THE ASSOCIATION OF REDUCED ENDOTHELIUM-DERIVED RELAXING FACTOR-NO PRODUCTION WITH ENDOTHELIAL DAMAGE AND INCREASED IN-VIVO PLATELET ACTIVATION IN PATIENTS WITH DIABETES-MELLITUS

The role of reduced endothelial production of EDRF-NO in the pathogene sis of diabetic angiopathy has received much attention, however, most of the rather conflicting data were gained from animal experiments. Li mited human experience seems to be available in insulin dependent diab etes, calling attention to decreased EDRF-NO production. Hereby the cl inical, as well as laboratory investigation (urinary and serum nitrate /nitrite, lipid peroxidation, glucometabolic parameters, endothelial a nd in vivo platelet activation markers, etc.) of 35 non-insulin depend ent (NIDDM) and 15 insulin dependent diabetics (IDDM) patients are giv en. Urinary and serum nitrate/nitrite concentrations were proven to be reduced in both patients groups. This change was independent of diabe tes duration, presence of macroangiopathy, coronary heart disease and the glucometabolic parameters, however, correlation was registered wit h lipid peroxidation (total antioxidant status). An inverse correlatio n of nitrate/nitrite excretion with endothelial markers (von Willebran d factor, soluble thrombomodulin) was documented in NIDDM, this correl ation was much stronger in IDDM. Moreover, in IDDM patients reduced ni trate/nitrite excretion was strongly associated with elevated plasmati c beta-thromboglobulin levels. The data presented here support to the hypothesis, that EDRF-NO production is reduced in diabetes and this re duction seems to correlate with endothelial damage. In IDDM the decrea sed nitrate/nitrite excretion may also lead to increased in vivo plate let activation, which suggests that the reduced amount of EDRF-NO migh t play a role in the pathogenesis of angiopathy in IDDM. (C) 1997 Else vier Science Ltd.