THE EFFECT OF GLICLAZIDE ON PLASMA UROKINASE-RELATED FIBRINOLYSIS - THE RESULTS FROM AN EXPLORATORY-STUDY

Late diabetes is characterized by accelerated arteriosclerosis, increa sed incidence of myocardial infarction, and excessive fibrin depositio n in the microcirculation. It is believed that drugs which enhance end ogenous fibrinolysis might retard or even reverse these complications. Gliclazide, a second generation sulphonylurea, has previously been re ported to increase the protein concentration of t-PA in diabetic patie nts. Presently, we have in type 1 diabetic patients studied the effect of gliclazide on inhibition and activation of u-PA. Twenty-three non- obese male type 1 diabetics without residual beta-cell function were i ncluded in the study. The patients received gliclazide for a period of 6 months either in a dose of 160 mg/day (n = 11) or in a dose of 240 mg/day (n = 12). Blood samples were collected immediately before, afte r 3 months and after 6 months of treatment, and finally 1 month after treatment had been stopped. The protein concentrations of u-PA, PAI-1 and PAP-complexes were determined hy ELISA methods. Activatable scu-PA was determined by a Bio-Immune-Assay. Friedman's X(2) test was used f or statistical analysis. When all patients were combined we observed t hat the concentration of PAI-1 antigen decreased significantly (p < 0. 02) during treatment while PAP-complexes remained stable. When the two groups of patients were separated we observed that the concentrations of both u-PA. (p < 0.01) and activatable scu-PA (p < 0.01) decreased significantly in patients treated with 160 mg of gliclazide while the concentrations of all the variables studied remained unchanged in pati ents receiving 240 mg. Insulin demand, metabolic variables, and weight remained stable during the study period. The results from the present exploratory study suggest that gliclazide has the capability to affec t activatable scu-PA, u-PA, and PAI-1 in a subset of type 1 diabetic p atients. Since effective fibrinolysis (PAP-complexes) remains unchange d these observations might indicate an effect on endothelial cell func tion.