The effect of near-normoglycemic control on plasma factor VIII/von Willebrand factor and fibrin degradation products in insulin-dependent diabetic patients.
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 Aic, 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 less than 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 10(3) U/L; P less than 0.01). After 2 weeks of intensified therapy it was 1.1 +/- 0.4 x 10(3) 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 10(3) U/L (P less than 0.01); vWF ristocetin cofactor activity, 1.9 +/- 0.9; normal group, 1.0 +/- 0.3 x 10(3) U/L (P less than 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 micrograms/L): the value was most abnormal in the patients with newly diagnosed disease (300 +/- 150 micrograms/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.(ABSTRACT TRUNCATED AT 400 WORDS)
Vukovich
T C
TC
Department of Medical Physiology, University of Vienna, Austria.
Schernthaner
G
G
Knöbi
P N
PN
Hay
U
U
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D019270:Fructosamine; D006442:Glycated Hemoglobin / Q000032:analysis; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014841:von Willebrand Factor / Q000032:analysis*
D001786:Blood Glucose; D005338:Fibrin Fibrinogen Degradation Products; D019270:Fructosamine; D006442:Glycated Hemoglobin; D006595:Hexosamines; D007328:Insulin; D014841:von Willebrand Factor