Dorella M, Giusto M, Da Tos V, Campagnolo M, Palatini P, Rossi G, Ceolotto G, Felice M, Semplicini A, Del Prato S
Institute of Clinical Medicine, University of Padova, Italy.
J Clin Endocrinol Metab. 1996 Apr;81(4):1568-74. doi: 10.1210/jcem.81.4.8636369.
Nine hypertensive patients with body mass indexes between 24-27 kg/m2 and normal glucose tolerance with at least a postchallenge plasma insulin level greater than 360 pmol/L were recruited for a double blind, cross-over study with metformin (850 mg, twice daily) and placebo. Each treatment lasted 1 month. Before and after each treatment, hormone and substrate concentrations were determined, blood pressure was monitored over 24 h, and insulin sensitivity was measured by a euglycemic (4.7 mmol/L) hyperinsulinemic (450 pmol/L) clamp study. Renal cation excretion and erythrocyte membrane cation heteroexchange were measured. Metformin, compared to placebo, did not affect body weight (70 +/- 7 vs. 70 +/- 7 kg), fasting plasma glucose (4.8 +/- 0.1 vs. 4.8 +/- 0.1 mmol/L), total cholesterol (5.38+/0.33 vs. 5.48 +/- 0.38 mmol/L), or triglycerides (1.73 +/- 0.72 vs. 1.91 0.89 mmol/L). Nevertheless, after metformin treatment, the plasma high density lipoprotein cholesterol concentration increased (1.42 +/- 0.18 vs. 1.34 0.16 mmol/L), and the plasma insulin level dropped (62 +/- 10 vs. 88+/- 12 pmol/L; both P < 0.05). Insulin-mediated glucose disposal was higher after metformin treatment (26.1 +/- 2.4 vs. 19.3 +/- 2.3 micromol/min x kg; P < 0.01), whereas hepatic glucose production was completely suppressed. These positive metformin-induced metabolic effects were not associated with a significant change in mean daily blood pressure levels (141 +/- 6/89 +/- 3 vs. 142 +/- 7/90 +/- 3 mm Hg). Compared to placebo, metformin increased the excretion of sodium, potassium, and lithium by enhancing their glomerular filtration rate. Na+/Li+ countertransport was not affected by metformin. However, the apparent affinity for H+ of Na+/H+ exchange was increased, and the Hill coefficient was decreased. In conclusion, 1 month of metformin administration to patients with essential hypertension and normal glucose tolerance 1) reduces the basal plasma insulin concentration, 2) improves whole body insulin-mediated glucose utilization, and 3) improves plasma high density lipoprotein cholesterol levels. Despite these positive effects, metformin did not reduce arterial blood pressure.
招募了9名体重指数在24 - 27kg/m²之间、糖耐量正常且至少餐后血浆胰岛素水平大于360pmol/L的高血压患者，进行一项关于二甲双胍（850mg，每日两次）和安慰剂的双盲交叉研究。每种治疗持续1个月。每次治疗前后，测定激素和底物浓度，监测24小时血压，并通过正常血糖（4.7mmol/L）高胰岛素血症（450pmol/L）钳夹研究测量胰岛素敏感性。测量肾阳离子排泄和红细胞膜阳离子异质交换。与安慰剂相比，二甲双胍不影响体重（70±7 vs. 70±7kg）、空腹血糖（4.8±0.1 vs. 4.8±0.1mmol/L）、总胆固醇（5.38±0.33 vs. 5.48±0.38mmol/L）或甘油三酯（1.73±0.72 vs. 1.91±0.89mmol/L）。然而，二甲双胍治疗后，血浆高密度脂蛋白胆固醇浓度升高（1.42±0.18 vs. 1.34±0.16mmol/L），血浆胰岛素水平下降（62±10 vs. 88±12pmol/L；均P<0.05）。二甲双胍治疗后胰岛素介导的葡萄糖处置增加（26.1±2.4 vs. 19.3±2.3μmol/min·kg；P<0.01），而肝葡萄糖生成被完全抑制。二甲双胍诱导的这些积极代谢效应与平均每日血压水平的显著变化无关（141±6/89±3 vs. 142±7/90±3mmHg）。与安慰剂相比，二甲双胍通过提高肾小球滤过率增加钠、钾和锂的排泄。Na⁺/Li⁺逆向转运不受二甲双胍影响。然而，Na⁺/H⁺交换对H⁺的表观亲和力增加，希尔系数降低。总之，对原发性高血压且糖耐量正常的患者给予1个月的二甲双胍治疗：1）降低基础血浆胰岛素浓度，2）改善全身胰岛素介导的葡萄糖利用，3）提高血浆高密度脂蛋白胆固醇水平。尽管有这些积极作用，但二甲双胍并未降低动脉血压。
