Increased plasminogen activator inhibitor-1 (PAI-1) and decreased tissue-plasminogen activator (t-PA) activities lead to impaired fibrinolysis, which is critical for cardiovascular disease. We studied these hemostatic factors at fasting state and after an oral fat load in 12 type 2 diabetic and 17 nondiabetic obese adolescents, matched for age, sex, body mass index, and sexual maturation. Plasma PAI-1, t-PA, and glucose as well as serum C-peptide, insulin, total cholesterol, triglyceride, and HDL and LDL cholesterol levels were measured at 0, 2, 4, and 6 h after the fat load. Metabolic responses were expressed as the area under the curve (AUC). PAI-1 activities were signifi-cantly greater in patients than in control subjects fasting, 23.4 ± 2.6 versus 12.9 ± 2.0 U/mL (p < 0.004); AUC, 101.7 ± 12.1 versus 57.6 ± 6.5 U · h-1 · mL-1 (p < 0.003) . Fasting t-PA activities were significantly lower in the patients than in the control subjects (0.8 ± 0.3 versus 6.5 ± 2.7 U/mL; p < 0.001). Triglyceride was the only lipid parameter that was significantly different in the patients than in the control subjects fasting, 1.5 ± 0.2 versus 0.9 ± 0.1 mM (p < 0.05); AUC, 15.7 ± 2.9 versus 7.9 ± 0.6 mmol· h-1· L-1 (p < 0.02) . The PAI-1 activities decreased significantly during the loading tests (p < 0.0001), whereas the t-PA activities did not change. Insulin resistance estimated by the homeostasis model assessment was greater in the patients than in the control subjects (14.4 ± 2.8 versus 4.6 ± 0.7; p < 0.0001). We conclude that elevated PAI-1 and diminished t-PA activities, suggestive of suppressed fibrinolysis, are present in our adolescents with type 2 diabetes; adding another risk factor for cardiovascular disease and acute high fat load does not further negatively affect this suppressed fibrinolysis.
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