The Effect of Near-Normoglycemic Control on Plasma Factor VIII/von Willebrand Factor and Fibrin Degradation Products in Insulin-Dependent Diabetic Patients*

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Abstract
Diabetic patients have elevated plasma levels of factor VIII/von Willebrand factor (F-VIII/vWF), and such elevations have been linked to vascular endothelial injury. In a prospective study we investigated the effect of metabolic regulation on the plasma levels of F VIII/vWF and cross-linked fibrin degradation products (XL-FDP), and indicator of intravascular coagulation, in 15-insulin-dependent diabetic patients who had no demonstrable vascular abnormalities. Eight patients had newly diagnosed diabetes, and 7 had been diabetic for an average of 12 yr. The patients were tested before and 1,2,4 and 8 weeks after the start of a structured diabetes education and care program, including introduction of basal-bolus form of insulin treatment. Treatment for 8 weeks resulted in a highly significant improvement of metabolic control [hemoglobin A1c, 11.1 .+-. 1.3% (.+-.SD) sv 6.8 .+-. 1.0%; plasma fructosamine, 4.8 .+-. 1.0 vs 2.9 .+-. 0.7 mmol/L; plasma glucose, 13.5 .+-. 4.2 vs 6.3 .+-. 2.2 mmol/L; P < 0.0001, respectively]. Compared to age- and sex-matched normal subjects, plasma activity of factor VIII (F VIII:C) was significantly elevated in the diabetic patients initially (1.5 .+-. 0.6 vs. 1.0 .+-. 0.1 10-3 U/L; P < 0.01). After 2 weeks of intensified therapy it was 1.1 .+-. 0.4 .times. 103 U/L. The mean plasma vWF value also was significantly elevated initially [vWF antigen, 1.8 .+-. 0.7; normal group, 0.9 .+-. 0.1 .times. 10-3 u/L (P < 0.01); vWF ristocetin cofactor activity, 1.9 .+-. 0.9; normal group, 1.0 .+-. 0.3 .times. 103 U/L (P < 0.0010] and decreased significantly after only 1 week of therapy. In the following 7-week period plasma vWF remained near normal. Plasma XL-FDP levels were elevated in all patients initially (190 .+-. 150; normal group, 35 .+-. 30 .mu.g/L): the value was almost abnormal in the patients with newly diagnosed disease (300 .+-. 150 .mu.g/L), indicating intravascular fibrin formation. The mean XL-FDP level declined significantly in the patients with newly diagnosed diabetes after 1 week of therapy; in the other patients, however, XL-FDP levels remained slightly elevated. In all 15 patients the plasma F VIII:C and XL-FDP levels were correlated significantly at all times. The plasma vWF and XL-FDP levels were correlated after 1, 2 4, and 8 weeks of treatment as were the plasma vWF levels and glucose concentrations before and 1 and 2 weeks after the start of treatment program. These results indicate that near-normalization of glycemic control leads to an improvement in endothelial cell function and a reduction of hypercoagulation in insulin-dependent diabetic patients without demonstrable vascular abnormalities.

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