The effect of the relationship between tissue-type plasminogen activator and plasminogen activator inhibitor type 1 on tissue-type plasminogen activator activity in insulin-dependent diabetes mellitus

Background: Changed fibrinolytic activity in insulin-dependent diabetes mellitus (IDDM) may give information on the interaction between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Aim: To investigate the relationship between t-PA and PAI-1 in IDDM patients with and without diabetic nephropathy. Patients: 17 IDDM patients with normal urine albumin excretion (< 30 mg/24-h, normoalbuminuria), 19 IDDM patients with albumin excretion in the range 30-300 mg/24-h (incipient nephropathy) and 13 IDDM patients with albumin excretion > 300 mg/24-h (clinical nephropathy). 14 nondiabetic subjects served as controls. Results: Given as mean (range). t-PA antigen was lower in IDDM irrespective of the level of albuminuria (3.3 (1.2-5.5) ng/ml, p < 0.05; 4.2 (1.4-12.9) ng/ml, p = 0.07 and 3.4 (1.2-8.7) ng/ml, p < 0.05 vs. 5.4 (2.1-9.6) ng/ml in non-diabetic controls). PAT-1 antigen was also lower in IDDM with normoalbuminuria (4.2 (2.3-7.0) ng/ml vs. 11.0 (3.4-29.8) ng/ml in non-diabetic controls, p < 0.001) and in incipient and clinical nephropathy the pattern was the same (5.9 (1.1-16.7) ng/ml, p < 0.05 and 5.8 (2.7-10.3) ng/ml, p = 0.07 vs. non-diabetic controls, respectively). t-PA activity was increased in IDDM with normoalbuminuria (0.7 (0.4-3.3) iU/ml p < 0.05) compared to the level in non-diabetic controls (0.6 (0.0-2.2) IU/ml), while the level in nephropathy was not different from non-diabetic controls. Conclusion: A shift in the relation between t-PA and PAI-1 antigen levels result in an increased activity of t-PA in IDDM patients without nephropathy.