Influence of glyco-oxidation on complexes between fibrin(ogen) and insulin-like growth factor-binding protein-1 in patients with diabetes mellitus type 2

Abstract

Fibrinogen and insulin-like growth factor-binding protein-1 (IGFBP-1) are tightly connected to metabolic changes and complications in patients with diabetes mellitus (DM), and since they mutually interact to form complexes in plasma, we investigated whether and to what extent IGFBP-1/fibrinogen complexes change due to glyco-oxidative processes in DM and whether they participate in fibrin clot formation. These complexes were determined by immunoblotting in plasma samples from healthy adults and patients with DM type 2 (DM2). The influence of glyco-oxidation in vitro on the complexes was also investigated. Amounts of IGFBP-1/fibrinogen complexes in plasma from patients with DM2 were slightly but not significantly lower than in healthy persons. Such complexes in patients’ samples participated in fibrin clot formation to a significantly decreased extent. In vitro experiments with glucose or methylglyoxal (MGO) as reactive agents demonstrated that the complexes underwent glyco-oxidative modification leading to reduced formation and/or stability. Extensively oxidized fibrinogen almost completely lost its ability to bind IGFBP-1. The reduced affinity of fibrinogen for IGFBP-1 accompanying diabetes may potentially shift the equilibrium to liberate more IGFBP-1 (and possibly insulin-like growth factor (IGF)-I) able to activate platelets during coagulation, so contributing to the hypercoagulation state together with other factors. This hypothesis, however, needs further examination.