title: Thrombomodulin and induced tissue factor expression on monocytes as markers of diabetic microangiopathy: a prospective study on hemostasis and lipoproteins in insulin-dependent diabetes mellitus.
abstract: Vascular complications are the main cause of morbidity in diabetes mellitus. To evaluate lipoprotein and hemostatic parameters and their relationship with clinically detectable microangiopathy, we studied 58 insulin-dependent diabetes mellitus patients and 60 controls matched for age, sex, and body mass index. Thirteen patients presented clinically detectable microangiopathy (8 retinopathy and 5 both retinopathy and microalbuminuria). A cross-sectional study of lipid profile, coagulation parameters, and a flow-cytometric evaluation of tissue factor expression in normal monocytes induced by patient plasma were performed. Patients were re-evaluated for microangiopathy in a 3-year median follow-up. Patients showed triglyceride enrichment in low (P = 0.00002) and high density lipoproteins (P = 0.004) and increased levels of D-dimer (P < 0.00001), prothrombin fragment 1 + 2 (P < 0.00001), and thrombin-antithrombin III complex (P = 0.0001). Patients with clinically detectable microangiopathy had increased type 1 plasminogen activator inhibitor (P = 0.00001), thrombomodulin (P = 0.02), and induced monocyte tissue factor expression (P < 0.00001). Nine patients developed clinically detectable microangiopathy in the follow-up and the only predictive variable was increased induced tissue factor expression. In conclusion, in these patients elevated thrombin and fibrin generation reflects a hypercoagulable state but clinically detectable microangiopathy seems related to endothelial cell injury markers and to increased induced tissue factor expression on monocytes.
authors.affiliation: Department of Endocrinology, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Reverter
authors.forename: J C
authors.initials: JC
authors.lastname: Reverter
authors.forename: D
authors.initials: D
authors.lastname: Tàssies
authors.forename: F
authors.initials: F
authors.lastname: Rius
authors.forename: J
authors.initials: J
authors.lastname: Monteagudo
authors.forename: J
authors.initials: J
authors.lastname: Rubiés-Prat
authors.forename: G
authors.initials: G
authors.lastname: Escolar
authors.forename: A
authors.initials: A
authors.lastname: Ordinas
authors.forename: A
authors.initials: A
authors.lastname: Sanmarti
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003925:Diabetic Angiopathies / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006487:Hemostasis; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011446:Prospective Studies; D018180:Thrombomodulin / Q000097:blood*; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008055:Lipids; D008074:Lipoproteins; D018180:Thrombomodulin; D013925:Thromboplastin