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肝素治疗对肥胖非胰岛素依赖型糖尿病患者止血异常的影响。

Effects of heparin treatment on hemostatic abnormalities in obese non-insulin-dependent diabetic patients.

作者信息

Avellone G, di Garbo V, Cordova R, Rotolo G, Raneli G, de Simone R, Bompiani G

机构信息

Institute of Clinical Medicine, University of Palermo, Italy.

出版信息

Metabolism. 1997 Aug;46(8):930-4. doi: 10.1016/s0026-0495(97)90082-2.

Abstract

This study was conducted to identify the mechanisms responsible for coagulative and fibrinolytic alterations and to study the effects of a short-term treatment with low-dose heparin on hemostatic abnormalities in obese non-insulin-dependent diabetes mellitus (NIDDM) patients. Four groups of age- and sex-matched patients were studied: (1) lean nondiabetic subjects (n = 30) with a body mass index (BMI) less than 25 kg/m2 (lean control subjects), (2) obese nondiabetic subjects (n = 30) with a BMI greater than 30 kg/m2 (obese control subjects), (3) lean NIDDM patients (n = 30), and (4) obese NIDDM patients (n = 30). All subjects were tested on the following parameters: fibrinogen, factor VII, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), tissue plasminogen activator (t-PA) antigen (Ag) before and after venous occlusion (VO), and plasminogen activator inhibitor type-1 (PAI-1) activity pre- and post-VO. In addition, all these parameters were evaluated in obese NIDDM patients after 10 days of treatment with a single dose of 12,500-U/d subcutaneous calcium heparin and after a 10-day washout period. At baseline, obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients displayed significantly (P < .01) higher levels of fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO and significantly (P < .01) lower levels of t-PA(Ag) post-VO. In obese NIDDM patients treated with heparin fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO levels significantly (P < .01) decreased and t-PA(Ag) post-VO levels significantly (P < .01) increased at the end of treatment. Our findings demonstrate in obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients the hemostatic abnormalities contributing to an enhanced risk of thrombotic complications. We conclude that in obese NIDDM patients, short-term treatment with heparin may reduce this thrombophilic state and have a potential benefit in the progression of diabetic microvascular and macrovascular disease and needs further investigation.

摘要

本研究旨在确定导致凝血和纤溶改变的机制,并研究低剂量肝素短期治疗对肥胖非胰岛素依赖型糖尿病(NIDDM)患者止血异常的影响。研究了四组年龄和性别匹配的患者:(1)体重指数(BMI)小于25kg/m²的瘦型非糖尿病受试者(n = 30)(瘦型对照受试者),(2)BMI大于30kg/m²的肥胖非糖尿病受试者(n = 30)(肥胖对照受试者),(3)瘦型NIDDM患者(n = 30),以及(4)肥胖NIDDM患者(n = 30)。所有受试者均接受以下参数检测:纤维蛋白原、凝血因子VII、凝血酶原片段1 + 2(F1 + 2)、凝血酶 - 抗凝血酶III复合物(TAT)、静脉闭塞(VO)前后的组织纤溶酶原激活物(t-PA)抗原(Ag),以及VO前后的纤溶酶原激活物抑制剂-1(PAI-1)活性。此外,在肥胖NIDDM患者接受单剂量12,500-U/d皮下注射钙肝素治疗10天后以及10天洗脱期后,对所有这些参数进行评估。基线时,肥胖非糖尿病受试者、瘦型NIDDM患者,尤其是肥胖NIDDM患者,其纤维蛋白原、凝血因子VII、F1 + 2、TAT、VO前的t-PA(Ag)以及VO前后的PAI-1水平显著(P <.01)升高,而VO后的t-PA(Ag)水平显著(P <.01)降低。在接受肝素治疗的肥胖NIDDM患者中,治疗结束时纤维蛋白原、凝血因子VII、F1 + 2、TAT、VO前的t-PA(Ag)以及VO前后的PAI-1水平显著(P <.01)降低,而VO后的t-PA(Ag)水平显著(P <.01)升高。我们的研究结果表明,在肥胖非糖尿病受试者、瘦型NIDDM患者,尤其是肥胖NIDDM患者中,存在导致血栓形成并发症风险增加的止血异常。我们得出结论,在肥胖NIDDM患者中,肝素短期治疗可能会降低这种血栓形成倾向,并对糖尿病微血管和大血管疾病的进展具有潜在益处,这需要进一步研究。

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