzyme inhibitor (temocapril, 4 mg/d; n=9) or an angiotensin II receptor blocker (candesartan, 8 mg/d; n=7) for 2 weeks. Treatment with temocapril or candesartan significantly decreased blood pressure and increased M value and adiponectin concentrations but did not affect BMI and HDL cholesterol. These results suggest that hypoadiponectinemia is related to insulin resistance in essential hypertension and that RAS blockade increases adiponectin concentrations with improvement in insulin sensitivity.
脂联素是一种脂肪细胞衍生蛋白,被认为在胰岛素敏感性方面发挥重要作用。我们检测了30例原发性高血压患者(EHT)和20例血压正常者(NT)中通过正常血糖-高胰岛素葡萄糖钳夹评估的胰岛素敏感性(M值)与脂联素浓度之间的关联,并研究了肾素-血管紧张素系统(RAS)阻断对脂联素浓度的影响。根据NT中M值的均值减1个标准差,将EHT分为12例胰岛素抵抗的EHT(EHT-R)和18例非胰岛素抵抗的EHT(EHT-N)。年龄、性别和体重指数(BMI)在组间无差异。与NT和EHT-N相比,EHT-R的胰岛素和甘油三酯水平显著更高,脂联素水平更低。与EHT-N相比,EHT-R的游离脂肪酸水平更高,高密度脂蛋白(HDL)胆固醇水平更低。脂联素浓度与M值和HDL胆固醇呈正相关,与BMI、胰岛素、游离脂肪酸和甘油三酯呈负相关,但与血压无关。在多元逐步回归分析中,M值、BMI和HDL胆固醇是脂联素浓度的独立决定因素。16例EHT患者接受血管紧张素转换酶抑制剂(替莫卡普利,4mg/d;n=9)或血管紧张素II受体阻滞剂(坎地沙坦,8mg/d;n=7)治疗2周。替莫卡普利或坎地沙坦治疗显著降低血压,增加M值和脂联素浓度,但不影响BMI和HDL胆固醇。这些结果表明,低脂联素血症与原发性高血压中的胰岛素抵抗有关,RAS阻断可增加脂联素浓度并改善胰岛素敏感性。