Iorio Alfonso, Federici Marco Orsini, Mourvaki Evangelia, Ferolla Piero, Piroddi Marta, Stabile Anna, Timi Alessandra, Celleno Roberta, Benedetti Massimo Massi
Section of Internal and Vascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy.
Thromb Haemost. 2007 Sep;98(3):635-41.
Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.
文献综述表明，频繁发生高酮血症的糖尿病患者血栓形成并发症的发生率有所增加。然而，酮症促进糖尿病患者血管疾病的机制尚不清楚。本研究的目的是调查I型糖尿病患者在持续皮下胰岛素输注（CSII）中断后高酮血症状态下止血参数和氧化应激标志物的早期变化。8名接受CSII治疗的I型糖尿病患者经历了4小时的泵中断。测量血糖、胰岛素和3-羟基丁酸以验证代谢反应。在CSII中断前后进行静脉闭塞（VO）试验，以测定tPA和PAI-1活性及其抗原水平。分别通过一期PT和PTT方法评估凝血因子VII和VIII。通过ELISA测定TF、vWF、tPA和PAI-1抗原，而使用显色法测定tPA和PAI-1活性。分别通过HPLC和分光光度法测定血浆丙二醛（MDA）和蛋白质羰基（PCG）水平。在胰岛素缺乏期后，VO后tPA抗原水平显著降低（P = 0.0391），而TF以及VO后PAI-1活性和抗原水平显著升高（分别为P = 0.0156和P = 0.0234）。血浆MDA和PCG水平分别比基线值高1.88倍和1.74倍。总之，纤维蛋白溶解潜能的损害以及TF、MDA和PCG水平的升高可能会增加酮症期间动脉和静脉血栓形成的风险。因此，早期检测糖尿病患者的高酮血症可能有助于预防危及生命的血管事件。
