Studies on fibrin network structure in human plasma. Part II--Clinical application: diabetes and antidiabetic drugs

Using measurements of fibrin fibre thickness (microT) derived from turbidity and permeability (tau) of clotted plasma, it has been found that glucose in vitro added to plasma decreases permeability of the network despite unaltered fibrinogen conversion. Fibrin fibre thickness (microT) in uncontrolled diabetes is found significantly reduced. In diabetic plasma the degree of conversion to fibrin is similar to that in age and sex matched plasma from non-diabetics: the effect on fibrin network and fibre thickness probably arises from glycosylation of fibrinogen. Studies with Gliclazide, Metformin, Glibenclamide and insulin have shown that while all other drugs tested have no effect, Gliclazide increases fibrin fibre thickness (microT) significantly, diminishes tensile strength and reduces permeability. In separate experiments lysability of 125I-labelled fibrin networks developed in the presence of all four hypoglycaemic agents by tissue activator was tested. Networks developed in the presence of Metformin were found to lyse more quickly, followed by insulin and Gliclazide. Alterations induced in fibrin networks in diabetes may be nullified by some oral hypoglycaemic agents such as Gliclazide and not by others. Whether nullification of such changes has long-term effects in reducing the incidence of vascular disease in diabetics remains to be established.