FREE-RADICAL ACTIVITY AND HEMOSTATIC FACTORS IN NIDDM PATIENTS WITH AND WITHOUT MICROALBUMINURIA

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAl-1), tissue plasminogen activator (t-PA), and plasmin activity (B(beta-15-42)) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuria patients compared with control subjects (P < 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P < 0.05) and control subjects (P < 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P < 0.01). Except for B(beta-15-42), all the hemostatic variables were increased (P < 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P < 0.03) and t-PA (P < 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in NIDDM patients with microalbuminuria.