Impaired fibrinolytic compensation for hypercoagulability in obese patients with type 2 diabetes: Association with increased plasminogen activator inhibitor-1

In patients with type 2 diabetes, fibrinolysis is considered impaired by increased plasma concentrations of plasminogen activator inhibitor (PAI)-1. However, several investigators found both coagulation and fibrinolysis to be activated in these patients. We further characterized the balance between coagulation and fibrinolysis in lean and obese patients with type 2 diabetes. We studied 112 type 2 diabetic patients (66 lean, 46 obese) and 69 age-matched healthy subjects (46 lean, 23 obese). We measured plasma concentrations of fibrinogen and prothrombin F1 +2 (F1 +2) as indicating coagulation activity and plasmin-antiplasmin complex (PAP) and D dimer as indicating fibrinolytic activity. Plasma PAI-1 concentrations also were determined. Plasma concentrations of F1 +2, PAP, D dimer, and PAI-1 were higher in diabetic patients than in control subjects. Plasma fibrinogen and F1 +2 were similar between lean and obese diabetic patients, but plasma PAP and D dimer were significantly lower in obese than lean diabetic patients (P <.0001, P =.0194, respectively). By multivariate analysis, plasma PAI-1 and body mass index (BMI) were independent factors in diabetic patients predicting PAP, while BMI and glycosylated hemoglobin (HbA(1c)) independently predicted D dimer. Plasma PAI-1 concentrations were significantly higher in obese than lean diabetic patients (P <.0001). In conclusions, both coagulation and fibrinolytic systems are enhanced in lean and obese type 2 diabetic patients compared with healthy subjects. Although the degree of activation of coagulation was similar between lean and obese diabetic patients, the fibrinolytic activity was lower in obese than lean patients. Fibrinolytic compensation for hypercoagulation is incomplete in obese patients with type 2 diabetes, partly because of elevated PAI-1 in the blood. Copyright 2002, Elsevier Science (USA). All rights reserved.