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

Department of Medical Physiology Vienna, Austria
Department of Medicine II, University of Vienna Vienna, Austria
Department of Medicine I, Rudolfstiftung Hospital Vienna, Austria

Address all correspondence and requests for reprints to: Professor Guntram Schernthaner, Department of Medicine I, Rudolfstiftung Hospital, Juchgasse 25, Vienna A1030, Austria.

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), an 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 a basal-bolus form of insulin treatment. Treatment for 8 weeks resulted in a highly significant improvement of metabolic control [hemoglobin A_lc, 11.1 ± 1.3% (±SD) vs. 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 X 10³ U/L; P < 0.01). After 2 weeks of intensified therapy it was 1.1 ± 0.4 x 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 x 10³ U/L (P < 0.01); vWF ristocetin cofactor activity, 1.9 ± 0.9; normal group, 1.0 ± 0.3 x 10³ U/L (P < 0.001)] 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 µg/L): the value was most abnormal in the patients with newly diagnosed disease (300 ± 150 µg/L), indicating intravascular fibrin formation. The mean XL-FDP level declined significantly in the patients with newly diagnosed diabtes after 1 week of therapy; in the other patients, however, XL-FDP levels remained slightly elevated. In all 15 patients the plasma F VIIIC 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.

^* This work was supported by Anton Dreher-Gedächtnisschenkung Grant 88/87.

Received October 21, 1988.

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