title: Increased prothrombin fragment 1 + 2 and D-dimer in first-degree relatives of type 2 diabetic patients. Prethrombotic state in relatives of type 2 diabetic patients.
abstract: To evaluate whether or not activated coagulation is present in the preclinical phases of type 2 diabetes mellitus, we studied 46 non-diabetic first-degree relatives of type 2 diabetic patients and 21 matched controls with no family history of diabetes. We determined the plasma levels of prothrombin fragment 1 + 2, D-dimer, fibrinogen, plasminogen activator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-cell function and insulin sensitivity were assessed in all subjects by a continuous glucose infusion of 5 mg.kg ideal body weight-1.min-1 for 60 min with model assessment of glucose, insulin and C-peptide values. Plasma levels of prothrombin fragment 1 + 2 (median 1.24 vs 0.68 nmol.l-1; P = 0.0001) and D-dimer (331 vs 254 micrograms.l-1 UEF; P = 0.018) were higher in relatives, without significant differences in the other haemostatic variables. Relatives showed higher fasting (5.5 vs 4.9 mmol.l-1, P = 0.004) and post-infusion (9.3 vs 8.3 mmol.l-1, P = 0.02) serum glucose, no differences in insulin or C-peptide levels, lower beta-cell function (122% vs 147%; P = 0.02) and no significant differences in insulin sensitivity. Fifteen relatives were glucose-intolerant and had lower beta-cell function and insulin sensitivity than glucose-tolerant relatives. Both subsets of relatives exhibited higher levels of prothrombin fragment 1 + 2 and D-dimer than control subjects. Thus, first-degree relatives of type 2 diabetic patients present an activated coagulation, even in the absence of minor degrees of glucose intolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabetes.
authors.affiliation: Endocrine Unit, CSU Bellvitge, L Hospitalet de Llobregat, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Castañer
authors.forename: I
authors.initials: I
authors.lastname: Camps
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Real
authors.forename: P
authors.initials: P
authors.lastname: Domenech
authors.forename: F
authors.initials: F
authors.lastname: Martínez-Brotons
mesh_terms: D000328:Adult; D000367:Age Factors; D001779:Blood Coagulation Factors / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis*; D011516:Prothrombin / Q000032:analysis*; D012307:Risk Factors; D018709:Statistics, Nonparametric
chemical_list: D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D011498:Protein Precursors; C036309:fibrin fragment D; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin