title: Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type 1 diabetic patients.
abstract: 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.
authors.affiliation: Section of Internal and Vascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy. iorioa@unipg.it
authors.forename: Alfonso
authors.initials: A
authors.lastname: Iorio
authors.forename: Marco Orsini
authors.initials: MO
authors.lastname: Federici
authors.forename: Evangelia
authors.initials: E
authors.lastname: Mourvaki
authors.forename: Piero
authors.initials: P
authors.lastname: Ferolla
authors.forename: Marta
authors.initials: M
authors.lastname: Piroddi
authors.forename: Anna
authors.initials: A
authors.lastname: Stabile
authors.forename: Alessandra
authors.initials: A
authors.lastname: Timi
authors.forename: Roberta
authors.initials: R
authors.lastname: Celleno
authors.forename: Massimo Massi
authors.initials: MM
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D001780:Blood Coagulation Tests; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016883:Diabetic Ketoacidosis / Q000097:blood / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000378:metabolism*; D005167:Factor VII / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007332:Insulin Infusion Systems; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D050050:Protein Carbonylation; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D014841:von Willebrand Factor; D008315:Malondialdehyde; D005167:Factor VII; D005169:Factor VIII; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator