Landin K, Tengborn L, Smith U
Department of Medicine II, Sahlgrenska Hospital, University of Göteborg, Sweden.
J Intern Med. 1991 Feb;229(2):181-7. doi: 10.1111/j.1365-2796.1991.tb00328.x.
Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.
胰岛素抵抗和高胰岛素血症可能在高血压的发生及其伴随的代谢异常中起重要作用。为了研究这种可能性，作为一项初步研究和患者自身对照，对9名未经治疗的高血压非肥胖、非糖尿病、不吸烟的中年男性给予二甲双胍850毫克，每日两次，治疗6周。二甲双胍降低了总胆固醇和低密度脂蛋白胆固醇（P<0.01）、甘油三酯（P<0.01）、空腹血浆胰岛素（P<0.01）和C肽水平（P<0.02）。通过正常血糖钳夹技术测量的胰岛素作用指标葡萄糖处置增加（P<0.001）。组织型纤溶酶原激活剂（t-PA）活性增加（P<0.02），t-PA抗原降低（P<0.01），而纤溶酶原激活剂抑制剂（PAI-1）和纤维蛋白原不受二甲双胍治疗的影响。体重保持不变。停用二甲双胍后，血压和代谢均恢复到初始水平。总之，二甲双胍治疗增加了胰岛素作用，降低了血压，改善了代谢危险因素谱，并倾向于增加这些轻度高血压患者的纤溶活性。这些结果支持胰岛素抵抗在高血压中起作用的观点，并可能为缓解与心血管疾病相关的异常开辟一个新领域。
