INCREASED PROTHROMBIN FRAGMENT-1-DIMER IN FIRST-DEGREE RELATIVES OF TYPE-2 DIABETIC-PATIENTS - PRETHROMBOTIC STATE IN RELATIVES OF TYPE-2 DIABETIC-PATIENTS(2 AND D)

To evaluate whether or not activated coagulation is present in the pre clinical phases of type 2 diabetes mellitus, we studied 46 non-diabeti c first-degree relatives of type 2 diabetic patients and 21 matched co ntrols with no family history of diabetes. We determined the plasma le vels of prothrombin fragment 1+2, D-dimer, fibrinogen, plasminogen act ivator inhibitor type 1, tissue plasminogen activator, von Willebrand factor and coagulation factors VII and VIII. Glucose tolerance, beta-c ell 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 0.6 8 nmol . l(-1); P=0.0001) and D-dimer (331 vs 254 mu g . l(-1) UEF; P= 0.018) were higher in relatives, without significant differences in th e 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 d ifferences in insulin sensitivity. Fifteen relatives were glucose-into lerant and had lower beta-cell function and insulin sensitivity than g lucose-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 ac tivated coagulation, even in the absence of minor degrees of glucose i ntolerance. These abnormalities can play a role in the pathogenesis of cardiovascular diseases frequently seen at diagnosis of type 2 diabet es.