To study platelet activation as a phenomenon that may precede development of angiopathy in diabetes mellitus, we compared platelet adhesion and thrombus formation in a flow system with blood from insulin-dependent (type I) diabetic subjects with and without macroangiopathy and age- and sex-matched control subjects. Adhesion and thrombus formation on matrix of cultured human endothelial cells (ECM) and adhesion on matrix of human fibroblasts (FBM) were studied after exposure to flowing blood at shear rates of 300 and 1300 s-1 and exposure times of 1, 3, 5, and 10 min (and 20 min in adhesion experiments). Blood was anticoagulated with trisodium citrate (1:10 vol/vol, 110 mM) or low-molecular-weight heparin ([LMWH] 20 U/ml). Endothelial cell cultures were either unstimulated or stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) 16 h before isolating their matrix. Platelet adhesion on ECM and FBM in citrated and LMWH-anticoagulated blood was identical in diabetic patients and control subjects, with comparable increases of adhesion with increasing perfusion times. Platelet aggregate formation on ECM of PMA-stimulated cells with LMWH-anticoagulated blood was similar in diabetic patients, whether macroangiopathy was present, compared with control subjects. Fibrin deposition and fibrinopeptide A generation during perfusion were comparable in diabetic and control subjects. Platelet thromboxane B2 formation after stimulation with arachidonic acid was increased in diabetic patients without macroangiopathy compared with age- and sex-matched control subjects. In the perfusion system, the patterns of platelet adhesion and aggregate formation on extracellular matrix in flowing blood of diabetic patients (with or without macroangiopathy), and healthy age- and sex-matched control subjects followed a similar pattern.(ABSTRACT TRUNCATED AT 250 WORDS)