Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolescents with type 2 diabetes and obesity.
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 significantly 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 [corrected] . 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.
Umpaichitra
Vatcharapan
V
Department of Pediatrics, Brookdale University Hospital and Medical Center [corrected] Brooklyn, NY 11212, USA. vumpaich@brookdale.edu
Hussain
M Mahmood
MM
Castells
Salvador
S
D000293:Adolescent; D019540:Area Under Curve; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting; D006801:Humans; D008913:Minority Groups; D009765:Obesity / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D019518:Postprandial Period; D010959:Tissue Plasminogen Activator / Q000097:blood*
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator